Clinical Endocrinology News

Doctors have urged caution in linking the weight loss drug tirzepatide to the death of a 58-year-old nurse from Scotland.

Susan McGowan, from North Lanarkshire, took two low-dose injections of tirzepatide (Mounjaro) over the course of about 2 weeks before her death in September. 

BBC News reported that multiple organ failure, septic shock, and pancreatitis were listed on her death certificate as the immediate cause of death, with “the use of prescribed tirzepatide” recorded as a contributing factor.

McGowan worked as a nurse at University Hospital Monklands in Airdrie. A family member said that, apart from carrying a “bit of extra weight,” she had been otherwise healthy and was not taking any other medication.

It is understood that McGowan had sought medical advice before purchasing a prescription for tirzepatide through a registered UK pharmacy. However, days after administering a second injection, she went to A&E at Monklands with severe stomach pain and sickness. She died on September 4.
 

Expert Insights

Commenting to the Science Media Centre (SMC), Amanda Adler, MD, PhD, professor of diabetic medicine and health policy at the University of Oxford, described the nurse’s death as “sad” but said that “whether or not it was related to tirzepatide may be difficult to prove.” While tirzepatide can be associated with uncommon problems such as acute pancreatitis, “one can develop acute pancreatitis for many other reasons as well,” she said. 

Naveed Sattar, MD, PhD, professor of metabolic medicine at the University of Glasgow, noted that data from multiple trials of tirzepatide, involving around 10,000 people living with diabetes or obesity, “do not suggest a higher risk of pancreatitis.” Furthermore, “the data seem to show acceptable safety thus far and a range of benefits including sizable average weight loss (near 20%), strong diabetes prevention, and considerable benefits in people living with sleep apnea,” he told the SMC.
 

Approved Based on Extensive Assessment

Tirzepatide, a GLP-1 receptor agonist, was approved for use as a weight loss aid in the United Kingdom in November last year by the Medicines and Healthcare products Regulatory Agency (MHRA). It lists nausea, diarrhea, and vomiting as the most common side effects, as well as hypoglycemia for patients with diabetes.

Available figures under the Yellow Card scheme up to 19 May 2024 show that there were 208 adverse drug reactions reported about tirzepatide this year, including 31 serious reactions and one suspected death of a man in his 60s.

In a statement, a spokesperson for the drug’s manufacturer, Eli Lilly, said, “Patient safety is Lilly’s top priority. We are committed to continually monitoring, evaluating, and reporting safety information for all Lilly medicines. 

“Mounjaro (tirzepatide) was approved based on extensive assessment of the benefits and risks of the medicine, and we provide information about the benefits and risks of all our medicines to regulators around the world to ensure the latest information is available for prescribers. If anyone is experiencing side effects when taking any Lilly medicine, they should talk to their doctor or other healthcare professional.” 

In October, the NHS submitted plans to the National Institute for Health and Care Excellence (NICE) for a phased rollout of tirzepatide in England that would initially prioritize patients with the greatest clinical need. The first phase would see the drug available to people with a body mass index of more than 40 kg/m² who also suffer from at least three of the main weight-related health problems: hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease.

“Our sincere sympathies are with the family of individual concerned,” said Alison Cave, MHRA Chief Safety Officer.

“Patient safety is our top priority and no medicine would be approved unless it met our expected standards of safety, quality, and effectiveness. Our role is to continually monitor the safety of medicines during their use, such as GLP-1 RAs. We have robust, safety monitoring and surveillance systems in place for all healthcare products.  

“New medicines, such as tirzepatide, are more intensively monitored to ensure that any new safety issues are identified promptly. We strongly encourage the reporting of all suspected reactions to newer medicines, which are denoted by an inverted Black Triangle symbol.

“On the basis of the current evidence the benefits of GLP-1 RAs outweigh the potential risks when used for the licensed indications. The decision to start, continue, or stop treatments should be made jointly by patients and their doctor, based on full consideration of the benefits and risks.” 

She encouraged patients and healthcare professionals to continue reporting suspected side effects to GLP-1 RAs, such as tirzepatide, through the Yellow Card Scheme. “When a safety issue is confirmed, we always act promptly to inform patients and healthcare professionals and take appropriate steps to mitigate any identified risk.”

The Department of Health and Social Care declined to comment. 

Adler disclosed being involved as an unpaid investigator on an Eli Lilly–funded trial for a different drug. Sattar has disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Doctors have urged caution in linking the weight loss drug tirzepatide to the death of a 58-year-old nurse from Scotland.

Susan McGowan, from North Lanarkshire, took two low-dose injections of tirzepatide (Mounjaro) over the course of about 2 weeks before her death in September. 

BBC News reported that multiple organ failure, septic shock, and pancreatitis were listed on her death certificate as the immediate cause of death, with “the use of prescribed tirzepatide” recorded as a contributing factor.

McGowan worked as a nurse at University Hospital Monklands in Airdrie. A family member said that, apart from carrying a “bit of extra weight,” she had been otherwise healthy and was not taking any other medication.

It is understood that McGowan had sought medical advice before purchasing a prescription for tirzepatide through a registered UK pharmacy. However, days after administering a second injection, she went to A&E at Monklands with severe stomach pain and sickness. She died on September 4.
 

Expert Insights

Commenting to the Science Media Centre (SMC), Amanda Adler, MD, PhD, professor of diabetic medicine and health policy at the University of Oxford, described the nurse’s death as “sad” but said that “whether or not it was related to tirzepatide may be difficult to prove.” While tirzepatide can be associated with uncommon problems such as acute pancreatitis, “one can develop acute pancreatitis for many other reasons as well,” she said. 

Naveed Sattar, MD, PhD, professor of metabolic medicine at the University of Glasgow, noted that data from multiple trials of tirzepatide, involving around 10,000 people living with diabetes or obesity, “do not suggest a higher risk of pancreatitis.” Furthermore, “the data seem to show acceptable safety thus far and a range of benefits including sizable average weight loss (near 20%), strong diabetes prevention, and considerable benefits in people living with sleep apnea,” he told the SMC.
 

Approved Based on Extensive Assessment

Tirzepatide, a GLP-1 receptor agonist, was approved for use as a weight loss aid in the United Kingdom in November last year by the Medicines and Healthcare products Regulatory Agency (MHRA). It lists nausea, diarrhea, and vomiting as the most common side effects, as well as hypoglycemia for patients with diabetes.

Available figures under the Yellow Card scheme up to 19 May 2024 show that there were 208 adverse drug reactions reported about tirzepatide this year, including 31 serious reactions and one suspected death of a man in his 60s.

In a statement, a spokesperson for the drug’s manufacturer, Eli Lilly, said, “Patient safety is Lilly’s top priority. We are committed to continually monitoring, evaluating, and reporting safety information for all Lilly medicines. 

“Mounjaro (tirzepatide) was approved based on extensive assessment of the benefits and risks of the medicine, and we provide information about the benefits and risks of all our medicines to regulators around the world to ensure the latest information is available for prescribers. If anyone is experiencing side effects when taking any Lilly medicine, they should talk to their doctor or other healthcare professional.” 

In October, the NHS submitted plans to the National Institute for Health and Care Excellence (NICE) for a phased rollout of tirzepatide in England that would initially prioritize patients with the greatest clinical need. The first phase would see the drug available to people with a body mass index of more than 40 kg/m² who also suffer from at least three of the main weight-related health problems: hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease.

“Our sincere sympathies are with the family of individual concerned,” said Alison Cave, MHRA Chief Safety Officer.

“Patient safety is our top priority and no medicine would be approved unless it met our expected standards of safety, quality, and effectiveness. Our role is to continually monitor the safety of medicines during their use, such as GLP-1 RAs. We have robust, safety monitoring and surveillance systems in place for all healthcare products.  

“New medicines, such as tirzepatide, are more intensively monitored to ensure that any new safety issues are identified promptly. We strongly encourage the reporting of all suspected reactions to newer medicines, which are denoted by an inverted Black Triangle symbol.

“On the basis of the current evidence the benefits of GLP-1 RAs outweigh the potential risks when used for the licensed indications. The decision to start, continue, or stop treatments should be made jointly by patients and their doctor, based on full consideration of the benefits and risks.” 

She encouraged patients and healthcare professionals to continue reporting suspected side effects to GLP-1 RAs, such as tirzepatide, through the Yellow Card Scheme. “When a safety issue is confirmed, we always act promptly to inform patients and healthcare professionals and take appropriate steps to mitigate any identified risk.”

The Department of Health and Social Care declined to comment. 

Adler disclosed being involved as an unpaid investigator on an Eli Lilly–funded trial for a different drug. Sattar has disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Doctors have urged caution in linking the weight loss drug tirzepatide to the death of a 58-year-old nurse from Scotland.

Susan McGowan, from North Lanarkshire, took two low-dose injections of tirzepatide (Mounjaro) over the course of about 2 weeks before her death in September. 

BBC News reported that multiple organ failure, septic shock, and pancreatitis were listed on her death certificate as the immediate cause of death, with “the use of prescribed tirzepatide” recorded as a contributing factor.

McGowan worked as a nurse at University Hospital Monklands in Airdrie. A family member said that, apart from carrying a “bit of extra weight,” she had been otherwise healthy and was not taking any other medication.

It is understood that McGowan had sought medical advice before purchasing a prescription for tirzepatide through a registered UK pharmacy. However, days after administering a second injection, she went to A&E at Monklands with severe stomach pain and sickness. She died on September 4.
 

Expert Insights

Commenting to the Science Media Centre (SMC), Amanda Adler, MD, PhD, professor of diabetic medicine and health policy at the University of Oxford, described the nurse’s death as “sad” but said that “whether or not it was related to tirzepatide may be difficult to prove.” While tirzepatide can be associated with uncommon problems such as acute pancreatitis, “one can develop acute pancreatitis for many other reasons as well,” she said. 

Naveed Sattar, MD, PhD, professor of metabolic medicine at the University of Glasgow, noted that data from multiple trials of tirzepatide, involving around 10,000 people living with diabetes or obesity, “do not suggest a higher risk of pancreatitis.” Furthermore, “the data seem to show acceptable safety thus far and a range of benefits including sizable average weight loss (near 20%), strong diabetes prevention, and considerable benefits in people living with sleep apnea,” he told the SMC.
 

Approved Based on Extensive Assessment

Tirzepatide, a GLP-1 receptor agonist, was approved for use as a weight loss aid in the United Kingdom in November last year by the Medicines and Healthcare products Regulatory Agency (MHRA). It lists nausea, diarrhea, and vomiting as the most common side effects, as well as hypoglycemia for patients with diabetes.

Available figures under the Yellow Card scheme up to 19 May 2024 show that there were 208 adverse drug reactions reported about tirzepatide this year, including 31 serious reactions and one suspected death of a man in his 60s.

In a statement, a spokesperson for the drug’s manufacturer, Eli Lilly, said, “Patient safety is Lilly’s top priority. We are committed to continually monitoring, evaluating, and reporting safety information for all Lilly medicines. 

“Mounjaro (tirzepatide) was approved based on extensive assessment of the benefits and risks of the medicine, and we provide information about the benefits and risks of all our medicines to regulators around the world to ensure the latest information is available for prescribers. If anyone is experiencing side effects when taking any Lilly medicine, they should talk to their doctor or other healthcare professional.” 

In October, the NHS submitted plans to the National Institute for Health and Care Excellence (NICE) for a phased rollout of tirzepatide in England that would initially prioritize patients with the greatest clinical need. The first phase would see the drug available to people with a body mass index of more than 40 kg/m² who also suffer from at least three of the main weight-related health problems: hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease.

“Our sincere sympathies are with the family of individual concerned,” said Alison Cave, MHRA Chief Safety Officer.

“Patient safety is our top priority and no medicine would be approved unless it met our expected standards of safety, quality, and effectiveness. Our role is to continually monitor the safety of medicines during their use, such as GLP-1 RAs. We have robust, safety monitoring and surveillance systems in place for all healthcare products.  

“New medicines, such as tirzepatide, are more intensively monitored to ensure that any new safety issues are identified promptly. We strongly encourage the reporting of all suspected reactions to newer medicines, which are denoted by an inverted Black Triangle symbol.

“On the basis of the current evidence the benefits of GLP-1 RAs outweigh the potential risks when used for the licensed indications. The decision to start, continue, or stop treatments should be made jointly by patients and their doctor, based on full consideration of the benefits and risks.” 

She encouraged patients and healthcare professionals to continue reporting suspected side effects to GLP-1 RAs, such as tirzepatide, through the Yellow Card Scheme. “When a safety issue is confirmed, we always act promptly to inform patients and healthcare professionals and take appropriate steps to mitigate any identified risk.”

The Department of Health and Social Care declined to comment. 

Adler disclosed being involved as an unpaid investigator on an Eli Lilly–funded trial for a different drug. Sattar has disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

The search for a better biomarker than creatine for acute kidney injury (AKI) has been “long and elusive.” However, could researchers be on the right path now?

“The thinking is moving away from trying to find one biomarker that can be used for different types of kidney injury to a recognition that AKI is not just a single disease that a patient has or doesn’t have,” Rob D. Nerenz, PhD, an associate professor in the Department of Pathology and Laboratory Medicine at the Medical College of Wisconsin, Milwaukee, told this news organization. “It’s lots of different diseases that all affect the kidney in different ways.”

AKI is actually a “loose collection” of hepatorenal, cardiorenal, nephrotoxic, and sepsis-associated syndromes, as well as acute interstitial nephritis (AIN), he said. “So the question is not: ‘Is AKI present — yes or no?’ It’s: ‘What kind of AKI is present, and how do I treat it?’ ”
 

‘Mediocre Markers’

AKI affects about 10%-30% of hospitalized patients, according to Nerenz. It’s associated with an increased risk for adverse outcomes, including post-AKI chronic kidney disease and a mortality rate of approximately 24%.

Currently, AKI is defined by a rapid increase in serum creatinine, a decrease in urine output, or both.

“Those are mediocre markers,” Nerenz said, as serum creatinine is not very sensitive to acute change, and the increase is often detected after the therapeutic window of intervention has passed. In addition, “it only tells us that the kidneys are unhappy; it doesn’t say anything about the cause.”

Urine output is limited as a marker because many conditions affect it. “If you’re dehydrated, urine output is going to decrease,” he said. “And in some forms of AKI, urine output actually goes up.”

What’s needed, he said, is a more sensitive biomarker that’s detectable within a shorter timeframe of 2-6 hours following injury.

“Right now, we’re looking at 48 hours before a change becomes apparent, and that’s just too long. Plus, it should be kidney specific. One of the major limitations of the biomarkers that have been evaluated to this point is that, yes, they’re released by the kidney, but they’re also released by other tissue types within the body, and that hinders their effectiveness as a marker.”
 

Neutrophil Gelatinase-Associated Lipocalin (NGAL)

Although research on better biomarkers is ongoing, “there’s also a recognition that some of the protein markers that have been around for a while, if used appropriately, can provide value,” Nerenz said. These include, among others, NGAL.

NGAL works well in pediatric patients without other comorbidities, but it has been less useful in adult patients because it is also released by other cell types. However, recent research suggests it shows promise in patients with both cirrhosis and AKI.

There are three main causes of AKI in cirrhosis, Nerenz explained. The first is prerenal and can be primarily addressed through rehydration.

“When these patients come in, clinicians won’t do anything right away other than provide fluids. If creatinine improves over the 48-hour period of fluid replenishment, then the patient is sent home because there really isn’t extensive damage to the kidneys.”

If improvement isn’t seen after those 48 hours, then it could be one of two things: Hepatorenal syndrome or acute tubular necrosis. Patients with hepatorenal syndrome are candidates for terlipressin, which the Food and Drug Administration (FDA) approved for this indication in 2022 after it displayed notable efficacy in a double-blind study.

“You don’t want to give terlipressin to just anybody because if the issue is not a diminished blood supply to the kidney, it’s not going to help, and comes with some serious side effects, such as respiratory failure,” Nerenz explained. “Having a biomarker that can distinguish between hepatorenal syndrome and acute tubular necrosis really helps clinicians confidently identify which patients are good candidates for this drug. Right now, we’re flying blind to a certain extent, basically using clinical intuition.”

Currently, the determination of NGAL is FDA cleared only for pediatric use. One way hospitals have dealt with that is by making the test in their own labs, using appropriate reagents, validation, and so forth. These tests are then safe for use in adults but haven’t gone through the FDA approval process.

However, the FDA’s recent announcement stating that the agency should oversee lab-developed tests has made this situation unclear, Nerenz said.

“At this point, we don’t know if there’s still an opportunity to take the NGAL test (or any other cleared biomarker) and validate it for use in a different patient population. Many hospital labs simply don’t have the resources to take these tests through the whole FDA approval process.”
 

A New Biomarker for AIN?

Meanwhile, research is also moving forward on a better biomarker for AIN, which is also under the AKI umbrella.

“It’s important to diagnose AIN because it has a very specific treatment,” Dennis G. Moledina, MD, PhD, Yale School of Medicine in New Haven, Connecticut, told this news organization.

“AIN is caused by a bunch of different medications, such as proton pump inhibitors, cancer drugs, nonsteroidal anti-inflammatory drugs, and antibiotics, so when someone has this condition, you have to stop potentially life-saving medications and give unnecessary and potentially toxic immunosuppressive drugs, like prednisone,” he said. “If you get the diagnosis wrong, you’re stopping vital drugs and giving immunosuppression for no reason. And if you miss the diagnosis, AIN can lead to permanent chronic kidney disease.”

“Right now, the only way to diagnose AIN is to do a kidney biopsy, which is risky because it can often lead to significant bleeding,” he said. “Some people can’t undergo a biopsy because they’re on medications that increase the risk of bleeding, and they can’t be stopped.”

Furthermore, he noted, “the longer a patient takes a drug that’s causing AIN without getting a diagnosis, the less the chances of recovery because the longer you let this kidney inflammation go on, the more fibrosis and permanent damage develops. So it is important to diagnose it as early as possible, and that’s again why we have a real need for a noninvasive biomarker that can be tested rapidly.”

Moledina and colleagues have been working on identifying a suitable biomarker for close to 10 years, the latest example of which is their 2023 study validating urinary CXCL9 as just such a marker.

“We’re most excited about CXCL9 because it’s already used to diagnose some other diseases in plasma,” Moledina said. “We think that we can convince labs to test it in urine.”

In an accompanying editorial, Mark Canney, PhD, and colleagues at the University of Ottawa and The Ottawa Hospital in Ontario, Canada, wrote that the CXCL9 study findings “are exciting because they provide a road map of where diagnostics can get to for this common, yet poorly identified and treated, cause of kidney damage. The need for a different approach can be readily identified from the fact that clinicians’ gestalt for diagnosing AIN was almost tantamount to tossing a coin (AUC, 0.57). CXCL9 alone outperformed not only the clinician’s prebiopsy suspicion but also an existing diagnostic model and other candidate biomarkers both in the discovery and external validation cohorts.”

Like NGAL, CXCL9 will have to go through the FDA approval process before it can be used for AIN. Therefore, it may be a few years before it can become routinely available, Moledina said.

Nevertheless, Nerenz added, “I think the next steps for AKI are probably continuing on this path of context-dependent, selective biomarker use. I anticipate that we’ll see ongoing development in this space, just expanding to a wider variety of clinical scenarios.”

Nerenz declared receiving research funding from Abbott Labs for evaluation of an AKI biomarker. Moledina is a co-inventor on a pending patent, “Methods and Systems for Diagnosis of Acute Interstitial Nephritis”; a cofounder of the diagnostics company Predict AIN; and a consultant for Biohaven.

A version of this article first appeared on Medscape.com.

The search for a better biomarker than creatine for acute kidney injury (AKI) has been “long and elusive.” However, could researchers be on the right path now?

“The thinking is moving away from trying to find one biomarker that can be used for different types of kidney injury to a recognition that AKI is not just a single disease that a patient has or doesn’t have,” Rob D. Nerenz, PhD, an associate professor in the Department of Pathology and Laboratory Medicine at the Medical College of Wisconsin, Milwaukee, told this news organization. “It’s lots of different diseases that all affect the kidney in different ways.”

AKI is actually a “loose collection” of hepatorenal, cardiorenal, nephrotoxic, and sepsis-associated syndromes, as well as acute interstitial nephritis (AIN), he said. “So the question is not: ‘Is AKI present — yes or no?’ It’s: ‘What kind of AKI is present, and how do I treat it?’ ”
 

‘Mediocre Markers’

AKI affects about 10%-30% of hospitalized patients, according to Nerenz. It’s associated with an increased risk for adverse outcomes, including post-AKI chronic kidney disease and a mortality rate of approximately 24%.

Currently, AKI is defined by a rapid increase in serum creatinine, a decrease in urine output, or both.

“Those are mediocre markers,” Nerenz said, as serum creatinine is not very sensitive to acute change, and the increase is often detected after the therapeutic window of intervention has passed. In addition, “it only tells us that the kidneys are unhappy; it doesn’t say anything about the cause.”

Urine output is limited as a marker because many conditions affect it. “If you’re dehydrated, urine output is going to decrease,” he said. “And in some forms of AKI, urine output actually goes up.”

What’s needed, he said, is a more sensitive biomarker that’s detectable within a shorter timeframe of 2-6 hours following injury.

“Right now, we’re looking at 48 hours before a change becomes apparent, and that’s just too long. Plus, it should be kidney specific. One of the major limitations of the biomarkers that have been evaluated to this point is that, yes, they’re released by the kidney, but they’re also released by other tissue types within the body, and that hinders their effectiveness as a marker.”
 

Neutrophil Gelatinase-Associated Lipocalin (NGAL)

Although research on better biomarkers is ongoing, “there’s also a recognition that some of the protein markers that have been around for a while, if used appropriately, can provide value,” Nerenz said. These include, among others, NGAL.

NGAL works well in pediatric patients without other comorbidities, but it has been less useful in adult patients because it is also released by other cell types. However, recent research suggests it shows promise in patients with both cirrhosis and AKI.

There are three main causes of AKI in cirrhosis, Nerenz explained. The first is prerenal and can be primarily addressed through rehydration.

“When these patients come in, clinicians won’t do anything right away other than provide fluids. If creatinine improves over the 48-hour period of fluid replenishment, then the patient is sent home because there really isn’t extensive damage to the kidneys.”

If improvement isn’t seen after those 48 hours, then it could be one of two things: Hepatorenal syndrome or acute tubular necrosis. Patients with hepatorenal syndrome are candidates for terlipressin, which the Food and Drug Administration (FDA) approved for this indication in 2022 after it displayed notable efficacy in a double-blind study.

“You don’t want to give terlipressin to just anybody because if the issue is not a diminished blood supply to the kidney, it’s not going to help, and comes with some serious side effects, such as respiratory failure,” Nerenz explained. “Having a biomarker that can distinguish between hepatorenal syndrome and acute tubular necrosis really helps clinicians confidently identify which patients are good candidates for this drug. Right now, we’re flying blind to a certain extent, basically using clinical intuition.”

Currently, the determination of NGAL is FDA cleared only for pediatric use. One way hospitals have dealt with that is by making the test in their own labs, using appropriate reagents, validation, and so forth. These tests are then safe for use in adults but haven’t gone through the FDA approval process.

However, the FDA’s recent announcement stating that the agency should oversee lab-developed tests has made this situation unclear, Nerenz said.

“At this point, we don’t know if there’s still an opportunity to take the NGAL test (or any other cleared biomarker) and validate it for use in a different patient population. Many hospital labs simply don’t have the resources to take these tests through the whole FDA approval process.”
 

A New Biomarker for AIN?

Meanwhile, research is also moving forward on a better biomarker for AIN, which is also under the AKI umbrella.

“It’s important to diagnose AIN because it has a very specific treatment,” Dennis G. Moledina, MD, PhD, Yale School of Medicine in New Haven, Connecticut, told this news organization.

“AIN is caused by a bunch of different medications, such as proton pump inhibitors, cancer drugs, nonsteroidal anti-inflammatory drugs, and antibiotics, so when someone has this condition, you have to stop potentially life-saving medications and give unnecessary and potentially toxic immunosuppressive drugs, like prednisone,” he said. “If you get the diagnosis wrong, you’re stopping vital drugs and giving immunosuppression for no reason. And if you miss the diagnosis, AIN can lead to permanent chronic kidney disease.”

“Right now, the only way to diagnose AIN is to do a kidney biopsy, which is risky because it can often lead to significant bleeding,” he said. “Some people can’t undergo a biopsy because they’re on medications that increase the risk of bleeding, and they can’t be stopped.”

Furthermore, he noted, “the longer a patient takes a drug that’s causing AIN without getting a diagnosis, the less the chances of recovery because the longer you let this kidney inflammation go on, the more fibrosis and permanent damage develops. So it is important to diagnose it as early as possible, and that’s again why we have a real need for a noninvasive biomarker that can be tested rapidly.”

Moledina and colleagues have been working on identifying a suitable biomarker for close to 10 years, the latest example of which is their 2023 study validating urinary CXCL9 as just such a marker.

“We’re most excited about CXCL9 because it’s already used to diagnose some other diseases in plasma,” Moledina said. “We think that we can convince labs to test it in urine.”

In an accompanying editorial, Mark Canney, PhD, and colleagues at the University of Ottawa and The Ottawa Hospital in Ontario, Canada, wrote that the CXCL9 study findings “are exciting because they provide a road map of where diagnostics can get to for this common, yet poorly identified and treated, cause of kidney damage. The need for a different approach can be readily identified from the fact that clinicians’ gestalt for diagnosing AIN was almost tantamount to tossing a coin (AUC, 0.57). CXCL9 alone outperformed not only the clinician’s prebiopsy suspicion but also an existing diagnostic model and other candidate biomarkers both in the discovery and external validation cohorts.”

Like NGAL, CXCL9 will have to go through the FDA approval process before it can be used for AIN. Therefore, it may be a few years before it can become routinely available, Moledina said.

Nevertheless, Nerenz added, “I think the next steps for AKI are probably continuing on this path of context-dependent, selective biomarker use. I anticipate that we’ll see ongoing development in this space, just expanding to a wider variety of clinical scenarios.”

Nerenz declared receiving research funding from Abbott Labs for evaluation of an AKI biomarker. Moledina is a co-inventor on a pending patent, “Methods and Systems for Diagnosis of Acute Interstitial Nephritis”; a cofounder of the diagnostics company Predict AIN; and a consultant for Biohaven.

A version of this article first appeared on Medscape.com.

The search for a better biomarker than creatine for acute kidney injury (AKI) has been “long and elusive.” However, could researchers be on the right path now?

“The thinking is moving away from trying to find one biomarker that can be used for different types of kidney injury to a recognition that AKI is not just a single disease that a patient has or doesn’t have,” Rob D. Nerenz, PhD, an associate professor in the Department of Pathology and Laboratory Medicine at the Medical College of Wisconsin, Milwaukee, told this news organization. “It’s lots of different diseases that all affect the kidney in different ways.”

AKI is actually a “loose collection” of hepatorenal, cardiorenal, nephrotoxic, and sepsis-associated syndromes, as well as acute interstitial nephritis (AIN), he said. “So the question is not: ‘Is AKI present — yes or no?’ It’s: ‘What kind of AKI is present, and how do I treat it?’ ”
 

‘Mediocre Markers’

AKI affects about 10%-30% of hospitalized patients, according to Nerenz. It’s associated with an increased risk for adverse outcomes, including post-AKI chronic kidney disease and a mortality rate of approximately 24%.

Currently, AKI is defined by a rapid increase in serum creatinine, a decrease in urine output, or both.

“Those are mediocre markers,” Nerenz said, as serum creatinine is not very sensitive to acute change, and the increase is often detected after the therapeutic window of intervention has passed. In addition, “it only tells us that the kidneys are unhappy; it doesn’t say anything about the cause.”

Urine output is limited as a marker because many conditions affect it. “If you’re dehydrated, urine output is going to decrease,” he said. “And in some forms of AKI, urine output actually goes up.”

What’s needed, he said, is a more sensitive biomarker that’s detectable within a shorter timeframe of 2-6 hours following injury.

“Right now, we’re looking at 48 hours before a change becomes apparent, and that’s just too long. Plus, it should be kidney specific. One of the major limitations of the biomarkers that have been evaluated to this point is that, yes, they’re released by the kidney, but they’re also released by other tissue types within the body, and that hinders their effectiveness as a marker.”
 

Neutrophil Gelatinase-Associated Lipocalin (NGAL)

Although research on better biomarkers is ongoing, “there’s also a recognition that some of the protein markers that have been around for a while, if used appropriately, can provide value,” Nerenz said. These include, among others, NGAL.

NGAL works well in pediatric patients without other comorbidities, but it has been less useful in adult patients because it is also released by other cell types. However, recent research suggests it shows promise in patients with both cirrhosis and AKI.

There are three main causes of AKI in cirrhosis, Nerenz explained. The first is prerenal and can be primarily addressed through rehydration.

“When these patients come in, clinicians won’t do anything right away other than provide fluids. If creatinine improves over the 48-hour period of fluid replenishment, then the patient is sent home because there really isn’t extensive damage to the kidneys.”

If improvement isn’t seen after those 48 hours, then it could be one of two things: Hepatorenal syndrome or acute tubular necrosis. Patients with hepatorenal syndrome are candidates for terlipressin, which the Food and Drug Administration (FDA) approved for this indication in 2022 after it displayed notable efficacy in a double-blind study.

“You don’t want to give terlipressin to just anybody because if the issue is not a diminished blood supply to the kidney, it’s not going to help, and comes with some serious side effects, such as respiratory failure,” Nerenz explained. “Having a biomarker that can distinguish between hepatorenal syndrome and acute tubular necrosis really helps clinicians confidently identify which patients are good candidates for this drug. Right now, we’re flying blind to a certain extent, basically using clinical intuition.”

Currently, the determination of NGAL is FDA cleared only for pediatric use. One way hospitals have dealt with that is by making the test in their own labs, using appropriate reagents, validation, and so forth. These tests are then safe for use in adults but haven’t gone through the FDA approval process.

However, the FDA’s recent announcement stating that the agency should oversee lab-developed tests has made this situation unclear, Nerenz said.

“At this point, we don’t know if there’s still an opportunity to take the NGAL test (or any other cleared biomarker) and validate it for use in a different patient population. Many hospital labs simply don’t have the resources to take these tests through the whole FDA approval process.”
 

A New Biomarker for AIN?

Meanwhile, research is also moving forward on a better biomarker for AIN, which is also under the AKI umbrella.

“It’s important to diagnose AIN because it has a very specific treatment,” Dennis G. Moledina, MD, PhD, Yale School of Medicine in New Haven, Connecticut, told this news organization.

“AIN is caused by a bunch of different medications, such as proton pump inhibitors, cancer drugs, nonsteroidal anti-inflammatory drugs, and antibiotics, so when someone has this condition, you have to stop potentially life-saving medications and give unnecessary and potentially toxic immunosuppressive drugs, like prednisone,” he said. “If you get the diagnosis wrong, you’re stopping vital drugs and giving immunosuppression for no reason. And if you miss the diagnosis, AIN can lead to permanent chronic kidney disease.”

“Right now, the only way to diagnose AIN is to do a kidney biopsy, which is risky because it can often lead to significant bleeding,” he said. “Some people can’t undergo a biopsy because they’re on medications that increase the risk of bleeding, and they can’t be stopped.”

Furthermore, he noted, “the longer a patient takes a drug that’s causing AIN without getting a diagnosis, the less the chances of recovery because the longer you let this kidney inflammation go on, the more fibrosis and permanent damage develops. So it is important to diagnose it as early as possible, and that’s again why we have a real need for a noninvasive biomarker that can be tested rapidly.”

Moledina and colleagues have been working on identifying a suitable biomarker for close to 10 years, the latest example of which is their 2023 study validating urinary CXCL9 as just such a marker.

“We’re most excited about CXCL9 because it’s already used to diagnose some other diseases in plasma,” Moledina said. “We think that we can convince labs to test it in urine.”

In an accompanying editorial, Mark Canney, PhD, and colleagues at the University of Ottawa and The Ottawa Hospital in Ontario, Canada, wrote that the CXCL9 study findings “are exciting because they provide a road map of where diagnostics can get to for this common, yet poorly identified and treated, cause of kidney damage. The need for a different approach can be readily identified from the fact that clinicians’ gestalt for diagnosing AIN was almost tantamount to tossing a coin (AUC, 0.57). CXCL9 alone outperformed not only the clinician’s prebiopsy suspicion but also an existing diagnostic model and other candidate biomarkers both in the discovery and external validation cohorts.”

Like NGAL, CXCL9 will have to go through the FDA approval process before it can be used for AIN. Therefore, it may be a few years before it can become routinely available, Moledina said.

Nevertheless, Nerenz added, “I think the next steps for AKI are probably continuing on this path of context-dependent, selective biomarker use. I anticipate that we’ll see ongoing development in this space, just expanding to a wider variety of clinical scenarios.”

Nerenz declared receiving research funding from Abbott Labs for evaluation of an AKI biomarker. Moledina is a co-inventor on a pending patent, “Methods and Systems for Diagnosis of Acute Interstitial Nephritis”; a cofounder of the diagnostics company Predict AIN; and a consultant for Biohaven.

A version of this article first appeared on Medscape.com.

“Cortisol” has become a household word, popularized by social media and tagged in videos that garnered nearly 800 million views in 2023. This is linked to the also-trending term “moon face,” which TikTok influencers and others have suggested is caused by high cortisol levels and, conversely, can be reduced through stress reduction.

Although it’s true that cortisol is a hormone associated with stress, elevated stress levels are unlikely, by themselves, to cause the rounded facial features associated with “moon face.”

“When we hear the term ‘moon face,’ we’re typically referring to Cushing syndrome [CS] or treatment with prolonged high-dose glucocorticoids,” said Anat Ben-Shlomo, MD, co-director of the Multidisciplinary Adrenal Program, Pituitary Center, Division of Endocrinology, Diabetes and Metabolism at Cedars-Sinai Medical Center, Los Angeles. Medscape Medical News previously discussed moon face in an article detailing how to diagnose CS.

Ben-Shlomo noted that the labels “moon face” and “moon facies” should be avoided for their potentially derogatory, unprofessional-sounding connotations, and that the preferred terms are “rounded face” or “round plethoric face.”

There are several disorders that can be associated with facial roundness, not all of which relate to elevated cortisol.

“It’s important for clinicians to be able distinguish between presentations due to other pathophysiologies, identify the unique constellation of Cushing-associated signs and symptoms, engage in a differential diagnosis, and treat whatever the condition is appropriately,” Katherine Sherif, MD, professor and vice chair of academic affairs, Department of Medicine, Thomas Jefferson University, Philadelphia, said in an interview.
 

The Unique Presentation of CS

CS results from “prolonged elevation” in plasma cortisol levels caused by either exogenous steroid use or excess endogenous steroid production.

“The shape of the face isn’t the only feature associated with CS,” Ben-Shlomo said. “There’s central obesity, particularly in the neck, supraclavicular area, chest, and abdomen. You sometimes see a posterior cervical thoracic fat pad, colloquially — but unprofessionally — called a ‘cervical hump.’ Simultaneously, the arms and legs are getting thinner.” The development of a round, plethoric face is common in long-standing significant CS, and a reddening of the skin can appear.

Additional symptoms include hirsutism and acne. “These can also be seen in other conditions, such as PCOS [polycystic ovary syndrome] but, combined with the other facial features, are more suggestive of CS,” Ben-Shlomo said.

Deep, wide purple striae appear in the trunk, breast, upper arms, and thighs, but not in the face, Ben-Shlomo advised. These appear as the fragile, thinning under-skin breaks when the patient gains weight.

Additional metabolic issues that can occur comorbidly include insulin resistance and diabetes, hypertension, osteoporosis, dyslipidemia, ecchymoses, increased susceptibility to infections, mood changes, cognitive dysfunction, low libido, infertility, weakness of muscles in the shoulders and thighs, episodes of bleeding and/or clotting, and an increased risk for heart attacks and strokes, Ben-Shlomo said.

“Not everyone presents with full-blown disease, but if you see any of these symptoms, be suspicious of CS and conduct a biochemical evaluation.” Three screening tests to use as a starting point are recommended by the Pituitary Society’s updated Consensus on Diagnosis and Management of Cushing’s Disease. The tests should be repeated to account for intra-patient variability. If two or all three tests are positive, clinicians should be suspicious of CS and move to additional testing to identify the underlying cause, Ben-Shlomo said.
 

‘Subclinical’ CS

Ben-Shlomo highlighted a condition called minimal autonomous cortisol secretion (formerly “subclinical CS”). “This condition is found when a person has an adrenal nodule that produces cortisol in excess, however not to levels observed in CS. An abnormal finding on the overnight 1-mg low-dose dexamethasone suppression test (LDDST) will identify this disorder, showing mildly unsuppressed morning cortisol level, while all other tests will be within normal range.”

She described minimal autonomous cortisol secretion as a form of “smoldering CS,” which has become more commonly diagnosed. “The condition needs to be treated because the patient can develop insulin resistance, metabolic syndrome, and osteoporosis over time.”

Once a cause has been determined, the optimal course of action is to take a multidisciplinary approach because CS affects multiple systems.
 

‘Pseudo-Cushing Syndrome’

A variety of abnormalities of the hypothalamus-pituitary adrenal (HPA) axis can be associated with hypercortisolemia and a rounder facial appearance but aren’t actually CS, Ben-Shlomo said.

Often called “pseudo-Cushing syndrome,” these conditions have recently been renamed “non-neoplastic hypercortisolism” or “physiologic non-neoplastic endogenous hypercortisolism.” They share some clinical and biochemical features of CS, but the hypercortisolemia is usually secondary to other factors. They increase the secretion of hypothalamic corticotropin-releasing hormone, which stimulates adrenocorticotropic hormone (ACTH) and adrenal cortisol secretion.
 

Identifying PCOS

PCOS is often associated with central obesity, Sherif noted, but not all women with PCOS have overweight or a central distribution of fat.

“Ask about menstrual periods and whether they come monthly,” Sherif advised. “If women using hormonal contraception say they have a regular cycle, ask if their cycle was regular prior to starting contraception. So many women with PCOS are undiagnosed because they started contraception in their teens to ‘regulate their periods’ and never realized they had PCOS.”

Additional symptoms of PCOS and its impact are found in the figure below.

 

Medscape

PCOS is diagnosed when two of the following three Rotterdam criteria are met, and other diagnoses are excluded: 
 

• Irregular menstrual cycles
• Clinical hyperandrogenism or biochemical hyperandrogenism
• Polycystic ovarian morphology on transvaginal ultrasonography or high anti-mullerian hormone (applicable only if patient is ≥ 8 years from menarche)

If PCOS is suspected, further tests can be conducted to confirm or rule out the diagnosis.
 

Alcohol Abuse: Alcohol abuse stimulates hypothalamic corticotropin-releasing hormone, leading to increased ACTH levels. It’s associated with a higher fasting cortisol level, particularly at 8:30 AM or so, and attributable to impaired cortisol clearance due to alcohol-related hepatic dysfunction. The LDDST will show abnormal cortisol suppression.

Sherif advised asking patients about alcohol use, recommending treatment for alcohol use disorder, and repeating clinical and biochemical workup after patients have discontinued alcohol consumption for ≥ 1 month.
 

Eating Disorders Mimicking CS: Eating disorders, particularly anorexia nervosa, are associated with endocrine abnormalities, amenorrhea, impaired body temperature regulation, and hypercortisolism, likely due to chronic fasting-related stress. Dysregulation of the HPA axis may linger, even after weight recovery.

It’s unlikely that patients with anorexia will display the “rounded face” associated with hypercortisolism, but some research suggests that anorexia can result in a disproportionate accumulation of central adiposity after recovery from the illness.
 

Neuropsychiatric Disorders: Major depressive disorder (MDD) is associated with HPA axis hyperactivity, with 20%-30% of patients with MDD showing hypercortisolemia. The post-awakening cortisol surge is more pronounced in those with MDD, and about half of patients with MDD also have high evening cortisol levels, suggesting disrupted diurnal cortisol rhythms.

Some patients with MDD have greater resistance to the feedback action of glucocorticoids on HPA axis activity, with weaker sensitivity often restored by effective pharmacotherapy of the depressive condition. Neuropsychiatric disorders are also associated with reduced activity of cortisol-deactivating enzymes. Posttraumatic stress disorder and anxiety are similarly associated with hypercortisolemia.

Addressing neuropsychiatric conditions with appropriate pharmacotherapy and psychotherapy can restore cortisol levels to normal proportions.
 

Diabetes, Obesity, and Metabolic Syndrome: Diabetes, obesity, and metabolic syndrome can occur comorbidly with CS, and many patients with these conditions may display both a rounder face, some central adiposity, and hypercortisolemia. For example, obesity is often related to a hyperresponsive HPA axis, with elevated cortisol secretion but normal-to-low circulatory concentrations.

Obesity is associated with increased cortisol reactivity after acute physical and/or psychosocial stressors but preserved pituitary sensitivity to feedback inhibition by the LDDST. When these conditions are appropriately managed with pharmacotherapy and lifestyle changes, cortisol levels should normalize, according to the experts.
 

Hypothyroidism: Hypothyroidism— Hashimoto disease as well as the subclinical variety — can be associated with weight gain, which may take the form of central obesity. Some research suggests a bidirectional relationship between hypothyroidism and obesity.

“Years ago, we didn’t conduct thyroid tests very often but now they’re easy to do, so we usually catch people with hypothyroidism at the beginning of the condition,” Sherif said. “If the patient’s thyroid hasn’t been checked in a year or so, thyroid hormone testing should be conducted.”

Thyroid disease can easily be managed with the administration of thyroid hormones.
 

Obstructive Sleep Apnea (OSA): OSA has an impact on HPA axis activation, especially when accompanied by obesity and hypertension. A meta-analysis of 22 studies, encompassing over 600 participants, found that continuous positive airway pressure treatment in patients with OSA reduced cortisol levels as well as blood pressure.

Treatment With Exogenous Corticosteroids: Oral corticosteroid treatment is a cornerstone of therapy in transplant, rheumatic, and autoimmune diseases. The impact of chronic exposure to exogenous glucocorticoids is similar to that with endogenous glucocorticoids.

Sherif said corticosteroid treatment can cause facial roundness in as little as 2 weeks and is characteristic in people taking these agents for longer periods. Although the effects are most pronounced with oral agents, systemic effects can be associated with inhaled corticosteroids as well.

Finding alternative anti-inflammatory treatments is advisable, if possible. The co-administration of metformin might lead to improvements in both the metabolic profile and the clinical outcomes of patients receiving glucocorticoids for inflammatory conditions.
 

Educating Patients: “There’s much we still don’t know about hypercortisolemia and CS, including the reasons for its impact on metabolic derangement and for the accumulation of fat in particular adipose patterns,” Ben-Shlomo said. “But experienced endocrinologists do know relatively well how to diagnose the condition, distinguish it from other conditions presenting with central obesity or a rounder face, and treat it.”

Given the casual use of the terms “moon face” and “extra cortisol” on social media, it’s important for physicians to educate patients about what elevated cortisol does and doesn’t do, and design treatment strategies accordingly.

Neither Ben-Shlomo nor Sherif reported having any disclosures.

A version of this article appeared on Medscape.com.

“Cortisol” has become a household word, popularized by social media and tagged in videos that garnered nearly 800 million views in 2023. This is linked to the also-trending term “moon face,” which TikTok influencers and others have suggested is caused by high cortisol levels and, conversely, can be reduced through stress reduction.

Although it’s true that cortisol is a hormone associated with stress, elevated stress levels are unlikely, by themselves, to cause the rounded facial features associated with “moon face.”

“When we hear the term ‘moon face,’ we’re typically referring to Cushing syndrome [CS] or treatment with prolonged high-dose glucocorticoids,” said Anat Ben-Shlomo, MD, co-director of the Multidisciplinary Adrenal Program, Pituitary Center, Division of Endocrinology, Diabetes and Metabolism at Cedars-Sinai Medical Center, Los Angeles. Medscape Medical News previously discussed moon face in an article detailing how to diagnose CS.

Ben-Shlomo noted that the labels “moon face” and “moon facies” should be avoided for their potentially derogatory, unprofessional-sounding connotations, and that the preferred terms are “rounded face” or “round plethoric face.”

There are several disorders that can be associated with facial roundness, not all of which relate to elevated cortisol.

“It’s important for clinicians to be able distinguish between presentations due to other pathophysiologies, identify the unique constellation of Cushing-associated signs and symptoms, engage in a differential diagnosis, and treat whatever the condition is appropriately,” Katherine Sherif, MD, professor and vice chair of academic affairs, Department of Medicine, Thomas Jefferson University, Philadelphia, said in an interview.
 

The Unique Presentation of CS

CS results from “prolonged elevation” in plasma cortisol levels caused by either exogenous steroid use or excess endogenous steroid production.

“The shape of the face isn’t the only feature associated with CS,” Ben-Shlomo said. “There’s central obesity, particularly in the neck, supraclavicular area, chest, and abdomen. You sometimes see a posterior cervical thoracic fat pad, colloquially — but unprofessionally — called a ‘cervical hump.’ Simultaneously, the arms and legs are getting thinner.” The development of a round, plethoric face is common in long-standing significant CS, and a reddening of the skin can appear.

Additional symptoms include hirsutism and acne. “These can also be seen in other conditions, such as PCOS [polycystic ovary syndrome] but, combined with the other facial features, are more suggestive of CS,” Ben-Shlomo said.

Deep, wide purple striae appear in the trunk, breast, upper arms, and thighs, but not in the face, Ben-Shlomo advised. These appear as the fragile, thinning under-skin breaks when the patient gains weight.

Additional metabolic issues that can occur comorbidly include insulin resistance and diabetes, hypertension, osteoporosis, dyslipidemia, ecchymoses, increased susceptibility to infections, mood changes, cognitive dysfunction, low libido, infertility, weakness of muscles in the shoulders and thighs, episodes of bleeding and/or clotting, and an increased risk for heart attacks and strokes, Ben-Shlomo said.

“Not everyone presents with full-blown disease, but if you see any of these symptoms, be suspicious of CS and conduct a biochemical evaluation.” Three screening tests to use as a starting point are recommended by the Pituitary Society’s updated Consensus on Diagnosis and Management of Cushing’s Disease. The tests should be repeated to account for intra-patient variability. If two or all three tests are positive, clinicians should be suspicious of CS and move to additional testing to identify the underlying cause, Ben-Shlomo said.
 

‘Subclinical’ CS

Ben-Shlomo highlighted a condition called minimal autonomous cortisol secretion (formerly “subclinical CS”). “This condition is found when a person has an adrenal nodule that produces cortisol in excess, however not to levels observed in CS. An abnormal finding on the overnight 1-mg low-dose dexamethasone suppression test (LDDST) will identify this disorder, showing mildly unsuppressed morning cortisol level, while all other tests will be within normal range.”

She described minimal autonomous cortisol secretion as a form of “smoldering CS,” which has become more commonly diagnosed. “The condition needs to be treated because the patient can develop insulin resistance, metabolic syndrome, and osteoporosis over time.”

Once a cause has been determined, the optimal course of action is to take a multidisciplinary approach because CS affects multiple systems.
 

‘Pseudo-Cushing Syndrome’

A variety of abnormalities of the hypothalamus-pituitary adrenal (HPA) axis can be associated with hypercortisolemia and a rounder facial appearance but aren’t actually CS, Ben-Shlomo said.

Often called “pseudo-Cushing syndrome,” these conditions have recently been renamed “non-neoplastic hypercortisolism” or “physiologic non-neoplastic endogenous hypercortisolism.” They share some clinical and biochemical features of CS, but the hypercortisolemia is usually secondary to other factors. They increase the secretion of hypothalamic corticotropin-releasing hormone, which stimulates adrenocorticotropic hormone (ACTH) and adrenal cortisol secretion.
 

Identifying PCOS

PCOS is often associated with central obesity, Sherif noted, but not all women with PCOS have overweight or a central distribution of fat.

“Ask about menstrual periods and whether they come monthly,” Sherif advised. “If women using hormonal contraception say they have a regular cycle, ask if their cycle was regular prior to starting contraception. So many women with PCOS are undiagnosed because they started contraception in their teens to ‘regulate their periods’ and never realized they had PCOS.”

Additional symptoms of PCOS and its impact are found in the figure below.

 

Medscape

PCOS is diagnosed when two of the following three Rotterdam criteria are met, and other diagnoses are excluded: 
 

• Irregular menstrual cycles
• Clinical hyperandrogenism or biochemical hyperandrogenism
• Polycystic ovarian morphology on transvaginal ultrasonography or high anti-mullerian hormone (applicable only if patient is ≥ 8 years from menarche)

If PCOS is suspected, further tests can be conducted to confirm or rule out the diagnosis.
 

Alcohol Abuse: Alcohol abuse stimulates hypothalamic corticotropin-releasing hormone, leading to increased ACTH levels. It’s associated with a higher fasting cortisol level, particularly at 8:30 AM or so, and attributable to impaired cortisol clearance due to alcohol-related hepatic dysfunction. The LDDST will show abnormal cortisol suppression.

Sherif advised asking patients about alcohol use, recommending treatment for alcohol use disorder, and repeating clinical and biochemical workup after patients have discontinued alcohol consumption for ≥ 1 month.
 

Eating Disorders Mimicking CS: Eating disorders, particularly anorexia nervosa, are associated with endocrine abnormalities, amenorrhea, impaired body temperature regulation, and hypercortisolism, likely due to chronic fasting-related stress. Dysregulation of the HPA axis may linger, even after weight recovery.

It’s unlikely that patients with anorexia will display the “rounded face” associated with hypercortisolism, but some research suggests that anorexia can result in a disproportionate accumulation of central adiposity after recovery from the illness.
 

Neuropsychiatric Disorders: Major depressive disorder (MDD) is associated with HPA axis hyperactivity, with 20%-30% of patients with MDD showing hypercortisolemia. The post-awakening cortisol surge is more pronounced in those with MDD, and about half of patients with MDD also have high evening cortisol levels, suggesting disrupted diurnal cortisol rhythms.

Some patients with MDD have greater resistance to the feedback action of glucocorticoids on HPA axis activity, with weaker sensitivity often restored by effective pharmacotherapy of the depressive condition. Neuropsychiatric disorders are also associated with reduced activity of cortisol-deactivating enzymes. Posttraumatic stress disorder and anxiety are similarly associated with hypercortisolemia.

Addressing neuropsychiatric conditions with appropriate pharmacotherapy and psychotherapy can restore cortisol levels to normal proportions.
 

Diabetes, Obesity, and Metabolic Syndrome: Diabetes, obesity, and metabolic syndrome can occur comorbidly with CS, and many patients with these conditions may display both a rounder face, some central adiposity, and hypercortisolemia. For example, obesity is often related to a hyperresponsive HPA axis, with elevated cortisol secretion but normal-to-low circulatory concentrations.

Obesity is associated with increased cortisol reactivity after acute physical and/or psychosocial stressors but preserved pituitary sensitivity to feedback inhibition by the LDDST. When these conditions are appropriately managed with pharmacotherapy and lifestyle changes, cortisol levels should normalize, according to the experts.
 

Hypothyroidism: Hypothyroidism— Hashimoto disease as well as the subclinical variety — can be associated with weight gain, which may take the form of central obesity. Some research suggests a bidirectional relationship between hypothyroidism and obesity.

“Years ago, we didn’t conduct thyroid tests very often but now they’re easy to do, so we usually catch people with hypothyroidism at the beginning of the condition,” Sherif said. “If the patient’s thyroid hasn’t been checked in a year or so, thyroid hormone testing should be conducted.”

Thyroid disease can easily be managed with the administration of thyroid hormones.
 

Obstructive Sleep Apnea (OSA): OSA has an impact on HPA axis activation, especially when accompanied by obesity and hypertension. A meta-analysis of 22 studies, encompassing over 600 participants, found that continuous positive airway pressure treatment in patients with OSA reduced cortisol levels as well as blood pressure.

Treatment With Exogenous Corticosteroids: Oral corticosteroid treatment is a cornerstone of therapy in transplant, rheumatic, and autoimmune diseases. The impact of chronic exposure to exogenous glucocorticoids is similar to that with endogenous glucocorticoids.

Sherif said corticosteroid treatment can cause facial roundness in as little as 2 weeks and is characteristic in people taking these agents for longer periods. Although the effects are most pronounced with oral agents, systemic effects can be associated with inhaled corticosteroids as well.

Finding alternative anti-inflammatory treatments is advisable, if possible. The co-administration of metformin might lead to improvements in both the metabolic profile and the clinical outcomes of patients receiving glucocorticoids for inflammatory conditions.
 

Educating Patients: “There’s much we still don’t know about hypercortisolemia and CS, including the reasons for its impact on metabolic derangement and for the accumulation of fat in particular adipose patterns,” Ben-Shlomo said. “But experienced endocrinologists do know relatively well how to diagnose the condition, distinguish it from other conditions presenting with central obesity or a rounder face, and treat it.”

Given the casual use of the terms “moon face” and “extra cortisol” on social media, it’s important for physicians to educate patients about what elevated cortisol does and doesn’t do, and design treatment strategies accordingly.

Neither Ben-Shlomo nor Sherif reported having any disclosures.

A version of this article appeared on Medscape.com.

“Cortisol” has become a household word, popularized by social media and tagged in videos that garnered nearly 800 million views in 2023. This is linked to the also-trending term “moon face,” which TikTok influencers and others have suggested is caused by high cortisol levels and, conversely, can be reduced through stress reduction.

Although it’s true that cortisol is a hormone associated with stress, elevated stress levels are unlikely, by themselves, to cause the rounded facial features associated with “moon face.”

“When we hear the term ‘moon face,’ we’re typically referring to Cushing syndrome [CS] or treatment with prolonged high-dose glucocorticoids,” said Anat Ben-Shlomo, MD, co-director of the Multidisciplinary Adrenal Program, Pituitary Center, Division of Endocrinology, Diabetes and Metabolism at Cedars-Sinai Medical Center, Los Angeles. Medscape Medical News previously discussed moon face in an article detailing how to diagnose CS.

Ben-Shlomo noted that the labels “moon face” and “moon facies” should be avoided for their potentially derogatory, unprofessional-sounding connotations, and that the preferred terms are “rounded face” or “round plethoric face.”

There are several disorders that can be associated with facial roundness, not all of which relate to elevated cortisol.

“It’s important for clinicians to be able distinguish between presentations due to other pathophysiologies, identify the unique constellation of Cushing-associated signs and symptoms, engage in a differential diagnosis, and treat whatever the condition is appropriately,” Katherine Sherif, MD, professor and vice chair of academic affairs, Department of Medicine, Thomas Jefferson University, Philadelphia, said in an interview.
 

The Unique Presentation of CS

CS results from “prolonged elevation” in plasma cortisol levels caused by either exogenous steroid use or excess endogenous steroid production.

“The shape of the face isn’t the only feature associated with CS,” Ben-Shlomo said. “There’s central obesity, particularly in the neck, supraclavicular area, chest, and abdomen. You sometimes see a posterior cervical thoracic fat pad, colloquially — but unprofessionally — called a ‘cervical hump.’ Simultaneously, the arms and legs are getting thinner.” The development of a round, plethoric face is common in long-standing significant CS, and a reddening of the skin can appear.

Additional symptoms include hirsutism and acne. “These can also be seen in other conditions, such as PCOS [polycystic ovary syndrome] but, combined with the other facial features, are more suggestive of CS,” Ben-Shlomo said.

Deep, wide purple striae appear in the trunk, breast, upper arms, and thighs, but not in the face, Ben-Shlomo advised. These appear as the fragile, thinning under-skin breaks when the patient gains weight.

Additional metabolic issues that can occur comorbidly include insulin resistance and diabetes, hypertension, osteoporosis, dyslipidemia, ecchymoses, increased susceptibility to infections, mood changes, cognitive dysfunction, low libido, infertility, weakness of muscles in the shoulders and thighs, episodes of bleeding and/or clotting, and an increased risk for heart attacks and strokes, Ben-Shlomo said.

“Not everyone presents with full-blown disease, but if you see any of these symptoms, be suspicious of CS and conduct a biochemical evaluation.” Three screening tests to use as a starting point are recommended by the Pituitary Society’s updated Consensus on Diagnosis and Management of Cushing’s Disease. The tests should be repeated to account for intra-patient variability. If two or all three tests are positive, clinicians should be suspicious of CS and move to additional testing to identify the underlying cause, Ben-Shlomo said.
 

‘Subclinical’ CS

Ben-Shlomo highlighted a condition called minimal autonomous cortisol secretion (formerly “subclinical CS”). “This condition is found when a person has an adrenal nodule that produces cortisol in excess, however not to levels observed in CS. An abnormal finding on the overnight 1-mg low-dose dexamethasone suppression test (LDDST) will identify this disorder, showing mildly unsuppressed morning cortisol level, while all other tests will be within normal range.”

She described minimal autonomous cortisol secretion as a form of “smoldering CS,” which has become more commonly diagnosed. “The condition needs to be treated because the patient can develop insulin resistance, metabolic syndrome, and osteoporosis over time.”

Once a cause has been determined, the optimal course of action is to take a multidisciplinary approach because CS affects multiple systems.
 

‘Pseudo-Cushing Syndrome’

A variety of abnormalities of the hypothalamus-pituitary adrenal (HPA) axis can be associated with hypercortisolemia and a rounder facial appearance but aren’t actually CS, Ben-Shlomo said.

Often called “pseudo-Cushing syndrome,” these conditions have recently been renamed “non-neoplastic hypercortisolism” or “physiologic non-neoplastic endogenous hypercortisolism.” They share some clinical and biochemical features of CS, but the hypercortisolemia is usually secondary to other factors. They increase the secretion of hypothalamic corticotropin-releasing hormone, which stimulates adrenocorticotropic hormone (ACTH) and adrenal cortisol secretion.
 

Identifying PCOS

PCOS is often associated with central obesity, Sherif noted, but not all women with PCOS have overweight or a central distribution of fat.

“Ask about menstrual periods and whether they come monthly,” Sherif advised. “If women using hormonal contraception say they have a regular cycle, ask if their cycle was regular prior to starting contraception. So many women with PCOS are undiagnosed because they started contraception in their teens to ‘regulate their periods’ and never realized they had PCOS.”

Additional symptoms of PCOS and its impact are found in the figure below.

 

Medscape

PCOS is diagnosed when two of the following three Rotterdam criteria are met, and other diagnoses are excluded: 
 

• Irregular menstrual cycles
• Clinical hyperandrogenism or biochemical hyperandrogenism
• Polycystic ovarian morphology on transvaginal ultrasonography or high anti-mullerian hormone (applicable only if patient is ≥ 8 years from menarche)

If PCOS is suspected, further tests can be conducted to confirm or rule out the diagnosis.
 

Alcohol Abuse: Alcohol abuse stimulates hypothalamic corticotropin-releasing hormone, leading to increased ACTH levels. It’s associated with a higher fasting cortisol level, particularly at 8:30 AM or so, and attributable to impaired cortisol clearance due to alcohol-related hepatic dysfunction. The LDDST will show abnormal cortisol suppression.

Sherif advised asking patients about alcohol use, recommending treatment for alcohol use disorder, and repeating clinical and biochemical workup after patients have discontinued alcohol consumption for ≥ 1 month.
 

Eating Disorders Mimicking CS: Eating disorders, particularly anorexia nervosa, are associated with endocrine abnormalities, amenorrhea, impaired body temperature regulation, and hypercortisolism, likely due to chronic fasting-related stress. Dysregulation of the HPA axis may linger, even after weight recovery.

It’s unlikely that patients with anorexia will display the “rounded face” associated with hypercortisolism, but some research suggests that anorexia can result in a disproportionate accumulation of central adiposity after recovery from the illness.
 

Neuropsychiatric Disorders: Major depressive disorder (MDD) is associated with HPA axis hyperactivity, with 20%-30% of patients with MDD showing hypercortisolemia. The post-awakening cortisol surge is more pronounced in those with MDD, and about half of patients with MDD also have high evening cortisol levels, suggesting disrupted diurnal cortisol rhythms.

Some patients with MDD have greater resistance to the feedback action of glucocorticoids on HPA axis activity, with weaker sensitivity often restored by effective pharmacotherapy of the depressive condition. Neuropsychiatric disorders are also associated with reduced activity of cortisol-deactivating enzymes. Posttraumatic stress disorder and anxiety are similarly associated with hypercortisolemia.

Addressing neuropsychiatric conditions with appropriate pharmacotherapy and psychotherapy can restore cortisol levels to normal proportions.
 

Diabetes, Obesity, and Metabolic Syndrome: Diabetes, obesity, and metabolic syndrome can occur comorbidly with CS, and many patients with these conditions may display both a rounder face, some central adiposity, and hypercortisolemia. For example, obesity is often related to a hyperresponsive HPA axis, with elevated cortisol secretion but normal-to-low circulatory concentrations.

Obesity is associated with increased cortisol reactivity after acute physical and/or psychosocial stressors but preserved pituitary sensitivity to feedback inhibition by the LDDST. When these conditions are appropriately managed with pharmacotherapy and lifestyle changes, cortisol levels should normalize, according to the experts.
 

Hypothyroidism: Hypothyroidism— Hashimoto disease as well as the subclinical variety — can be associated with weight gain, which may take the form of central obesity. Some research suggests a bidirectional relationship between hypothyroidism and obesity.

“Years ago, we didn’t conduct thyroid tests very often but now they’re easy to do, so we usually catch people with hypothyroidism at the beginning of the condition,” Sherif said. “If the patient’s thyroid hasn’t been checked in a year or so, thyroid hormone testing should be conducted.”

Thyroid disease can easily be managed with the administration of thyroid hormones.
 

Obstructive Sleep Apnea (OSA): OSA has an impact on HPA axis activation, especially when accompanied by obesity and hypertension. A meta-analysis of 22 studies, encompassing over 600 participants, found that continuous positive airway pressure treatment in patients with OSA reduced cortisol levels as well as blood pressure.

Treatment With Exogenous Corticosteroids: Oral corticosteroid treatment is a cornerstone of therapy in transplant, rheumatic, and autoimmune diseases. The impact of chronic exposure to exogenous glucocorticoids is similar to that with endogenous glucocorticoids.

Sherif said corticosteroid treatment can cause facial roundness in as little as 2 weeks and is characteristic in people taking these agents for longer periods. Although the effects are most pronounced with oral agents, systemic effects can be associated with inhaled corticosteroids as well.

Finding alternative anti-inflammatory treatments is advisable, if possible. The co-administration of metformin might lead to improvements in both the metabolic profile and the clinical outcomes of patients receiving glucocorticoids for inflammatory conditions.
 

Educating Patients: “There’s much we still don’t know about hypercortisolemia and CS, including the reasons for its impact on metabolic derangement and for the accumulation of fat in particular adipose patterns,” Ben-Shlomo said. “But experienced endocrinologists do know relatively well how to diagnose the condition, distinguish it from other conditions presenting with central obesity or a rounder face, and treat it.”

Given the casual use of the terms “moon face” and “extra cortisol” on social media, it’s important for physicians to educate patients about what elevated cortisol does and doesn’t do, and design treatment strategies accordingly.

Neither Ben-Shlomo nor Sherif reported having any disclosures.

A version of this article appeared on Medscape.com.

CHICAGO — A preview of much-anticipated updates to guidelines on managing thyroid disease in pregnancy shows key changes to recommendations in the evolving field, ranging from consideration of the chance of spontaneous normalization of thyroid levels during pregnancy to a heightened emphasis on shared decision-making and the nuances can factor into personalized treatment.

The guidelines, expected to be published in early 2025, have not been updated since 2017, and with substantial advances and evidence from countless studies since then, the new guidelines were developed with a goal to start afresh, said ATA Thyroid and Pregnancy Guidelines Task Force cochair Tim IM Korevaar, MD, PhD, in presenting the final draft guidelines at the American Thyroid Association (ATA) 2024 Meeting.

“Obviously, we’re not going to ignore the 2017 guidelines, which have been a very good resource for us so far, but we really wanted to start from scratch and follow a ‘blank canvas’ approach in optimizing the evidence,” said Korevaar, an endocrinologist and obstetric internist with the Division of Pharmacology and Vascular Medicine & Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

The guidelines, developed through a collaborative effort involving a wide variety of related medical societies, involved 14 systematic literature reviews. While the pregnancy issues covered by the guidelines is extensive, key highlights include:
 

Management in Preconception

Beginning with preconception, a key change in the guidelines will be that patients with euthyroid thyroid peroxidase (TPO) antibodies, which can be indicative of thyroid dysfunction, routine treatment with levothyroxine is not recommended, based on new evidence from randomized trials of high-risk patients showing no clear benefit from the treatment. 

“In these trials, and across analyses, there was absolutely no beneficial effect of levothyroxine in these patients [with euthyroid TPO antibody positivity],” he said.

With evidence showing, however, that TPO antibody positivity can lead to subclinical or overt hypothyroidism within 1 or 2 years, the guidelines will recommend that TPO antibody–positive patients do have thyroid stimulating hormone (TSH) levels tested every 3-6 months until pregnancy, and existing recommendations to test during pregnancy among those patients remain in place, Korevaar reported.

In terms of preconception subclinical hypothyroidism, the guidelines will emphasize the existing recommendation “to always strive to reassess” thyroid levels, and if subclinical hypothyroidism does persist, to treat with low-dose levothyroxine.
 

During Pregnancy

During pregnancy, the new proposed recommendations will reflect the important change that three key risk factors, including age over 30 years, having at least two prior pregnancies, and morbid obesity (body mass index [BMI] at least 40 kg/m²), previously considered a risk for thyroid dysfunction in pregnancy, should not, on their own, suggest the need for thyroid testing, based on low evidence of an increased risk in pregnancy.

Research on the issue includes a recent study from Korevaar’s team showing these factors to in fact have low predictability of thyroid dysfunction.

“We deemed that these risk differences weren’t really clinically meaningful (in predicting risk), and so we have removed to maternal age, BMI, and parity as risk factors for thyroid testing indications in pregnancy,” Korevaar said.

Factors considered a risk, resulting in recommended testing at presentation include a history of subclinical or clinical hypo- or hyperthyroidism, postpartum thyroiditis, known thyroid antibody positivity, symptoms of thyroid dysfunction or goiter, and other factors. 
 

Treatment for Subclinical Hypothyroidism in Pregnancy

Whereas current guidelines recommend TPO antibody status in determining when to consider treatment for subclinical hypothyroidism, the new proposed guideline will instead recommend treatment based on the timing of the diagnosis of the subclinical hypothyroidism, with consideration of treatment during the first trimester, but not in the second or third trimester, based on newer evidence of the absolute risk for pregnancy complications and randomized trial data.

“The recommendations are now to no longer based on TPO antibody status, but instead according to the timing of the diagnosis of subclinical hypothyroidism,” Korevaar said.

Based on the collective data, “due to the low risk, we do not recommend for routine levothyroxine treatment in the second or third trimester groups with TSH levels under 10 mU/L now.”

“However, for subclinical hypothyroidism diagnosed in the first trimester, the recommendation would be that you can consider levothyroxine treatment,” he said.

While a clear indication for treatment in any trimester is the presence of overt hypothyroidism, or TSH levels over 10 mU/L, Korevaar underscored the importance of considering nuances of the recommendations that may warrant flexibility, for instance among patients with borderline TSH levels.
 

Spontaneous Normalization of Thyroid Levels in Pregnancy

Another new recommendation addresses the issue of spontaneous normalization of abnormal thyroid function during pregnancy, with several large studies showing a large proportion of subclinical hypothyroidism cases spontaneously revert to euthyroidism by the third trimester — despite no treatment having been provided.

Under the important proposed recommendation, retesting of subclinical hypothyroidism is suggested within 3 weeks.

“The data shows that a large proportion of patients spontaneously revert to euthyroidism,” Korevaar said.

“Upon identifying subclinical hypothyroidism in the first trimester, there will be essentially two options that clinicians can discuss with their patient — one would be to consider confirmatory tests in 3 weeks or to discuss the starting the lower dose levothyroxine in the first trimester,” he said.

In terms of overt hypothyroidism, likewise, if patients have a TSH levels below 6 mU/L in pregnancy, “you can either consider doing confirmatory testing within 3 weeks, or discussing with the patient starting levothyroxine treatment,” Korevaar added.
 

Overt Hyperthyroidism

For overt hyperthyroidism, no significant changes from current guidelines are being proposed, with the key exception of a heightened emphasis on the need for shared decision-making with patients, Korevaar said.

“We want to emphasize shared decision-making especially for women who have Graves’ disease prior to pregnancy, because the antithyroid treatment modalities, primarily methimazole (MMI) and propylthiouracil (PTU), have different advantages and disadvantages for an upcoming pregnancy,” he said.

“If you help a patient become involved in the decision-making process, that can also be very helpful in managing the disease and following-up on the pregnancy.”

Under the recommendations, PTU remains the preferred drug in overt hyperthyroidism, due to a more favorable profile in terms of potential birth defects vs MMI, with research showing a higher absolute risk of 3% vs 5%.

The guidelines further suggest the option of stopping the antithyroid medications upon a positive pregnancy test, with the exception of high-risk patients.

Korevaar noted that, if the treatment is stopped early in pregnancy, relapse is not likely to occur until after approximately 3 months, or 12 weeks, at which time, the high-risk teratogenic period, which is between week 5 and week 15, will have passed.

Current guidelines regarding whether to stop treatment in higher-risk hyperthyroid patients are recommended to remain unchanged.
 

Thyroid Nodules and Cancer

Recommendations regarding thyroid nodules and cancer during pregnancy are also expected to remain largely similar to those in the 2017 guidelines, with the exception of an emphasis on simply considering how the patient would normally be managed outside of pregnancy. 

For instance, regarding the question of whether treatment can be withheld for 9 months during pregnancy. “A lot of times, the answer is yes,” Korevaar said.

Other topics that will be largely unchanged include issues of universal screening, definitions of normal and abnormal TSH and free T4 reference ranges and isolated hypothyroxinemia.
 

Steps Forward in Improving Updates, Readability

In addition to recommendation updates, the new guidelines are being revised to better reflect more recent evidence-based developments and user-friendliness.

“We have now made the step to a more systematic and replicable methodology to ensure for easier updates with a shorter interval,” Korevaar told this news organization.

“Furthermore, since 2006, the ATA guideline documents have followed a question-and-answer format, lacked recommendation tables and had none or only a few graphic illustrations,” he added. 

“We are now further developing the typical outline of the guidelines to improve the readability and dissemination of the guideline document.”

Korevaar’s disclosures include lectureship fees from IBSA, Merck, and Berlin Chemie.

A version of this article first appeared on Medscape.com.

CHICAGO — A preview of much-anticipated updates to guidelines on managing thyroid disease in pregnancy shows key changes to recommendations in the evolving field, ranging from consideration of the chance of spontaneous normalization of thyroid levels during pregnancy to a heightened emphasis on shared decision-making and the nuances can factor into personalized treatment.

The guidelines, expected to be published in early 2025, have not been updated since 2017, and with substantial advances and evidence from countless studies since then, the new guidelines were developed with a goal to start afresh, said ATA Thyroid and Pregnancy Guidelines Task Force cochair Tim IM Korevaar, MD, PhD, in presenting the final draft guidelines at the American Thyroid Association (ATA) 2024 Meeting.

“Obviously, we’re not going to ignore the 2017 guidelines, which have been a very good resource for us so far, but we really wanted to start from scratch and follow a ‘blank canvas’ approach in optimizing the evidence,” said Korevaar, an endocrinologist and obstetric internist with the Division of Pharmacology and Vascular Medicine & Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

The guidelines, developed through a collaborative effort involving a wide variety of related medical societies, involved 14 systematic literature reviews. While the pregnancy issues covered by the guidelines is extensive, key highlights include:
 

Management in Preconception

Beginning with preconception, a key change in the guidelines will be that patients with euthyroid thyroid peroxidase (TPO) antibodies, which can be indicative of thyroid dysfunction, routine treatment with levothyroxine is not recommended, based on new evidence from randomized trials of high-risk patients showing no clear benefit from the treatment. 

“In these trials, and across analyses, there was absolutely no beneficial effect of levothyroxine in these patients [with euthyroid TPO antibody positivity],” he said.

With evidence showing, however, that TPO antibody positivity can lead to subclinical or overt hypothyroidism within 1 or 2 years, the guidelines will recommend that TPO antibody–positive patients do have thyroid stimulating hormone (TSH) levels tested every 3-6 months until pregnancy, and existing recommendations to test during pregnancy among those patients remain in place, Korevaar reported.

In terms of preconception subclinical hypothyroidism, the guidelines will emphasize the existing recommendation “to always strive to reassess” thyroid levels, and if subclinical hypothyroidism does persist, to treat with low-dose levothyroxine.
 

During Pregnancy

During pregnancy, the new proposed recommendations will reflect the important change that three key risk factors, including age over 30 years, having at least two prior pregnancies, and morbid obesity (body mass index [BMI] at least 40 kg/m²), previously considered a risk for thyroid dysfunction in pregnancy, should not, on their own, suggest the need for thyroid testing, based on low evidence of an increased risk in pregnancy.

Research on the issue includes a recent study from Korevaar’s team showing these factors to in fact have low predictability of thyroid dysfunction.

“We deemed that these risk differences weren’t really clinically meaningful (in predicting risk), and so we have removed to maternal age, BMI, and parity as risk factors for thyroid testing indications in pregnancy,” Korevaar said.

Factors considered a risk, resulting in recommended testing at presentation include a history of subclinical or clinical hypo- or hyperthyroidism, postpartum thyroiditis, known thyroid antibody positivity, symptoms of thyroid dysfunction or goiter, and other factors. 
 

Treatment for Subclinical Hypothyroidism in Pregnancy

Whereas current guidelines recommend TPO antibody status in determining when to consider treatment for subclinical hypothyroidism, the new proposed guideline will instead recommend treatment based on the timing of the diagnosis of the subclinical hypothyroidism, with consideration of treatment during the first trimester, but not in the second or third trimester, based on newer evidence of the absolute risk for pregnancy complications and randomized trial data.

“The recommendations are now to no longer based on TPO antibody status, but instead according to the timing of the diagnosis of subclinical hypothyroidism,” Korevaar said.

Based on the collective data, “due to the low risk, we do not recommend for routine levothyroxine treatment in the second or third trimester groups with TSH levels under 10 mU/L now.”

“However, for subclinical hypothyroidism diagnosed in the first trimester, the recommendation would be that you can consider levothyroxine treatment,” he said.

While a clear indication for treatment in any trimester is the presence of overt hypothyroidism, or TSH levels over 10 mU/L, Korevaar underscored the importance of considering nuances of the recommendations that may warrant flexibility, for instance among patients with borderline TSH levels.
 

Spontaneous Normalization of Thyroid Levels in Pregnancy

Another new recommendation addresses the issue of spontaneous normalization of abnormal thyroid function during pregnancy, with several large studies showing a large proportion of subclinical hypothyroidism cases spontaneously revert to euthyroidism by the third trimester — despite no treatment having been provided.

Under the important proposed recommendation, retesting of subclinical hypothyroidism is suggested within 3 weeks.

“The data shows that a large proportion of patients spontaneously revert to euthyroidism,” Korevaar said.

“Upon identifying subclinical hypothyroidism in the first trimester, there will be essentially two options that clinicians can discuss with their patient — one would be to consider confirmatory tests in 3 weeks or to discuss the starting the lower dose levothyroxine in the first trimester,” he said.

In terms of overt hypothyroidism, likewise, if patients have a TSH levels below 6 mU/L in pregnancy, “you can either consider doing confirmatory testing within 3 weeks, or discussing with the patient starting levothyroxine treatment,” Korevaar added.
 

Overt Hyperthyroidism

For overt hyperthyroidism, no significant changes from current guidelines are being proposed, with the key exception of a heightened emphasis on the need for shared decision-making with patients, Korevaar said.

“We want to emphasize shared decision-making especially for women who have Graves’ disease prior to pregnancy, because the antithyroid treatment modalities, primarily methimazole (MMI) and propylthiouracil (PTU), have different advantages and disadvantages for an upcoming pregnancy,” he said.

“If you help a patient become involved in the decision-making process, that can also be very helpful in managing the disease and following-up on the pregnancy.”

Under the recommendations, PTU remains the preferred drug in overt hyperthyroidism, due to a more favorable profile in terms of potential birth defects vs MMI, with research showing a higher absolute risk of 3% vs 5%.

The guidelines further suggest the option of stopping the antithyroid medications upon a positive pregnancy test, with the exception of high-risk patients.

Korevaar noted that, if the treatment is stopped early in pregnancy, relapse is not likely to occur until after approximately 3 months, or 12 weeks, at which time, the high-risk teratogenic period, which is between week 5 and week 15, will have passed.

Current guidelines regarding whether to stop treatment in higher-risk hyperthyroid patients are recommended to remain unchanged.
 

Thyroid Nodules and Cancer

Recommendations regarding thyroid nodules and cancer during pregnancy are also expected to remain largely similar to those in the 2017 guidelines, with the exception of an emphasis on simply considering how the patient would normally be managed outside of pregnancy. 

For instance, regarding the question of whether treatment can be withheld for 9 months during pregnancy. “A lot of times, the answer is yes,” Korevaar said.

Other topics that will be largely unchanged include issues of universal screening, definitions of normal and abnormal TSH and free T4 reference ranges and isolated hypothyroxinemia.
 

Steps Forward in Improving Updates, Readability

In addition to recommendation updates, the new guidelines are being revised to better reflect more recent evidence-based developments and user-friendliness.

“We have now made the step to a more systematic and replicable methodology to ensure for easier updates with a shorter interval,” Korevaar told this news organization.

“Furthermore, since 2006, the ATA guideline documents have followed a question-and-answer format, lacked recommendation tables and had none or only a few graphic illustrations,” he added. 

“We are now further developing the typical outline of the guidelines to improve the readability and dissemination of the guideline document.”

Korevaar’s disclosures include lectureship fees from IBSA, Merck, and Berlin Chemie.

A version of this article first appeared on Medscape.com.

CHICAGO — A preview of much-anticipated updates to guidelines on managing thyroid disease in pregnancy shows key changes to recommendations in the evolving field, ranging from consideration of the chance of spontaneous normalization of thyroid levels during pregnancy to a heightened emphasis on shared decision-making and the nuances can factor into personalized treatment.

The guidelines, expected to be published in early 2025, have not been updated since 2017, and with substantial advances and evidence from countless studies since then, the new guidelines were developed with a goal to start afresh, said ATA Thyroid and Pregnancy Guidelines Task Force cochair Tim IM Korevaar, MD, PhD, in presenting the final draft guidelines at the American Thyroid Association (ATA) 2024 Meeting.

“Obviously, we’re not going to ignore the 2017 guidelines, which have been a very good resource for us so far, but we really wanted to start from scratch and follow a ‘blank canvas’ approach in optimizing the evidence,” said Korevaar, an endocrinologist and obstetric internist with the Division of Pharmacology and Vascular Medicine & Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

The guidelines, developed through a collaborative effort involving a wide variety of related medical societies, involved 14 systematic literature reviews. While the pregnancy issues covered by the guidelines is extensive, key highlights include:
 

Management in Preconception

Beginning with preconception, a key change in the guidelines will be that patients with euthyroid thyroid peroxidase (TPO) antibodies, which can be indicative of thyroid dysfunction, routine treatment with levothyroxine is not recommended, based on new evidence from randomized trials of high-risk patients showing no clear benefit from the treatment. 

“In these trials, and across analyses, there was absolutely no beneficial effect of levothyroxine in these patients [with euthyroid TPO antibody positivity],” he said.

With evidence showing, however, that TPO antibody positivity can lead to subclinical or overt hypothyroidism within 1 or 2 years, the guidelines will recommend that TPO antibody–positive patients do have thyroid stimulating hormone (TSH) levels tested every 3-6 months until pregnancy, and existing recommendations to test during pregnancy among those patients remain in place, Korevaar reported.

In terms of preconception subclinical hypothyroidism, the guidelines will emphasize the existing recommendation “to always strive to reassess” thyroid levels, and if subclinical hypothyroidism does persist, to treat with low-dose levothyroxine.
 

During Pregnancy

During pregnancy, the new proposed recommendations will reflect the important change that three key risk factors, including age over 30 years, having at least two prior pregnancies, and morbid obesity (body mass index [BMI] at least 40 kg/m²), previously considered a risk for thyroid dysfunction in pregnancy, should not, on their own, suggest the need for thyroid testing, based on low evidence of an increased risk in pregnancy.

Research on the issue includes a recent study from Korevaar’s team showing these factors to in fact have low predictability of thyroid dysfunction.

“We deemed that these risk differences weren’t really clinically meaningful (in predicting risk), and so we have removed to maternal age, BMI, and parity as risk factors for thyroid testing indications in pregnancy,” Korevaar said.

Factors considered a risk, resulting in recommended testing at presentation include a history of subclinical or clinical hypo- or hyperthyroidism, postpartum thyroiditis, known thyroid antibody positivity, symptoms of thyroid dysfunction or goiter, and other factors. 
 

Treatment for Subclinical Hypothyroidism in Pregnancy

Whereas current guidelines recommend TPO antibody status in determining when to consider treatment for subclinical hypothyroidism, the new proposed guideline will instead recommend treatment based on the timing of the diagnosis of the subclinical hypothyroidism, with consideration of treatment during the first trimester, but not in the second or third trimester, based on newer evidence of the absolute risk for pregnancy complications and randomized trial data.

“The recommendations are now to no longer based on TPO antibody status, but instead according to the timing of the diagnosis of subclinical hypothyroidism,” Korevaar said.

Based on the collective data, “due to the low risk, we do not recommend for routine levothyroxine treatment in the second or third trimester groups with TSH levels under 10 mU/L now.”

“However, for subclinical hypothyroidism diagnosed in the first trimester, the recommendation would be that you can consider levothyroxine treatment,” he said.

While a clear indication for treatment in any trimester is the presence of overt hypothyroidism, or TSH levels over 10 mU/L, Korevaar underscored the importance of considering nuances of the recommendations that may warrant flexibility, for instance among patients with borderline TSH levels.
 

Spontaneous Normalization of Thyroid Levels in Pregnancy

Another new recommendation addresses the issue of spontaneous normalization of abnormal thyroid function during pregnancy, with several large studies showing a large proportion of subclinical hypothyroidism cases spontaneously revert to euthyroidism by the third trimester — despite no treatment having been provided.

Under the important proposed recommendation, retesting of subclinical hypothyroidism is suggested within 3 weeks.

“The data shows that a large proportion of patients spontaneously revert to euthyroidism,” Korevaar said.

“Upon identifying subclinical hypothyroidism in the first trimester, there will be essentially two options that clinicians can discuss with their patient — one would be to consider confirmatory tests in 3 weeks or to discuss the starting the lower dose levothyroxine in the first trimester,” he said.

In terms of overt hypothyroidism, likewise, if patients have a TSH levels below 6 mU/L in pregnancy, “you can either consider doing confirmatory testing within 3 weeks, or discussing with the patient starting levothyroxine treatment,” Korevaar added.
 

Overt Hyperthyroidism

For overt hyperthyroidism, no significant changes from current guidelines are being proposed, with the key exception of a heightened emphasis on the need for shared decision-making with patients, Korevaar said.

“We want to emphasize shared decision-making especially for women who have Graves’ disease prior to pregnancy, because the antithyroid treatment modalities, primarily methimazole (MMI) and propylthiouracil (PTU), have different advantages and disadvantages for an upcoming pregnancy,” he said.

“If you help a patient become involved in the decision-making process, that can also be very helpful in managing the disease and following-up on the pregnancy.”

Under the recommendations, PTU remains the preferred drug in overt hyperthyroidism, due to a more favorable profile in terms of potential birth defects vs MMI, with research showing a higher absolute risk of 3% vs 5%.

The guidelines further suggest the option of stopping the antithyroid medications upon a positive pregnancy test, with the exception of high-risk patients.

Korevaar noted that, if the treatment is stopped early in pregnancy, relapse is not likely to occur until after approximately 3 months, or 12 weeks, at which time, the high-risk teratogenic period, which is between week 5 and week 15, will have passed.

Current guidelines regarding whether to stop treatment in higher-risk hyperthyroid patients are recommended to remain unchanged.
 

Thyroid Nodules and Cancer

Recommendations regarding thyroid nodules and cancer during pregnancy are also expected to remain largely similar to those in the 2017 guidelines, with the exception of an emphasis on simply considering how the patient would normally be managed outside of pregnancy. 

For instance, regarding the question of whether treatment can be withheld for 9 months during pregnancy. “A lot of times, the answer is yes,” Korevaar said.

Other topics that will be largely unchanged include issues of universal screening, definitions of normal and abnormal TSH and free T4 reference ranges and isolated hypothyroxinemia.
 

Steps Forward in Improving Updates, Readability

In addition to recommendation updates, the new guidelines are being revised to better reflect more recent evidence-based developments and user-friendliness.

“We have now made the step to a more systematic and replicable methodology to ensure for easier updates with a shorter interval,” Korevaar told this news organization.

“Furthermore, since 2006, the ATA guideline documents have followed a question-and-answer format, lacked recommendation tables and had none or only a few graphic illustrations,” he added. 

“We are now further developing the typical outline of the guidelines to improve the readability and dissemination of the guideline document.”

Korevaar’s disclosures include lectureship fees from IBSA, Merck, and Berlin Chemie.

A version of this article first appeared on Medscape.com.

More than one third of patients with cancer visited an emergency department (ED) in the 90 days before their diagnosis, according to a study of medical records from Ontario, Canada.

Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.

Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.

“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”

The findings were published online on November 4 in CMAJ).
 

Neurologic Cancers Prominent

In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.

Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.

Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.

Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).

The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.

“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.

The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.

The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
 

‘Unpacking the Data’

The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.

“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.

“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”

All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.

“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.

This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

More than one third of patients with cancer visited an emergency department (ED) in the 90 days before their diagnosis, according to a study of medical records from Ontario, Canada.

Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.

Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.

“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”

The findings were published online on November 4 in CMAJ).
 

Neurologic Cancers Prominent

In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.

Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.

Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.

Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).

The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.

“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.

The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.

The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
 

‘Unpacking the Data’

The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.

“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.

“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”

All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.

“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.

This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

More than one third of patients with cancer visited an emergency department (ED) in the 90 days before their diagnosis, according to a study of medical records from Ontario, Canada.

Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.

Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.

“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”

The findings were published online on November 4 in CMAJ).
 

Neurologic Cancers Prominent

In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.

Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.

Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.

Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).

The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.

“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.

The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.

The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
 

‘Unpacking the Data’

The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.

“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.

“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”

All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.

“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.

This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

First, there were “Ozempic babies.” Now, there is also Ozempic-before-baby.

Unplanned pregnancies are still regularly being reported among people using glucagon-like peptide 1 receptor agonist (GLP-1 RA) drugs, and now fertility specialists are increasingly incorporating the medicines into preconception care plans.

The specialists say their colleagues in other areas of medicine may have an opportunity, too, to talk about weight loss using these new drugs in terms of reproductive health. Motivation and compliance can transform when the goal isn’t simply weight loss but having children.

“We have this really special moment to help patients be healthier, in order to be healthier for their kids,” said Christina Boots, MD, MSci, an associate professor of reproductive endocrinology and infertility at Northwestern University’s Feinberg School of Medicine, Chicago. “And I think that’s also a very motivating moment. It may be hard to get up and go for a run to make my jeans fit better, but when I think about it in terms of, ‘this might someday help my future daughter,’ that is a whole different level of motivation.”

Discussing obesity treatment can be a delicate conversation, but one that would be beneficial to have with any patient of reproductive age. Here’s why, what to know about the current lengthy list of unknowns and risks, and some options for approaching the topic with patients.
 

What Fertility Docs Are Doing

While overweight and obesity are consistently linked to fertility and pregnancy outcomes, Boots predicts the biggest impact of GLP-1 weight loss for fertility among women will be a specific subset: Those who are not cycling regularly, such as those with polycystic ovary syndrome (PCOS).

“The women who are cycling regularly who have very unexplained infertility and no other comorbidities like high blood pressure or something else going on, I don’t think it’s going to help their fertility very much at all,” she said “It might, but I think there’s probably something else going on in her tubes or with her eggs or his sperm, but it has nothing to do with her metabolic health.

Women who aren’t cycling regularly will benefit, but those with truly unexplained fertility probably won’t, she said.

In their recent narrative review on treating obesity and fertility with GLP-1 RAs that appeared in Fertility and Sterility, Boots and co-author Alyse S. Goldberg, MD, an endocrinologist with the University of Toronto, Ontario, Canada, advocate for the use of GLP-1s as a go-to treatment for obesity as part of preconception care by reproductive endocrinologists, calling the drugs “the most effective, least invasive means of weight loss.”

The paper is timely and necessary because use of GLP-1s is only going to increase, Patricia Jimenez, MD, an associate professor of obstetrics and gynecology at Washington University School of Medicine in St. Louis, Missouri, said in an email to this news organization.

“GLP-1 RAs are becoming a larger part of my practice. More patients are either using them already or interested in using them,” said Jimenez, who is board certified in reproductive endocrinology, obstetrics and gynecology, and obesity medicine. “I specifically see patients to discuss this and do prescribe antiobesity medications, not only GLP-1 RAs. Often this is with people with PCOS who are not planning to conceive soon or patients willing to delay fertility treatment [by] 3-6 months.”

Treating obesity is also important for women who are seeking in vitro fertilization, Boots said, because many IVF clinics have a body mass index cutoff of 40 kg/m².

Like Jimenez’s approach, Boots and Goldberg call for comprehensive obesity care beyond the use of medication, including nutritional counseling and mental health support. Those supports are important during the transition off of GLP-1 medications, which poses a risk for rapid weight regain. That’s even with the potential support of taking metformin, which Boots often prescribes as a bridge.

Semaglutide should be stopped at least 2 months prior to conception, and tirzepatide should be stopped 1 month prior to conception, according to the manufacturers. (Boots and Goldberg listed the Canadian label recommendation for stopping tirzepatide, noting there is no suggested timeline for stopping prior to conception on the US label.)

Numerous studies have shown rapid weight regain is common when stopping GLP-1s, which presents a unique set of risks for pregnant women including early pregnancy loss, gestational diabetes, preeclampsia, and nonelective cesarean delivery.
 

Weighing Risks, Benefits, and Unknowns

Early looks at small human data sets, mostly involving semaglutide and earlier short-acting GLP-1s, and their impact on the risk for birth defects are “reassuring,” Boots said.

“But birth defects are just one small aspect. There’s also metabolic health and things like that long-term. Understanding what it does to the growing baby and the proximity of that medication to that growing baby is really important to see, and can’t be answered with animal studies, not perfectly anyway,” Boots said.

There are no published reports, from clinical trials nor case collections, examining the use of tirzepatide among pregnant people.

“One of the most important questions we need to answer is the preconception safety of these medications, and that includes safety for men,” Joshua Halpern, MD, MS, an adjunct assistant professor of urology at Northwestern University’s Feinberg School of Medicine, and chief scientific officer for Posterity Health, said in an email to this news organization.

“For example, a recent study found that men who were taking metformin, another popular medication for diabetes, were more likely to have children with birth defects, compared with those who were not taking the medication,” Halpern said. “Further studies are needed to determine whether a similar effect might hold true for the GLP-1 agonists.”

Small early studies on sperm are encouraging, Halpern said, suggesting that GLP-1 use may be beneficial, but a better understanding of direct effects is needed.

Among women, there may be cases where continuing use of a GLP-1 during pregnancy may offer benefits that outweigh risks, Boots suggested. Manufacturers have also created pregnancy exposure registries to measure the safety of their therapies during pregnancy.

“I have a group of patients whose sugars are so well controlled on these medications, but as soon as they come off, they get weight regain and their glucose is just so poorly controlled,” she said. “There may be a group of women where the benefits of glucose control outweigh the risks of being on the medication the whole pregnancy.”

The list of important unknowns also includes a need to examine how rapid weight loss may impact ovulation rates and spontaneous conception, as well as miscarriage rates, birth weight, and metabolic health of the child.

More detailed rebound weight gain data is coming next year, with additional analysis expected as well on birth weight and pregnancy outcomes, said Jacqueline Maya, MD, first author of the research abstract presented at this year’s American Diabetes Association conference that examined gestational weight gain among people with preexisting type 2 diabetes who were exposed to GLP-1s during pregnancy. The study included 47 exposed pregnancies (based on prescription records and electronic chart information) and compared gestational weight gain to 141 unexposed matched pregnancies. Among the exposed group, 62% exceeded recommended weight gain, compared with 41% in the unexposed group. On average, gestational weight gain in exposed pregnancies exceeded that among matched unexposed pregnancies by about 6 pounds.

The team is now working with an additional data set to examine exposed pregnancies among people with obesity, said Maya, an instructor of pediatrics at Mass General Hospital and Harvard School of Medicine. She is particularly interested in examining weight trajectories during pregnancy to see how they may affect fetal outcomes. Her team’s current project also will likely include analysis to examine other variables like postpartum weight gain and adiposity characteristics of the baby.

Maya said the team hopes to have more to report at the American Diabetes Association conference in June next year.
 

Offer the Conversation

Using a GLP-1 for weight loss takes time, usually around 1 year to reach a plateau. Boots encouraged nonfertility providers to ask patients of reproductive age about their family plans as an opening.

“I hope for all primary care doctors and gynecologists, that with any patient of reproductive age, you should be bringing this up, asking, ‘Have you thought about having kids? Are you thinking about it soon?’ And if they say they are sometime in the near future, then you can say, ‘Is it OK if I bring up your weight?’ And you should ask permission.”

If the patient declines, it’s OK to bring it up again at a future visit.

“People with obesity have often experienced negative weight bias that impacts their care,” Jimenez said. “Treat obesity as a disease, not a personal failing. Ask permission to discuss weight with the patient beforehand. If they say no, respect that answer. This goes a long way in developing a positive relationship, so they return for care and may be willing to discuss later.” 

When patients are open to the conversation, Boots suggests not focusing on the potential for poor outcomes, and instead perhaps saying, “If you’re thinking about having a baby in 5 years, optimizing your health now will not only make your pregnancy healthier, but your child healthier long-term.”

Discussing contraception plans remains important. People starting semaglutide or tirzepatide should use contraception other than oral birth control for 4 weeks while starting the medicine and for 4 weeks after each dose increase.

Boots said that the contraception conversation is particularly important because many people have come to deeply believe that they are infertile and, thus, may perhaps think contraception advice doesn’t apply to them. Maya hypothesized that behavioral changes following weight loss may also be a pathway toward pregnancy.

“Pregnancy while on GLP-1 RAs does happen. I always have a discussion about this possibility and contraception. This can sometimes be challenging for people with infertility to consider,” Jimenez said. “Explaining the risks, benefits, and unknowns can help. As the [Fertility and Sterility] paper describes, the limited data available has not shown increased fetal or maternal complications. We need more high quality data to better understand the impact of exposure or use around the time of conception and during pregnancy.”

It’s also important to introduce the idea to patients that they may someday need to come off the medications, such as when they are ready to have children, and how important lifestyle and behavioral changes will be at that time, Maya said.

“We do know what the alternative is, and we do know what the risks of obesity are,” she said. “So, it’s a tug and pull. We’re not starting off with healthy. We’re starting off with a disease that is physically and emotionally very difficult for the patient, especially when it starts in childhood.”
 

A version of this article appeared on Medscape.com.

First, there were “Ozempic babies.” Now, there is also Ozempic-before-baby.

Unplanned pregnancies are still regularly being reported among people using glucagon-like peptide 1 receptor agonist (GLP-1 RA) drugs, and now fertility specialists are increasingly incorporating the medicines into preconception care plans.

The specialists say their colleagues in other areas of medicine may have an opportunity, too, to talk about weight loss using these new drugs in terms of reproductive health. Motivation and compliance can transform when the goal isn’t simply weight loss but having children.

“We have this really special moment to help patients be healthier, in order to be healthier for their kids,” said Christina Boots, MD, MSci, an associate professor of reproductive endocrinology and infertility at Northwestern University’s Feinberg School of Medicine, Chicago. “And I think that’s also a very motivating moment. It may be hard to get up and go for a run to make my jeans fit better, but when I think about it in terms of, ‘this might someday help my future daughter,’ that is a whole different level of motivation.”

Discussing obesity treatment can be a delicate conversation, but one that would be beneficial to have with any patient of reproductive age. Here’s why, what to know about the current lengthy list of unknowns and risks, and some options for approaching the topic with patients.
 

What Fertility Docs Are Doing

While overweight and obesity are consistently linked to fertility and pregnancy outcomes, Boots predicts the biggest impact of GLP-1 weight loss for fertility among women will be a specific subset: Those who are not cycling regularly, such as those with polycystic ovary syndrome (PCOS).

“The women who are cycling regularly who have very unexplained infertility and no other comorbidities like high blood pressure or something else going on, I don’t think it’s going to help their fertility very much at all,” she said “It might, but I think there’s probably something else going on in her tubes or with her eggs or his sperm, but it has nothing to do with her metabolic health.

Women who aren’t cycling regularly will benefit, but those with truly unexplained fertility probably won’t, she said.

In their recent narrative review on treating obesity and fertility with GLP-1 RAs that appeared in Fertility and Sterility, Boots and co-author Alyse S. Goldberg, MD, an endocrinologist with the University of Toronto, Ontario, Canada, advocate for the use of GLP-1s as a go-to treatment for obesity as part of preconception care by reproductive endocrinologists, calling the drugs “the most effective, least invasive means of weight loss.”

The paper is timely and necessary because use of GLP-1s is only going to increase, Patricia Jimenez, MD, an associate professor of obstetrics and gynecology at Washington University School of Medicine in St. Louis, Missouri, said in an email to this news organization.

“GLP-1 RAs are becoming a larger part of my practice. More patients are either using them already or interested in using them,” said Jimenez, who is board certified in reproductive endocrinology, obstetrics and gynecology, and obesity medicine. “I specifically see patients to discuss this and do prescribe antiobesity medications, not only GLP-1 RAs. Often this is with people with PCOS who are not planning to conceive soon or patients willing to delay fertility treatment [by] 3-6 months.”

Treating obesity is also important for women who are seeking in vitro fertilization, Boots said, because many IVF clinics have a body mass index cutoff of 40 kg/m².

Like Jimenez’s approach, Boots and Goldberg call for comprehensive obesity care beyond the use of medication, including nutritional counseling and mental health support. Those supports are important during the transition off of GLP-1 medications, which poses a risk for rapid weight regain. That’s even with the potential support of taking metformin, which Boots often prescribes as a bridge.

Semaglutide should be stopped at least 2 months prior to conception, and tirzepatide should be stopped 1 month prior to conception, according to the manufacturers. (Boots and Goldberg listed the Canadian label recommendation for stopping tirzepatide, noting there is no suggested timeline for stopping prior to conception on the US label.)

Numerous studies have shown rapid weight regain is common when stopping GLP-1s, which presents a unique set of risks for pregnant women including early pregnancy loss, gestational diabetes, preeclampsia, and nonelective cesarean delivery.
 

Weighing Risks, Benefits, and Unknowns

Early looks at small human data sets, mostly involving semaglutide and earlier short-acting GLP-1s, and their impact on the risk for birth defects are “reassuring,” Boots said.

“But birth defects are just one small aspect. There’s also metabolic health and things like that long-term. Understanding what it does to the growing baby and the proximity of that medication to that growing baby is really important to see, and can’t be answered with animal studies, not perfectly anyway,” Boots said.

There are no published reports, from clinical trials nor case collections, examining the use of tirzepatide among pregnant people.

“One of the most important questions we need to answer is the preconception safety of these medications, and that includes safety for men,” Joshua Halpern, MD, MS, an adjunct assistant professor of urology at Northwestern University’s Feinberg School of Medicine, and chief scientific officer for Posterity Health, said in an email to this news organization.

“For example, a recent study found that men who were taking metformin, another popular medication for diabetes, were more likely to have children with birth defects, compared with those who were not taking the medication,” Halpern said. “Further studies are needed to determine whether a similar effect might hold true for the GLP-1 agonists.”

Small early studies on sperm are encouraging, Halpern said, suggesting that GLP-1 use may be beneficial, but a better understanding of direct effects is needed.

Among women, there may be cases where continuing use of a GLP-1 during pregnancy may offer benefits that outweigh risks, Boots suggested. Manufacturers have also created pregnancy exposure registries to measure the safety of their therapies during pregnancy.

“I have a group of patients whose sugars are so well controlled on these medications, but as soon as they come off, they get weight regain and their glucose is just so poorly controlled,” she said. “There may be a group of women where the benefits of glucose control outweigh the risks of being on the medication the whole pregnancy.”

The list of important unknowns also includes a need to examine how rapid weight loss may impact ovulation rates and spontaneous conception, as well as miscarriage rates, birth weight, and metabolic health of the child.

More detailed rebound weight gain data is coming next year, with additional analysis expected as well on birth weight and pregnancy outcomes, said Jacqueline Maya, MD, first author of the research abstract presented at this year’s American Diabetes Association conference that examined gestational weight gain among people with preexisting type 2 diabetes who were exposed to GLP-1s during pregnancy. The study included 47 exposed pregnancies (based on prescription records and electronic chart information) and compared gestational weight gain to 141 unexposed matched pregnancies. Among the exposed group, 62% exceeded recommended weight gain, compared with 41% in the unexposed group. On average, gestational weight gain in exposed pregnancies exceeded that among matched unexposed pregnancies by about 6 pounds.

The team is now working with an additional data set to examine exposed pregnancies among people with obesity, said Maya, an instructor of pediatrics at Mass General Hospital and Harvard School of Medicine. She is particularly interested in examining weight trajectories during pregnancy to see how they may affect fetal outcomes. Her team’s current project also will likely include analysis to examine other variables like postpartum weight gain and adiposity characteristics of the baby.

Maya said the team hopes to have more to report at the American Diabetes Association conference in June next year.
 

Offer the Conversation

Using a GLP-1 for weight loss takes time, usually around 1 year to reach a plateau. Boots encouraged nonfertility providers to ask patients of reproductive age about their family plans as an opening.

“I hope for all primary care doctors and gynecologists, that with any patient of reproductive age, you should be bringing this up, asking, ‘Have you thought about having kids? Are you thinking about it soon?’ And if they say they are sometime in the near future, then you can say, ‘Is it OK if I bring up your weight?’ And you should ask permission.”

If the patient declines, it’s OK to bring it up again at a future visit.

“People with obesity have often experienced negative weight bias that impacts their care,” Jimenez said. “Treat obesity as a disease, not a personal failing. Ask permission to discuss weight with the patient beforehand. If they say no, respect that answer. This goes a long way in developing a positive relationship, so they return for care and may be willing to discuss later.” 

When patients are open to the conversation, Boots suggests not focusing on the potential for poor outcomes, and instead perhaps saying, “If you’re thinking about having a baby in 5 years, optimizing your health now will not only make your pregnancy healthier, but your child healthier long-term.”

Discussing contraception plans remains important. People starting semaglutide or tirzepatide should use contraception other than oral birth control for 4 weeks while starting the medicine and for 4 weeks after each dose increase.

Boots said that the contraception conversation is particularly important because many people have come to deeply believe that they are infertile and, thus, may perhaps think contraception advice doesn’t apply to them. Maya hypothesized that behavioral changes following weight loss may also be a pathway toward pregnancy.

“Pregnancy while on GLP-1 RAs does happen. I always have a discussion about this possibility and contraception. This can sometimes be challenging for people with infertility to consider,” Jimenez said. “Explaining the risks, benefits, and unknowns can help. As the [Fertility and Sterility] paper describes, the limited data available has not shown increased fetal or maternal complications. We need more high quality data to better understand the impact of exposure or use around the time of conception and during pregnancy.”

It’s also important to introduce the idea to patients that they may someday need to come off the medications, such as when they are ready to have children, and how important lifestyle and behavioral changes will be at that time, Maya said.

“We do know what the alternative is, and we do know what the risks of obesity are,” she said. “So, it’s a tug and pull. We’re not starting off with healthy. We’re starting off with a disease that is physically and emotionally very difficult for the patient, especially when it starts in childhood.”
 

A version of this article appeared on Medscape.com.

First, there were “Ozempic babies.” Now, there is also Ozempic-before-baby.

Unplanned pregnancies are still regularly being reported among people using glucagon-like peptide 1 receptor agonist (GLP-1 RA) drugs, and now fertility specialists are increasingly incorporating the medicines into preconception care plans.

The specialists say their colleagues in other areas of medicine may have an opportunity, too, to talk about weight loss using these new drugs in terms of reproductive health. Motivation and compliance can transform when the goal isn’t simply weight loss but having children.

“We have this really special moment to help patients be healthier, in order to be healthier for their kids,” said Christina Boots, MD, MSci, an associate professor of reproductive endocrinology and infertility at Northwestern University’s Feinberg School of Medicine, Chicago. “And I think that’s also a very motivating moment. It may be hard to get up and go for a run to make my jeans fit better, but when I think about it in terms of, ‘this might someday help my future daughter,’ that is a whole different level of motivation.”

Discussing obesity treatment can be a delicate conversation, but one that would be beneficial to have with any patient of reproductive age. Here’s why, what to know about the current lengthy list of unknowns and risks, and some options for approaching the topic with patients.
 

What Fertility Docs Are Doing

While overweight and obesity are consistently linked to fertility and pregnancy outcomes, Boots predicts the biggest impact of GLP-1 weight loss for fertility among women will be a specific subset: Those who are not cycling regularly, such as those with polycystic ovary syndrome (PCOS).

“The women who are cycling regularly who have very unexplained infertility and no other comorbidities like high blood pressure or something else going on, I don’t think it’s going to help their fertility very much at all,” she said “It might, but I think there’s probably something else going on in her tubes or with her eggs or his sperm, but it has nothing to do with her metabolic health.

Women who aren’t cycling regularly will benefit, but those with truly unexplained fertility probably won’t, she said.

In their recent narrative review on treating obesity and fertility with GLP-1 RAs that appeared in Fertility and Sterility, Boots and co-author Alyse S. Goldberg, MD, an endocrinologist with the University of Toronto, Ontario, Canada, advocate for the use of GLP-1s as a go-to treatment for obesity as part of preconception care by reproductive endocrinologists, calling the drugs “the most effective, least invasive means of weight loss.”

The paper is timely and necessary because use of GLP-1s is only going to increase, Patricia Jimenez, MD, an associate professor of obstetrics and gynecology at Washington University School of Medicine in St. Louis, Missouri, said in an email to this news organization.

“GLP-1 RAs are becoming a larger part of my practice. More patients are either using them already or interested in using them,” said Jimenez, who is board certified in reproductive endocrinology, obstetrics and gynecology, and obesity medicine. “I specifically see patients to discuss this and do prescribe antiobesity medications, not only GLP-1 RAs. Often this is with people with PCOS who are not planning to conceive soon or patients willing to delay fertility treatment [by] 3-6 months.”

Treating obesity is also important for women who are seeking in vitro fertilization, Boots said, because many IVF clinics have a body mass index cutoff of 40 kg/m².

Like Jimenez’s approach, Boots and Goldberg call for comprehensive obesity care beyond the use of medication, including nutritional counseling and mental health support. Those supports are important during the transition off of GLP-1 medications, which poses a risk for rapid weight regain. That’s even with the potential support of taking metformin, which Boots often prescribes as a bridge.

Semaglutide should be stopped at least 2 months prior to conception, and tirzepatide should be stopped 1 month prior to conception, according to the manufacturers. (Boots and Goldberg listed the Canadian label recommendation for stopping tirzepatide, noting there is no suggested timeline for stopping prior to conception on the US label.)

Numerous studies have shown rapid weight regain is common when stopping GLP-1s, which presents a unique set of risks for pregnant women including early pregnancy loss, gestational diabetes, preeclampsia, and nonelective cesarean delivery.
 

Weighing Risks, Benefits, and Unknowns

Early looks at small human data sets, mostly involving semaglutide and earlier short-acting GLP-1s, and their impact on the risk for birth defects are “reassuring,” Boots said.

“But birth defects are just one small aspect. There’s also metabolic health and things like that long-term. Understanding what it does to the growing baby and the proximity of that medication to that growing baby is really important to see, and can’t be answered with animal studies, not perfectly anyway,” Boots said.

There are no published reports, from clinical trials nor case collections, examining the use of tirzepatide among pregnant people.

“One of the most important questions we need to answer is the preconception safety of these medications, and that includes safety for men,” Joshua Halpern, MD, MS, an adjunct assistant professor of urology at Northwestern University’s Feinberg School of Medicine, and chief scientific officer for Posterity Health, said in an email to this news organization.

“For example, a recent study found that men who were taking metformin, another popular medication for diabetes, were more likely to have children with birth defects, compared with those who were not taking the medication,” Halpern said. “Further studies are needed to determine whether a similar effect might hold true for the GLP-1 agonists.”

Small early studies on sperm are encouraging, Halpern said, suggesting that GLP-1 use may be beneficial, but a better understanding of direct effects is needed.

Among women, there may be cases where continuing use of a GLP-1 during pregnancy may offer benefits that outweigh risks, Boots suggested. Manufacturers have also created pregnancy exposure registries to measure the safety of their therapies during pregnancy.

“I have a group of patients whose sugars are so well controlled on these medications, but as soon as they come off, they get weight regain and their glucose is just so poorly controlled,” she said. “There may be a group of women where the benefits of glucose control outweigh the risks of being on the medication the whole pregnancy.”

The list of important unknowns also includes a need to examine how rapid weight loss may impact ovulation rates and spontaneous conception, as well as miscarriage rates, birth weight, and metabolic health of the child.

More detailed rebound weight gain data is coming next year, with additional analysis expected as well on birth weight and pregnancy outcomes, said Jacqueline Maya, MD, first author of the research abstract presented at this year’s American Diabetes Association conference that examined gestational weight gain among people with preexisting type 2 diabetes who were exposed to GLP-1s during pregnancy. The study included 47 exposed pregnancies (based on prescription records and electronic chart information) and compared gestational weight gain to 141 unexposed matched pregnancies. Among the exposed group, 62% exceeded recommended weight gain, compared with 41% in the unexposed group. On average, gestational weight gain in exposed pregnancies exceeded that among matched unexposed pregnancies by about 6 pounds.

The team is now working with an additional data set to examine exposed pregnancies among people with obesity, said Maya, an instructor of pediatrics at Mass General Hospital and Harvard School of Medicine. She is particularly interested in examining weight trajectories during pregnancy to see how they may affect fetal outcomes. Her team’s current project also will likely include analysis to examine other variables like postpartum weight gain and adiposity characteristics of the baby.

Maya said the team hopes to have more to report at the American Diabetes Association conference in June next year.
 

Offer the Conversation

Using a GLP-1 for weight loss takes time, usually around 1 year to reach a plateau. Boots encouraged nonfertility providers to ask patients of reproductive age about their family plans as an opening.

“I hope for all primary care doctors and gynecologists, that with any patient of reproductive age, you should be bringing this up, asking, ‘Have you thought about having kids? Are you thinking about it soon?’ And if they say they are sometime in the near future, then you can say, ‘Is it OK if I bring up your weight?’ And you should ask permission.”

If the patient declines, it’s OK to bring it up again at a future visit.

“People with obesity have often experienced negative weight bias that impacts their care,” Jimenez said. “Treat obesity as a disease, not a personal failing. Ask permission to discuss weight with the patient beforehand. If they say no, respect that answer. This goes a long way in developing a positive relationship, so they return for care and may be willing to discuss later.” 

When patients are open to the conversation, Boots suggests not focusing on the potential for poor outcomes, and instead perhaps saying, “If you’re thinking about having a baby in 5 years, optimizing your health now will not only make your pregnancy healthier, but your child healthier long-term.”

Discussing contraception plans remains important. People starting semaglutide or tirzepatide should use contraception other than oral birth control for 4 weeks while starting the medicine and for 4 weeks after each dose increase.

Boots said that the contraception conversation is particularly important because many people have come to deeply believe that they are infertile and, thus, may perhaps think contraception advice doesn’t apply to them. Maya hypothesized that behavioral changes following weight loss may also be a pathway toward pregnancy.

“Pregnancy while on GLP-1 RAs does happen. I always have a discussion about this possibility and contraception. This can sometimes be challenging for people with infertility to consider,” Jimenez said. “Explaining the risks, benefits, and unknowns can help. As the [Fertility and Sterility] paper describes, the limited data available has not shown increased fetal or maternal complications. We need more high quality data to better understand the impact of exposure or use around the time of conception and during pregnancy.”

It’s also important to introduce the idea to patients that they may someday need to come off the medications, such as when they are ready to have children, and how important lifestyle and behavioral changes will be at that time, Maya said.

“We do know what the alternative is, and we do know what the risks of obesity are,” she said. “So, it’s a tug and pull. We’re not starting off with healthy. We’re starting off with a disease that is physically and emotionally very difficult for the patient, especially when it starts in childhood.”
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Several types of anti-obesity medications (AOMs), including glucagon-like peptide 1s (GLP-1s), are associated with decreased alcohol use, new research suggests.

The findings, from surveys of more than 14,000 participants in WeightWatchers’ telehealth weight management program, were presented on November 6 at the Obesity Society’s Obesity Week 2024 meeting by the company’s Chief Nutrition Officer, Michelle I. Cardel, PhD, RD, based in Gainesville, Florida.

Similar reductions in alcohol consumption were seen in people taking different classes of AOMs, suggesting “an additional mechanism by which AOMs reduce energy intake, and also signal a potential role for these medications to reduce alcohol use,” Cardel said, adding “Clinicians treating individuals for obesity may consider anti-obesity medications particularly among those who report higher alcohol intake.”

Asked to comment, session moderator and obesity researcher Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said, “I think there are some overlapping pathways there, possibly a reward system or something like that in the brain. I don’t think we know exactly what the end result will be as a potential use of the medications. But there’s a signal that needs to be investigated more.”

Cardel noted that there was one previous large cohort study finding that semaglutide was associated with a lower risk for alcohol use disorder, and another study that analyzed social media threads of people saying they’d quit drinking after starting a GLP-1 drug. But this new study is the first to examine the relationship with different classes of AOMs and to quantify the amount of alcohol consumed.
 

About Half Reported Reduced Alcohol Consumption, Regardless the AOM Class

The study included 14,053 WeightWatchers’ telehealth program participants who initiated an AOM between January 2022 and August 2023 and refilled the same AOM between October and November 2023. Those who had previously used AOMs before coming to the program or who had undergone bariatric surgery were excluded.

Participants had a mean age of 43 years, were 86% women, were 60% White, and had a mean body mass index of 36. They were surveyed about their weekly alcohol use prior to AOM initiation and again at the time of AOM refill.

At baseline, they were divided into categories of 0 (no alcohol use; n = 6562), category 1 (one to three drinks for women and one to six for men; n = 5948), category 2 (4-6 for women and 7-14 for men; n = 1216), and category 3 (≥ 7 for women and ≥ 15 for men; n = 327).

At the second survey, 24% reported decreased drinking after starting an AOM, 71% reported no change, and 4% reported increased drinking (P < .0001). But when just the 7491 individuals who reported any alcohol use at baseline were included, 45% reported decreased drinking after starting an AOM, 52% reported no change, and only 2% reported increased drinking.

The decrease in drinking with AOM use rose with greater alcohol use at baseline, from 37% for category 1, 76% for category 2, and 91% for category 3. The proportions reporting increased drinking were just 3%, 1%, and 0%, respectively. The adjusted odds ratios (ORs) for decreasing drinking were 5.97 for category 2 (P < .0001) and 19.18 for category 3 (P < .0001) vs category 1.

The proportions reporting reduced drinking were similar across AOM classes: 51% for metformin, 46% for bupropion/naltrexone, 46% for first-generation GLP-1s (Saxenda, Trulicity, and Victoza), and 45% for the second-generation GLP-1 drugs (Mounjaro, Ozempic, Rybelsus, Wegovy, and Zepbound). All were statistically significant at P < .0001.

The highest proportion reporting increased drinking was 4% for bupropion/naltrexone. Compared with women, men were significantly more likely to report decreased drinking with AOM use (adjusted OR, 0.74; P < .001), but there were no differences by race/ethnicity or age.

Compared with those who had overweight, those in obesity classes I, II, and III were all more likely to decrease drinking with AOM use, with adjusted ORs of 1.26 (P = .0045), 1.49 (P < .001), and 1.63 (P < .001), respectively.
 

Mechanisms Appear Both Biological and Behavioral

During the discussion, Cardel said that qualitative assessments with participants suggest that there are at least two mechanisms behind this phenomenon: One biological and the other intentional.

“What we hear from them is twofold, one, particularly amongst those folks on GLP-1 medications, we’re hearing that physiologically, they feel different with the medications, that their cravings for alcohol are decreased, and that when they do choose to drink that there’s often a very much a negative reinforcement ... I’ve had a patient tell me, ‘I used to be able to have two or three margaritas, and maybe I didn’t feel like the best I’d ever felt in the morning, but I was okay. And now if I have two or three drinks, I will be throwing up for 5 hours, and it’s the worst hangover I’ve ever had in my life.’ And so it very much creates that negative reinforcement loop.”

But at the same time, “folks who are coming to us and seeking these medications are very much on a on a health-based journey. That’s what they tell us. The majority of our patients are there to improve their health. We rarely hear about the vanity or aesthetic part of it. So perhaps it’s that, in terms of trying to improve their health, they’re also trying to reduce their alcohol consumption, either just for their overall health or also as a means of trying to decrease their overall calorie consumption.”

In future research, Cardel said, “we want to examine whether the anti-obesity medications are more successful at reducing alcohol use compared to non-pharmacological weight management interventions, as we know that people often reduce their alcohol consumption on a weight management journey as a means of prioritizing their calories for food and decreasing the calories from alcohol.”

Cardel and all the study coauthors were employees and shareholders at WeightWatchers at the time the research was conducted. Skelton is editor in chief of the journal Childhood Obesity.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Several types of anti-obesity medications (AOMs), including glucagon-like peptide 1s (GLP-1s), are associated with decreased alcohol use, new research suggests.

The findings, from surveys of more than 14,000 participants in WeightWatchers’ telehealth weight management program, were presented on November 6 at the Obesity Society’s Obesity Week 2024 meeting by the company’s Chief Nutrition Officer, Michelle I. Cardel, PhD, RD, based in Gainesville, Florida.

Similar reductions in alcohol consumption were seen in people taking different classes of AOMs, suggesting “an additional mechanism by which AOMs reduce energy intake, and also signal a potential role for these medications to reduce alcohol use,” Cardel said, adding “Clinicians treating individuals for obesity may consider anti-obesity medications particularly among those who report higher alcohol intake.”

Asked to comment, session moderator and obesity researcher Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said, “I think there are some overlapping pathways there, possibly a reward system or something like that in the brain. I don’t think we know exactly what the end result will be as a potential use of the medications. But there’s a signal that needs to be investigated more.”

Cardel noted that there was one previous large cohort study finding that semaglutide was associated with a lower risk for alcohol use disorder, and another study that analyzed social media threads of people saying they’d quit drinking after starting a GLP-1 drug. But this new study is the first to examine the relationship with different classes of AOMs and to quantify the amount of alcohol consumed.
 

About Half Reported Reduced Alcohol Consumption, Regardless the AOM Class

The study included 14,053 WeightWatchers’ telehealth program participants who initiated an AOM between January 2022 and August 2023 and refilled the same AOM between October and November 2023. Those who had previously used AOMs before coming to the program or who had undergone bariatric surgery were excluded.

Participants had a mean age of 43 years, were 86% women, were 60% White, and had a mean body mass index of 36. They were surveyed about their weekly alcohol use prior to AOM initiation and again at the time of AOM refill.

At baseline, they were divided into categories of 0 (no alcohol use; n = 6562), category 1 (one to three drinks for women and one to six for men; n = 5948), category 2 (4-6 for women and 7-14 for men; n = 1216), and category 3 (≥ 7 for women and ≥ 15 for men; n = 327).

At the second survey, 24% reported decreased drinking after starting an AOM, 71% reported no change, and 4% reported increased drinking (P < .0001). But when just the 7491 individuals who reported any alcohol use at baseline were included, 45% reported decreased drinking after starting an AOM, 52% reported no change, and only 2% reported increased drinking.

The decrease in drinking with AOM use rose with greater alcohol use at baseline, from 37% for category 1, 76% for category 2, and 91% for category 3. The proportions reporting increased drinking were just 3%, 1%, and 0%, respectively. The adjusted odds ratios (ORs) for decreasing drinking were 5.97 for category 2 (P < .0001) and 19.18 for category 3 (P < .0001) vs category 1.

The proportions reporting reduced drinking were similar across AOM classes: 51% for metformin, 46% for bupropion/naltrexone, 46% for first-generation GLP-1s (Saxenda, Trulicity, and Victoza), and 45% for the second-generation GLP-1 drugs (Mounjaro, Ozempic, Rybelsus, Wegovy, and Zepbound). All were statistically significant at P < .0001.

The highest proportion reporting increased drinking was 4% for bupropion/naltrexone. Compared with women, men were significantly more likely to report decreased drinking with AOM use (adjusted OR, 0.74; P < .001), but there were no differences by race/ethnicity or age.

Compared with those who had overweight, those in obesity classes I, II, and III were all more likely to decrease drinking with AOM use, with adjusted ORs of 1.26 (P = .0045), 1.49 (P < .001), and 1.63 (P < .001), respectively.
 

Mechanisms Appear Both Biological and Behavioral

During the discussion, Cardel said that qualitative assessments with participants suggest that there are at least two mechanisms behind this phenomenon: One biological and the other intentional.

“What we hear from them is twofold, one, particularly amongst those folks on GLP-1 medications, we’re hearing that physiologically, they feel different with the medications, that their cravings for alcohol are decreased, and that when they do choose to drink that there’s often a very much a negative reinforcement ... I’ve had a patient tell me, ‘I used to be able to have two or three margaritas, and maybe I didn’t feel like the best I’d ever felt in the morning, but I was okay. And now if I have two or three drinks, I will be throwing up for 5 hours, and it’s the worst hangover I’ve ever had in my life.’ And so it very much creates that negative reinforcement loop.”

But at the same time, “folks who are coming to us and seeking these medications are very much on a on a health-based journey. That’s what they tell us. The majority of our patients are there to improve their health. We rarely hear about the vanity or aesthetic part of it. So perhaps it’s that, in terms of trying to improve their health, they’re also trying to reduce their alcohol consumption, either just for their overall health or also as a means of trying to decrease their overall calorie consumption.”

In future research, Cardel said, “we want to examine whether the anti-obesity medications are more successful at reducing alcohol use compared to non-pharmacological weight management interventions, as we know that people often reduce their alcohol consumption on a weight management journey as a means of prioritizing their calories for food and decreasing the calories from alcohol.”

Cardel and all the study coauthors were employees and shareholders at WeightWatchers at the time the research was conducted. Skelton is editor in chief of the journal Childhood Obesity.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Several types of anti-obesity medications (AOMs), including glucagon-like peptide 1s (GLP-1s), are associated with decreased alcohol use, new research suggests.

The findings, from surveys of more than 14,000 participants in WeightWatchers’ telehealth weight management program, were presented on November 6 at the Obesity Society’s Obesity Week 2024 meeting by the company’s Chief Nutrition Officer, Michelle I. Cardel, PhD, RD, based in Gainesville, Florida.

Similar reductions in alcohol consumption were seen in people taking different classes of AOMs, suggesting “an additional mechanism by which AOMs reduce energy intake, and also signal a potential role for these medications to reduce alcohol use,” Cardel said, adding “Clinicians treating individuals for obesity may consider anti-obesity medications particularly among those who report higher alcohol intake.”

Asked to comment, session moderator and obesity researcher Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said, “I think there are some overlapping pathways there, possibly a reward system or something like that in the brain. I don’t think we know exactly what the end result will be as a potential use of the medications. But there’s a signal that needs to be investigated more.”

Cardel noted that there was one previous large cohort study finding that semaglutide was associated with a lower risk for alcohol use disorder, and another study that analyzed social media threads of people saying they’d quit drinking after starting a GLP-1 drug. But this new study is the first to examine the relationship with different classes of AOMs and to quantify the amount of alcohol consumed.
 

About Half Reported Reduced Alcohol Consumption, Regardless the AOM Class

The study included 14,053 WeightWatchers’ telehealth program participants who initiated an AOM between January 2022 and August 2023 and refilled the same AOM between October and November 2023. Those who had previously used AOMs before coming to the program or who had undergone bariatric surgery were excluded.

Participants had a mean age of 43 years, were 86% women, were 60% White, and had a mean body mass index of 36. They were surveyed about their weekly alcohol use prior to AOM initiation and again at the time of AOM refill.

At baseline, they were divided into categories of 0 (no alcohol use; n = 6562), category 1 (one to three drinks for women and one to six for men; n = 5948), category 2 (4-6 for women and 7-14 for men; n = 1216), and category 3 (≥ 7 for women and ≥ 15 for men; n = 327).

At the second survey, 24% reported decreased drinking after starting an AOM, 71% reported no change, and 4% reported increased drinking (P < .0001). But when just the 7491 individuals who reported any alcohol use at baseline were included, 45% reported decreased drinking after starting an AOM, 52% reported no change, and only 2% reported increased drinking.

The decrease in drinking with AOM use rose with greater alcohol use at baseline, from 37% for category 1, 76% for category 2, and 91% for category 3. The proportions reporting increased drinking were just 3%, 1%, and 0%, respectively. The adjusted odds ratios (ORs) for decreasing drinking were 5.97 for category 2 (P < .0001) and 19.18 for category 3 (P < .0001) vs category 1.

The proportions reporting reduced drinking were similar across AOM classes: 51% for metformin, 46% for bupropion/naltrexone, 46% for first-generation GLP-1s (Saxenda, Trulicity, and Victoza), and 45% for the second-generation GLP-1 drugs (Mounjaro, Ozempic, Rybelsus, Wegovy, and Zepbound). All were statistically significant at P < .0001.

The highest proportion reporting increased drinking was 4% for bupropion/naltrexone. Compared with women, men were significantly more likely to report decreased drinking with AOM use (adjusted OR, 0.74; P < .001), but there were no differences by race/ethnicity or age.

Compared with those who had overweight, those in obesity classes I, II, and III were all more likely to decrease drinking with AOM use, with adjusted ORs of 1.26 (P = .0045), 1.49 (P < .001), and 1.63 (P < .001), respectively.
 

Mechanisms Appear Both Biological and Behavioral

During the discussion, Cardel said that qualitative assessments with participants suggest that there are at least two mechanisms behind this phenomenon: One biological and the other intentional.

“What we hear from them is twofold, one, particularly amongst those folks on GLP-1 medications, we’re hearing that physiologically, they feel different with the medications, that their cravings for alcohol are decreased, and that when they do choose to drink that there’s often a very much a negative reinforcement ... I’ve had a patient tell me, ‘I used to be able to have two or three margaritas, and maybe I didn’t feel like the best I’d ever felt in the morning, but I was okay. And now if I have two or three drinks, I will be throwing up for 5 hours, and it’s the worst hangover I’ve ever had in my life.’ And so it very much creates that negative reinforcement loop.”

But at the same time, “folks who are coming to us and seeking these medications are very much on a on a health-based journey. That’s what they tell us. The majority of our patients are there to improve their health. We rarely hear about the vanity or aesthetic part of it. So perhaps it’s that, in terms of trying to improve their health, they’re also trying to reduce their alcohol consumption, either just for their overall health or also as a means of trying to decrease their overall calorie consumption.”

In future research, Cardel said, “we want to examine whether the anti-obesity medications are more successful at reducing alcohol use compared to non-pharmacological weight management interventions, as we know that people often reduce their alcohol consumption on a weight management journey as a means of prioritizing their calories for food and decreasing the calories from alcohol.”

Cardel and all the study coauthors were employees and shareholders at WeightWatchers at the time the research was conducted. Skelton is editor in chief of the journal Childhood Obesity.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.

METHODOLOGY:

• Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
• They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
• Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
• Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
• The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.

TAKEAWAY:

• Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
• Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
• Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
• A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.

IN PRACTICE:

“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.

SOURCE:

The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.

LIMITATIONS:

The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants. 

DISCLOSURES:

This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.

METHODOLOGY:

• Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
• They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
• Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
• Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
• The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.

TAKEAWAY:

• Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
• Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
• Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
• A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.

IN PRACTICE:

“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.

SOURCE:

The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.

LIMITATIONS:

The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants. 

DISCLOSURES:

This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.

METHODOLOGY:

• Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
• They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
• Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
• Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
• The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.

TAKEAWAY:

• Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
• Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
• Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
• A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.

IN PRACTICE:

“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.

SOURCE:

The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.

LIMITATIONS:

The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants. 

DISCLOSURES:

This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

On September 27, 2024, UMC Health System in Lubbock, Texas, experienced an IT outage because of a cybersecurity incident that temporarily diverted patients to other healthcare facilities. So far, in 2024, there have been 386 cyberattacks on healthcare organizations. These high-impact ransomware attacks disrupt and delay patient care.

In recent years, many healthcare systems, including Scripps Health, Universal Health Services, Vastaamo, Sky Lakes, and the University of Vermont, have paid millions — even tens of millions — to recover data after a cyberattack or data breach. When healthcare systems come under cyber fire, the impact extends far past disrupting workflows and compromising data, patient safety can be also be compromised, vital information may be lost, and imaging and lab results can go missing or be held for ransom, making physicians’ job difficult or impossible.

In fact, cyberattacks on hospitals are far more common than you may realize. A new report issued by Ponemon and Proofpoint found that 92% of healthcare organizations have experienced a cyberattack in the past 12 months. Even more sobering is that about half of the organizations affected suffered disruptions in patient care.
 

Healthcare Systems = ‘Soft Targets’

Healthcare systems are a “soft target” for hackers for several reasons, pointed out Matthew Radolec, vice president, incident response and cloud operations at Varonis, a data security company. “One, they’re usually an amalgamation of many healthcare systems that are interconnected,” said Radolec. “A lot of hospitals are connected to other hospitals or connected to educational institutions, which means their computer vulnerabilities are shared ... and if they have an issue, it could very easily spread to your network.”

Another factor is the cost of securing data. “[With hospitals], they’ll say that a dollar spent on security is a dollar not spent on patient care,” said Radolec. “So the idea of investing in security is really tough from a budget standpoint…they’re choosing between a new MRI machine or better antivirus, backups, or data security.”

Because of the wealth of private data and healthcare information they maintain, hospitals are considered “high impact” for cybercriminals. Attackers know that if they get a foothold in a hospital, it’s more likely to pay — and pay quickly, Radolec told this news organization. Hospitals are also likely to have cyber insurance to help cover the cost of having their data stolen, encrypted, and ransomed.

The 2024 Microsoft Digital Defense Report also found that the bad actors are more sophisticated and better resourced and can challenge even the best cybersecurity. Improved defenses may not be good enough, and the sheer volume of attacks must be met with effective deterrence and government solutions that impose consequences for cybercriminals.
 

Vulnerable Users

Whether through a phishing email or text, password attack, or web attack, “the moment a ‘threat actor’ gets into your institution and gets credentials ... that’s the Nirvana state of a threat actor,” warned Ryan Witt, chair of the healthcare customer advisory board and vice president of Industry Solutions at Proofpoint, a cybersecurity platform. “They have those credentials and will go into deep reconnaissance mode. It often takes healthcare up to 6 months to even ascertain whether somebody’s actually in the network.” During that time, the hacker is learning how the institution works, what job functions matter, and how best to plan their attack.

“Attackers are getting in because they’re buying databases of usernames and passwords. And they’re trying them by the millions,” added Radolec. “For a sophisticated actor, all it takes is time and motivation. They have the skills. It’s just a matter of how persistent they want to be.”

Certain hospital staff are also more likely to be targeted by cyberhackers than others. “About 10% of a healthcare organization’s user base is much more vulnerable for all sorts of reasons — how they work, the value of their job title and job function, and therefore their access to systems,” said Witt.

High-profile staff are more likely to be targeted than those in lower-level positions; the so-called “CEO attack” is typical. However, staff in other hospital departments are also subject to cybercriminals, including hospice departments/hospice organizations and research arms of hospitals.
 

The Impact of Cyberattacks on Patients 

Physicians and healthcare execs may have considered cybersecurity more of a compliance issue than a true threat to patients in the past. But this attitude is rapidly changing. “We are starting to see a very clear connection between a cyber event and how it can impact patient care and patient safety,” said Witt.

According to the Proofpoint report, cyber breaches can severely affect patient care. In 2024:

• 56% of respondents saw a delay in patient tests/procedures
• 53% experienced increased patient complications from medical procedures
• 52% noted a longer patient length of stay
• 44% saw an increase in patient transfers to other facilities
• 28% had an increase in mortality rate

What Hospitals and Physicians Can Do

Fortunately, hospitals can take measures to better protect their data and their patients. One strategy is segmenting networks to reduce the amount of data or systems one person or system can access. Educating staff about the dangers of phishing and spoofing emails also help protect organizations from ransomware attacks. Having staff avoid reusing passwords and updating logins and passwords frequently helps.

Most hospitals also need more robust security controls. Physicians and healthcare facilities must also embrace the cybersecurity controls found in other industries, said Witt. “Multifactor authentication is one of those things that can cause us frustration,” he said. “The controls can seem onerous, but they’re really valuable overall…and should become standard practice.”

Doctors can also prepare for a ransomware attack and protect patients by practicing some “old-school” medicine, like using paper systems and maintaining good patient notes — often, those notes are synced locally as well as offsite, so you’d be able to access them even during a data breach. “It’s smart to write prescriptions on pads sometimes,” said Radolec. “Don’t forget how to do those things because that will make you more resilient in the event of a ransomware attack.”
 

A Continuing Threat

Cyberattacks will continue. “When you look at the high likelihood [of success] and the soft target, you end up with ... a perfect storm,” said Radolec. “Hospitals have a lot of vulnerabilities. They have to keep operations going just to receive income, but also to deliver care to people.”

That means that the burden is on healthcare organizations — including physicians, nurses, staff, and C-level execs — to help keep the “security” in cybersecurity. “We are all part of the cybersecurity defense,” said Witt. Helping to maintain that defense has become a critical aspect of caring for patients.

A version of this article first appeared on Medscape.com.

On September 27, 2024, UMC Health System in Lubbock, Texas, experienced an IT outage because of a cybersecurity incident that temporarily diverted patients to other healthcare facilities. So far, in 2024, there have been 386 cyberattacks on healthcare organizations. These high-impact ransomware attacks disrupt and delay patient care.

In recent years, many healthcare systems, including Scripps Health, Universal Health Services, Vastaamo, Sky Lakes, and the University of Vermont, have paid millions — even tens of millions — to recover data after a cyberattack or data breach. When healthcare systems come under cyber fire, the impact extends far past disrupting workflows and compromising data, patient safety can be also be compromised, vital information may be lost, and imaging and lab results can go missing or be held for ransom, making physicians’ job difficult or impossible.

In fact, cyberattacks on hospitals are far more common than you may realize. A new report issued by Ponemon and Proofpoint found that 92% of healthcare organizations have experienced a cyberattack in the past 12 months. Even more sobering is that about half of the organizations affected suffered disruptions in patient care.
 

Healthcare Systems = ‘Soft Targets’

Healthcare systems are a “soft target” for hackers for several reasons, pointed out Matthew Radolec, vice president, incident response and cloud operations at Varonis, a data security company. “One, they’re usually an amalgamation of many healthcare systems that are interconnected,” said Radolec. “A lot of hospitals are connected to other hospitals or connected to educational institutions, which means their computer vulnerabilities are shared ... and if they have an issue, it could very easily spread to your network.”

Another factor is the cost of securing data. “[With hospitals], they’ll say that a dollar spent on security is a dollar not spent on patient care,” said Radolec. “So the idea of investing in security is really tough from a budget standpoint…they’re choosing between a new MRI machine or better antivirus, backups, or data security.”

Because of the wealth of private data and healthcare information they maintain, hospitals are considered “high impact” for cybercriminals. Attackers know that if they get a foothold in a hospital, it’s more likely to pay — and pay quickly, Radolec told this news organization. Hospitals are also likely to have cyber insurance to help cover the cost of having their data stolen, encrypted, and ransomed.

The 2024 Microsoft Digital Defense Report also found that the bad actors are more sophisticated and better resourced and can challenge even the best cybersecurity. Improved defenses may not be good enough, and the sheer volume of attacks must be met with effective deterrence and government solutions that impose consequences for cybercriminals.
 

Vulnerable Users

Whether through a phishing email or text, password attack, or web attack, “the moment a ‘threat actor’ gets into your institution and gets credentials ... that’s the Nirvana state of a threat actor,” warned Ryan Witt, chair of the healthcare customer advisory board and vice president of Industry Solutions at Proofpoint, a cybersecurity platform. “They have those credentials and will go into deep reconnaissance mode. It often takes healthcare up to 6 months to even ascertain whether somebody’s actually in the network.” During that time, the hacker is learning how the institution works, what job functions matter, and how best to plan their attack.

“Attackers are getting in because they’re buying databases of usernames and passwords. And they’re trying them by the millions,” added Radolec. “For a sophisticated actor, all it takes is time and motivation. They have the skills. It’s just a matter of how persistent they want to be.”

Certain hospital staff are also more likely to be targeted by cyberhackers than others. “About 10% of a healthcare organization’s user base is much more vulnerable for all sorts of reasons — how they work, the value of their job title and job function, and therefore their access to systems,” said Witt.

High-profile staff are more likely to be targeted than those in lower-level positions; the so-called “CEO attack” is typical. However, staff in other hospital departments are also subject to cybercriminals, including hospice departments/hospice organizations and research arms of hospitals.
 

The Impact of Cyberattacks on Patients 

Physicians and healthcare execs may have considered cybersecurity more of a compliance issue than a true threat to patients in the past. But this attitude is rapidly changing. “We are starting to see a very clear connection between a cyber event and how it can impact patient care and patient safety,” said Witt.

According to the Proofpoint report, cyber breaches can severely affect patient care. In 2024:

• 56% of respondents saw a delay in patient tests/procedures
• 53% experienced increased patient complications from medical procedures
• 52% noted a longer patient length of stay
• 44% saw an increase in patient transfers to other facilities
• 28% had an increase in mortality rate

What Hospitals and Physicians Can Do

Fortunately, hospitals can take measures to better protect their data and their patients. One strategy is segmenting networks to reduce the amount of data or systems one person or system can access. Educating staff about the dangers of phishing and spoofing emails also help protect organizations from ransomware attacks. Having staff avoid reusing passwords and updating logins and passwords frequently helps.

Most hospitals also need more robust security controls. Physicians and healthcare facilities must also embrace the cybersecurity controls found in other industries, said Witt. “Multifactor authentication is one of those things that can cause us frustration,” he said. “The controls can seem onerous, but they’re really valuable overall…and should become standard practice.”

Doctors can also prepare for a ransomware attack and protect patients by practicing some “old-school” medicine, like using paper systems and maintaining good patient notes — often, those notes are synced locally as well as offsite, so you’d be able to access them even during a data breach. “It’s smart to write prescriptions on pads sometimes,” said Radolec. “Don’t forget how to do those things because that will make you more resilient in the event of a ransomware attack.”
 

A Continuing Threat

Cyberattacks will continue. “When you look at the high likelihood [of success] and the soft target, you end up with ... a perfect storm,” said Radolec. “Hospitals have a lot of vulnerabilities. They have to keep operations going just to receive income, but also to deliver care to people.”

That means that the burden is on healthcare organizations — including physicians, nurses, staff, and C-level execs — to help keep the “security” in cybersecurity. “We are all part of the cybersecurity defense,” said Witt. Helping to maintain that defense has become a critical aspect of caring for patients.

A version of this article first appeared on Medscape.com.

On September 27, 2024, UMC Health System in Lubbock, Texas, experienced an IT outage because of a cybersecurity incident that temporarily diverted patients to other healthcare facilities. So far, in 2024, there have been 386 cyberattacks on healthcare organizations. These high-impact ransomware attacks disrupt and delay patient care.

In recent years, many healthcare systems, including Scripps Health, Universal Health Services, Vastaamo, Sky Lakes, and the University of Vermont, have paid millions — even tens of millions — to recover data after a cyberattack or data breach. When healthcare systems come under cyber fire, the impact extends far past disrupting workflows and compromising data, patient safety can be also be compromised, vital information may be lost, and imaging and lab results can go missing or be held for ransom, making physicians’ job difficult or impossible.

In fact, cyberattacks on hospitals are far more common than you may realize. A new report issued by Ponemon and Proofpoint found that 92% of healthcare organizations have experienced a cyberattack in the past 12 months. Even more sobering is that about half of the organizations affected suffered disruptions in patient care.
 

Healthcare Systems = ‘Soft Targets’

Healthcare systems are a “soft target” for hackers for several reasons, pointed out Matthew Radolec, vice president, incident response and cloud operations at Varonis, a data security company. “One, they’re usually an amalgamation of many healthcare systems that are interconnected,” said Radolec. “A lot of hospitals are connected to other hospitals or connected to educational institutions, which means their computer vulnerabilities are shared ... and if they have an issue, it could very easily spread to your network.”

Another factor is the cost of securing data. “[With hospitals], they’ll say that a dollar spent on security is a dollar not spent on patient care,” said Radolec. “So the idea of investing in security is really tough from a budget standpoint…they’re choosing between a new MRI machine or better antivirus, backups, or data security.”

Because of the wealth of private data and healthcare information they maintain, hospitals are considered “high impact” for cybercriminals. Attackers know that if they get a foothold in a hospital, it’s more likely to pay — and pay quickly, Radolec told this news organization. Hospitals are also likely to have cyber insurance to help cover the cost of having their data stolen, encrypted, and ransomed.

The 2024 Microsoft Digital Defense Report also found that the bad actors are more sophisticated and better resourced and can challenge even the best cybersecurity. Improved defenses may not be good enough, and the sheer volume of attacks must be met with effective deterrence and government solutions that impose consequences for cybercriminals.
 

Vulnerable Users

Whether through a phishing email or text, password attack, or web attack, “the moment a ‘threat actor’ gets into your institution and gets credentials ... that’s the Nirvana state of a threat actor,” warned Ryan Witt, chair of the healthcare customer advisory board and vice president of Industry Solutions at Proofpoint, a cybersecurity platform. “They have those credentials and will go into deep reconnaissance mode. It often takes healthcare up to 6 months to even ascertain whether somebody’s actually in the network.” During that time, the hacker is learning how the institution works, what job functions matter, and how best to plan their attack.

“Attackers are getting in because they’re buying databases of usernames and passwords. And they’re trying them by the millions,” added Radolec. “For a sophisticated actor, all it takes is time and motivation. They have the skills. It’s just a matter of how persistent they want to be.”

Certain hospital staff are also more likely to be targeted by cyberhackers than others. “About 10% of a healthcare organization’s user base is much more vulnerable for all sorts of reasons — how they work, the value of their job title and job function, and therefore their access to systems,” said Witt.

High-profile staff are more likely to be targeted than those in lower-level positions; the so-called “CEO attack” is typical. However, staff in other hospital departments are also subject to cybercriminals, including hospice departments/hospice organizations and research arms of hospitals.
 

The Impact of Cyberattacks on Patients 

Physicians and healthcare execs may have considered cybersecurity more of a compliance issue than a true threat to patients in the past. But this attitude is rapidly changing. “We are starting to see a very clear connection between a cyber event and how it can impact patient care and patient safety,” said Witt.

According to the Proofpoint report, cyber breaches can severely affect patient care. In 2024:

• 56% of respondents saw a delay in patient tests/procedures
• 53% experienced increased patient complications from medical procedures
• 52% noted a longer patient length of stay
• 44% saw an increase in patient transfers to other facilities
• 28% had an increase in mortality rate

What Hospitals and Physicians Can Do

Fortunately, hospitals can take measures to better protect their data and their patients. One strategy is segmenting networks to reduce the amount of data or systems one person or system can access. Educating staff about the dangers of phishing and spoofing emails also help protect organizations from ransomware attacks. Having staff avoid reusing passwords and updating logins and passwords frequently helps.

Most hospitals also need more robust security controls. Physicians and healthcare facilities must also embrace the cybersecurity controls found in other industries, said Witt. “Multifactor authentication is one of those things that can cause us frustration,” he said. “The controls can seem onerous, but they’re really valuable overall…and should become standard practice.”

Doctors can also prepare for a ransomware attack and protect patients by practicing some “old-school” medicine, like using paper systems and maintaining good patient notes — often, those notes are synced locally as well as offsite, so you’d be able to access them even during a data breach. “It’s smart to write prescriptions on pads sometimes,” said Radolec. “Don’t forget how to do those things because that will make you more resilient in the event of a ransomware attack.”
 

A Continuing Threat

Cyberattacks will continue. “When you look at the high likelihood [of success] and the soft target, you end up with ... a perfect storm,” said Radolec. “Hospitals have a lot of vulnerabilities. They have to keep operations going just to receive income, but also to deliver care to people.”

That means that the burden is on healthcare organizations — including physicians, nurses, staff, and C-level execs — to help keep the “security” in cybersecurity. “We are all part of the cybersecurity defense,” said Witt. Helping to maintain that defense has become a critical aspect of caring for patients.

A version of this article first appeared on Medscape.com.

When psychiatrist Paul Sartain, MD (not his real name), received a letter from his state’s medical board, he was concerned. A patient’s family complained that he made sexual advances to a young woman he treated for psychotic depression.

“There was absolutely no evidence, and the claims were vague,” he said. “I think the family was angry at me and with the system — the woman had not gotten better.” Sartain reviewed his medical records and then called his malpractice insurer.

The insurer asked about his involvement with the patient’s case, if there was anything credible to the patient’s complaint, and if he had thorough documentation. Then, the carrier offered Sartain his choice of several attorneys who could represent him. The medical board ultimately closed the case with no findings against him, and the patient’s family never sued him.

While Sartain said he trusted his carrier-provided attorney, he would have considered hiring his own attorney as well if a criminal issue was also alleged.

“If I’m wrongly accused, I’m defended (by the carrier). If I had stolen money or had a sexual relationship with the patient, then you’re acting outside the bounds of what is protected (by the carrier),” he said.
 

How Medical Board and Malpractice Insurer Investigations Differ

Medical board complaints differ from malpractice claims, in which patients seek damages. The investigation process also varies.

When a patient reports a doctor to a state medical board, they may also sue the doctor for monetary damages in civil court. The medical board responds to patient complaints made directly to them, but it also may also initiate its own investigations. Those can be prompted by a malpractice claim resolution, with a court verdict against the doctor, or a settlement recorded in the National Practitioner Data Bank.

Malpractice insurers may offer limited legal representation for medical board investigations, requiring the doctor to report the medical board issue to them before the doctor takes any action. Often, they will cover up to $50,000 in defense costs but not cover any subsequent medical board fines or required classes or medical board fees.

When a doctor contacts the carrier about a medical board investigation, the carrier may ask for the medical board document and the medical records, said Alex Keoskey, a partner in Frier Levitt’s life sciences group.

The carrier may want to ask about the patient, staff members involved, the doctor’s background, if there have been previous medical board investigations or lawsuits against this doctor, and the doctor’s opinion of the allegations. The doctor should be transparent with the carrier, Keoskey said.

Some carriers conduct more in-depth investigations, examining record-keeping, prescription practices, patient consent processes, and continuing medical education status. That’s because the medical board may inquire about these as well should its own investigation expand.

Not all carriers explore cases like these, even if reimbursing for defense costs, said Karen Frisella, director of professional liability claims at BETA Healthcare Group in California. In her experience, a licensing investigation usually follows a claim resolution that was already worked up by the carrier. If a complaint was made directly to the licensing board without an accompanying liability claim, the carrier’s ability to initiate an investigation on the incident depends on the policy terms or coverage available.

“Typically, a professional liability policy requires that the insured report a claim to trigger coverage. The carrier can’t unilaterally decide to open a claim,” she said. A licensing board investigation is not a claim by definition and therefore does not provide a mechanism for the carrier to open a liability claim file, she added.

If the medical board ultimately restricts the doctor’s license or puts the doctor on probation, that becomes public, and the underwriting department may then look into it.

Malpractice insurers routinely monitor licensing board discipline notices. A reprimand or restrictions on a doctor’s license could trigger a review of the physician’s future insurability and lead to higher premiums or even nonrenewal, Frisella said.

If a carrier investigates a reported claim and determines there are issues with the care rendered, whether there is an accompanying medical board action, that also can affect underwriting decisions, Frisella said.
 

Who Is Your Attorney Really Working for?

The doctor should understand whose interests the attorney represents. In a medical board claim, the attorney — even if defense is paid by the carrier — represents the doctor.

Frisella said her organization provides pass-through coverage, meaning it reimburses the doctor for medical board defense costs. “Because the carrier isn’t directing the medical board defense, it is not generally privy to the work product.”

If a patient files a malpractice claim, however, the attorney ultimately represents the insurance company.

“The panel counsel who works for the insurer does not work for the doctor, and that’s always important to remember,” Keoskey said. While the attorney will do their best to aggressively defend the doctor, “he’s going to protect the insurer’s interest before the doctor’s.”

Physicians who find any conflict of interest with their insurer should seek counsel.

Such conflicts could include:

• Disagreements over the case’s ultimate worth. For example, a physician might want a case to settle for less than their carrier is willing to pay.
• The legal judgment may exceed the carrier’s policy limits, or there are punitive damages or allegations of criminal acts that the insurer does not cover.

In these cases, the insurance company should recommend the doctor get personal counsel. They will send a reservation of rights letter saying they will defend the doctor for now, but if the facts show the doctor committed some type of misconduct, they may decline coverage, said Keoskey. Some states, including California, require that the carrier pay for this independent counsel.

Unless there is a conflict of interest, though, having a personal attorney just makes the situation more complicated, said Frisella.

A version of this article first appeared on Medscape.com.

When psychiatrist Paul Sartain, MD (not his real name), received a letter from his state’s medical board, he was concerned. A patient’s family complained that he made sexual advances to a young woman he treated for psychotic depression.

“There was absolutely no evidence, and the claims were vague,” he said. “I think the family was angry at me and with the system — the woman had not gotten better.” Sartain reviewed his medical records and then called his malpractice insurer.

The insurer asked about his involvement with the patient’s case, if there was anything credible to the patient’s complaint, and if he had thorough documentation. Then, the carrier offered Sartain his choice of several attorneys who could represent him. The medical board ultimately closed the case with no findings against him, and the patient’s family never sued him.

While Sartain said he trusted his carrier-provided attorney, he would have considered hiring his own attorney as well if a criminal issue was also alleged.

“If I’m wrongly accused, I’m defended (by the carrier). If I had stolen money or had a sexual relationship with the patient, then you’re acting outside the bounds of what is protected (by the carrier),” he said.
 

How Medical Board and Malpractice Insurer Investigations Differ

Medical board complaints differ from malpractice claims, in which patients seek damages. The investigation process also varies.

When a patient reports a doctor to a state medical board, they may also sue the doctor for monetary damages in civil court. The medical board responds to patient complaints made directly to them, but it also may also initiate its own investigations. Those can be prompted by a malpractice claim resolution, with a court verdict against the doctor, or a settlement recorded in the National Practitioner Data Bank.

Malpractice insurers may offer limited legal representation for medical board investigations, requiring the doctor to report the medical board issue to them before the doctor takes any action. Often, they will cover up to $50,000 in defense costs but not cover any subsequent medical board fines or required classes or medical board fees.

When a doctor contacts the carrier about a medical board investigation, the carrier may ask for the medical board document and the medical records, said Alex Keoskey, a partner in Frier Levitt’s life sciences group.

The carrier may want to ask about the patient, staff members involved, the doctor’s background, if there have been previous medical board investigations or lawsuits against this doctor, and the doctor’s opinion of the allegations. The doctor should be transparent with the carrier, Keoskey said.

Some carriers conduct more in-depth investigations, examining record-keeping, prescription practices, patient consent processes, and continuing medical education status. That’s because the medical board may inquire about these as well should its own investigation expand.

Not all carriers explore cases like these, even if reimbursing for defense costs, said Karen Frisella, director of professional liability claims at BETA Healthcare Group in California. In her experience, a licensing investigation usually follows a claim resolution that was already worked up by the carrier. If a complaint was made directly to the licensing board without an accompanying liability claim, the carrier’s ability to initiate an investigation on the incident depends on the policy terms or coverage available.

“Typically, a professional liability policy requires that the insured report a claim to trigger coverage. The carrier can’t unilaterally decide to open a claim,” she said. A licensing board investigation is not a claim by definition and therefore does not provide a mechanism for the carrier to open a liability claim file, she added.

If the medical board ultimately restricts the doctor’s license or puts the doctor on probation, that becomes public, and the underwriting department may then look into it.

Malpractice insurers routinely monitor licensing board discipline notices. A reprimand or restrictions on a doctor’s license could trigger a review of the physician’s future insurability and lead to higher premiums or even nonrenewal, Frisella said.

If a carrier investigates a reported claim and determines there are issues with the care rendered, whether there is an accompanying medical board action, that also can affect underwriting decisions, Frisella said.
 

Who Is Your Attorney Really Working for?

The doctor should understand whose interests the attorney represents. In a medical board claim, the attorney — even if defense is paid by the carrier — represents the doctor.

Frisella said her organization provides pass-through coverage, meaning it reimburses the doctor for medical board defense costs. “Because the carrier isn’t directing the medical board defense, it is not generally privy to the work product.”

If a patient files a malpractice claim, however, the attorney ultimately represents the insurance company.

“The panel counsel who works for the insurer does not work for the doctor, and that’s always important to remember,” Keoskey said. While the attorney will do their best to aggressively defend the doctor, “he’s going to protect the insurer’s interest before the doctor’s.”

Physicians who find any conflict of interest with their insurer should seek counsel.

Such conflicts could include:

• Disagreements over the case’s ultimate worth. For example, a physician might want a case to settle for less than their carrier is willing to pay.
• The legal judgment may exceed the carrier’s policy limits, or there are punitive damages or allegations of criminal acts that the insurer does not cover.

In these cases, the insurance company should recommend the doctor get personal counsel. They will send a reservation of rights letter saying they will defend the doctor for now, but if the facts show the doctor committed some type of misconduct, they may decline coverage, said Keoskey. Some states, including California, require that the carrier pay for this independent counsel.

Unless there is a conflict of interest, though, having a personal attorney just makes the situation more complicated, said Frisella.

A version of this article first appeared on Medscape.com.

When psychiatrist Paul Sartain, MD (not his real name), received a letter from his state’s medical board, he was concerned. A patient’s family complained that he made sexual advances to a young woman he treated for psychotic depression.

“There was absolutely no evidence, and the claims were vague,” he said. “I think the family was angry at me and with the system — the woman had not gotten better.” Sartain reviewed his medical records and then called his malpractice insurer.

The insurer asked about his involvement with the patient’s case, if there was anything credible to the patient’s complaint, and if he had thorough documentation. Then, the carrier offered Sartain his choice of several attorneys who could represent him. The medical board ultimately closed the case with no findings against him, and the patient’s family never sued him.

While Sartain said he trusted his carrier-provided attorney, he would have considered hiring his own attorney as well if a criminal issue was also alleged.

“If I’m wrongly accused, I’m defended (by the carrier). If I had stolen money or had a sexual relationship with the patient, then you’re acting outside the bounds of what is protected (by the carrier),” he said.
 

How Medical Board and Malpractice Insurer Investigations Differ

Medical board complaints differ from malpractice claims, in which patients seek damages. The investigation process also varies.

When a patient reports a doctor to a state medical board, they may also sue the doctor for monetary damages in civil court. The medical board responds to patient complaints made directly to them, but it also may also initiate its own investigations. Those can be prompted by a malpractice claim resolution, with a court verdict against the doctor, or a settlement recorded in the National Practitioner Data Bank.

Malpractice insurers may offer limited legal representation for medical board investigations, requiring the doctor to report the medical board issue to them before the doctor takes any action. Often, they will cover up to $50,000 in defense costs but not cover any subsequent medical board fines or required classes or medical board fees.

When a doctor contacts the carrier about a medical board investigation, the carrier may ask for the medical board document and the medical records, said Alex Keoskey, a partner in Frier Levitt’s life sciences group.

The carrier may want to ask about the patient, staff members involved, the doctor’s background, if there have been previous medical board investigations or lawsuits against this doctor, and the doctor’s opinion of the allegations. The doctor should be transparent with the carrier, Keoskey said.

Some carriers conduct more in-depth investigations, examining record-keeping, prescription practices, patient consent processes, and continuing medical education status. That’s because the medical board may inquire about these as well should its own investigation expand.

Not all carriers explore cases like these, even if reimbursing for defense costs, said Karen Frisella, director of professional liability claims at BETA Healthcare Group in California. In her experience, a licensing investigation usually follows a claim resolution that was already worked up by the carrier. If a complaint was made directly to the licensing board without an accompanying liability claim, the carrier’s ability to initiate an investigation on the incident depends on the policy terms or coverage available.

“Typically, a professional liability policy requires that the insured report a claim to trigger coverage. The carrier can’t unilaterally decide to open a claim,” she said. A licensing board investigation is not a claim by definition and therefore does not provide a mechanism for the carrier to open a liability claim file, she added.

If the medical board ultimately restricts the doctor’s license or puts the doctor on probation, that becomes public, and the underwriting department may then look into it.

Malpractice insurers routinely monitor licensing board discipline notices. A reprimand or restrictions on a doctor’s license could trigger a review of the physician’s future insurability and lead to higher premiums or even nonrenewal, Frisella said.

If a carrier investigates a reported claim and determines there are issues with the care rendered, whether there is an accompanying medical board action, that also can affect underwriting decisions, Frisella said.
 

Who Is Your Attorney Really Working for?

The doctor should understand whose interests the attorney represents. In a medical board claim, the attorney — even if defense is paid by the carrier — represents the doctor.

Frisella said her organization provides pass-through coverage, meaning it reimburses the doctor for medical board defense costs. “Because the carrier isn’t directing the medical board defense, it is not generally privy to the work product.”

If a patient files a malpractice claim, however, the attorney ultimately represents the insurance company.

“The panel counsel who works for the insurer does not work for the doctor, and that’s always important to remember,” Keoskey said. While the attorney will do their best to aggressively defend the doctor, “he’s going to protect the insurer’s interest before the doctor’s.”

Physicians who find any conflict of interest with their insurer should seek counsel.

Such conflicts could include:

• Disagreements over the case’s ultimate worth. For example, a physician might want a case to settle for less than their carrier is willing to pay.
• The legal judgment may exceed the carrier’s policy limits, or there are punitive damages or allegations of criminal acts that the insurer does not cover.

In these cases, the insurance company should recommend the doctor get personal counsel. They will send a reservation of rights letter saying they will defend the doctor for now, but if the facts show the doctor committed some type of misconduct, they may decline coverage, said Keoskey. Some states, including California, require that the carrier pay for this independent counsel.

Unless there is a conflict of interest, though, having a personal attorney just makes the situation more complicated, said Frisella.

A version of this article first appeared on Medscape.com.