SAN DIEGO – A single baseline measurement of dehydroepiandrosterone sulfate (DHEAS) outperforms overnight dexamethasone suppression and other standard tests for the detection of subclinical hypercortisolism in patients with adrenal incidentalomas, according to a prospective, blinded study of 185 consecutive patients at Cambridge University in England.
It’s an important finding because 1-mg overnight dexamethasone suppression testing is the current screening standard for detection of the condition, said Dr. Michael Dennedy, a former endocrinology fellow at Cambridge and now a senior lecturer at the National University of Ireland (NUI), Galway.
“On the basis of these data, we advocate the use of a single measurement of DHEAS as a convenient, reliable, and robust test for screening of SH [subclinical hypercortisolism] in the context of adrenal incidentalomas,” Dr. Dennedy said at the meeting of the Endocrine Society.
DHEAS avoids the sampling problems and high false positives of older tests and “reliably differentiates between SH and non-SH etiologies of adrenal nodules. We use it now as a standard test for patients who have adrenal nodules” at Cambridge and NUI Galway, he said.
The theory for checking DHEAS is straightforward. Like DHEA, it’s regulated by pituitary ACTH; sustained suppression of central ACTH leads to reductions in both. However, DHEA does not work for screening because it has a short half-life – about 25 minutes – and has circadian secretion patterns similar to ACTH. The half-life of DHEAS, on the other hand, is 10-16 hours and levels stay relatively stable throughout the day, which makes it a more attractive marker for detecting chronically suppressed ACTH.
At baseline, the team measured DHEAS by immunoassay and then put their 185 subjects through standard workups for newly diagnosed adrenal incidentalomas, including plasma metanephrines, 1-mg overnight dexamethasone suppression, 24-hour urinary free cortisol, and paired renin and aldosterone measurements. They then unblinded their DHEAS measurements to see how they fared against the standard approaches.
Because DHEAS levels are determined by a person’s age and gender, the investigators used a ratio of the actual baseline measurement divided by the lower limit of the appropriate reference range; for instance, 1.2 mmol/L in younger patients and 0.4 mmol/L in older patients.
A baseline DHEAS ratio at or below 1.12 was 100% sensitive and 92% specific for the diagnosis of SH in patients with adrenal incidentalomas. In contrast, a cortisol cutoff of 1.9 mcg/dL following 1-mg dexamethasone suppression was 100% sensitive but 82.9% specific and 24-hour urinary free cortisol was 69% sensitive and 68% specific.
The patients were aged 25 years to over 85, with an average age of about 65 years; 29 (16%) were diagnosed with SH. Most had nonfunctional adenomas, and a few had adrenal cortical carcinomas.
“Once upon a time, if there was a positive overnight dexamethasone or a positive urinary free cortisol, or both, we would send” patients on for a full inpatient Cushing’s workup. “Now we have a third criterion,” he said: suppressed DHEAS. Also, “in the presence of a high DHEAS with a failed dexamethasone suppression test, you would worry about adrenal corticocarcinoma, pituitary Cushing’s, or adrenal metastasis,” Dr. Dennedy said.
The investigators had no relevant disclosures, and there was no outside funding for the research.