Applied Evidence

Subclinical hypothyroidism: Let the evidence be your guide

Author and Disclosure Information

Patient age, time of day, and supplement use influence screening results; repeat testing is advised. Avoid treating to improve mood, cognition, fatigue, or quality of life.


› Do not routinely screen for subclinical or overt hypothyroidism in asymptomatic nonpregnant adults. B

› Consider treatment of known or screening-detected subclinical hypothyroidism (SCH) in patients who are pregnant or trying to conceive. C

› Consider treating SCH in younger adults whose thyroidstimulating hormone level is ≥ 10 mIU/L. C

Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series



Subclinical hypothyroidism (SCH) is a biochemical state in which the thyroid-stimulating hormone (TSH) is elevated while the free thyroxine (T4) level is normal. Overt hypothyroidism is not diagnosed until the free T4 level is decreased, regardless of the degree of TSH elevation.

The overall prevalence of SCH in iodine-rich areas is 4% to 10%, with a risk for progression to overt hypothyroidism of between 2% and 6% annually.1 The prevalence of SCH varies depending on the TSH reference range used.1 The normal reference range for TSH varies depending on the laboratory and/or the reference population surveyed, with the range likely widening with increasing age.

SCH is most common among women, the elderly, and White individuals.2 The discovery of SCH is often incidental, given that usually it is detected by laboratory findings alone without associated symptoms of overt hypothyroidism.3

The not-so-significant role of symptoms in subclinical hypothyroidism

Symptoms associated with overt hypothyroidism include constipation, dry skin, fatigue, slow thinking, poor memory, muscle cramps, weakness, and cold intolerance. In SCH, these symptoms are inconsistent, with around 1 in 3 patients having no symptoms at all.4

One study reported that roughly 18% of euthyroid individuals, 22% of SCH patients, and 26% of those with overt hypothyroidism reported 4 or more symptoms classically thought to be related to hypothyroidism.4 A large Danish cohort study found that hypothyroid symptoms were no more common in patients with SCH than in euthyroid individuals in the general population.5 These studies question the validity of attributing symptoms to SCH.

Adverse health associations

Observational data suggest that SCH is associated with an increased risk for dyslipidemia, coronary heart disease, heart failure, and cardiovascular mortality, particularly in those with TSH levels ≥ 10 mIU/L.6,7 Such associations were not found for most adults with TSH levels between 5 and 10 mIU/L.8 There are also potential associations of SCH with obesity, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis.9,10 Despite thyroid studies being commonly ordered as part of a mental health evaluation, SCH has not been statistically associated with depressive symptoms.11,12

Caveats with laboratory testing

There are several issues to consider when performing a laboratory assessment of thyroid function. TSH levels fluctuate considerably during the day, as TSH secretion has a circadian rhythm. TSH values are 50% higher at night and in the early morning than during the rest of the day.13 TSH values also may rise in response to current illness or stress. Due to this biologic variability, repeat testing to confirm TSH levels is recommended if an initial test result is abnormal.14

Continue to: An exact reference range...


Recommended Reading

TikTok offers to ‘balance your hormones’ are pure hokum
MDedge Family Medicine
Parathyroidectomy does not preserve kidney function in seniors
MDedge Family Medicine
Seasonal variation in thyroid hormone TSH may lead to overprescribing
MDedge Family Medicine
Medications provide best risk-to-benefit ratio for weight loss, says expert
MDedge Family Medicine
Expert discusses which diets are best, based on the evidence
MDedge Family Medicine
Statin misinformation on social media flagged by AI
MDedge Family Medicine
Boys may carry the weight, or overweight, of adults’ infertility
MDedge Family Medicine
Early gestational diabetes treatment may improve neonatal outcomes
MDedge Family Medicine
BMI has greater impact on survival in younger breast cancer patients
MDedge Family Medicine
Statins appear to guard against liver disease progression
MDedge Family Medicine