Clinical Pearls & Morning Reports
Subclinical hypothyroidism is biochemically defined as an elevated serum thyrotropin level in combination with a serum free T4 level that is within the population reference range. Although many patients with subclinical hypothyroidism are asymptomatic, such patients tend to report symptoms of overt hypothyroidism more often than age-matched controls; these symptoms are usually milder than those in patients with overt hypothyroidism and tend to increase in both number and severity with higher thyrotropin levels. Read the latest Clinical Practice review on this topic.
Q. What is the risk that subclinical hypothyroidism will progress to overt hypothyroidism?
A. The risk of progression of subclinical hypothyroidism to overt hypothyroidism is approximately 2 to 6% per year; the risk is higher among women than among men and among persons with higher thyrotropin levels, those with higher levels of antibodies to thyroid peroxidase, and those with low-normal free T4 levels. Among persons who have a single elevated thyrotropin measurement of less than 7 mIU per liter, the thyrotropin level normalizes in up to 46% within 2 years.
Q. Are there long-term consequences associated with subclinical hypothyroidism?
A. Concern exists regarding the long-term adverse effects of subclinical hypothyroidism, particularly with respect to the risk of cardiovascular disease. Subclinical hypothyroidism, particularly among persons with thyrotropin levels of more than 7 mIU per liter, has been associated with increased risks of congestive heart failure and fatal stroke in meta-analyses based on individual participant data. It is unclear whether ameliorating cardiovascular risk factors with the use of levothyroxine treatment will decrease the risk of cardiovascular events.
A: Because multiple factors, such as subacute thyroiditis, recovery from a nonthyroidal illness, and medication (e.g., amiodarone and lithium), can cause transient abnormalities in the serum thyrotropin level, a transient increase in the thyrotropin level should be ruled out before a diagnosis of subclinical hypothyroidism is made. At least one repeat measurement of thyrotropin and free T4 is indicated, together with a test for antibodies to thyroid peroxidase, after a 2-to-3-month interval. Although a hypoechoic or inhomogeneous pattern on ultrasound examination of the thyroid may provide additional evidence of thyroid autoimmunity, ultrasonography is not recommended routinely for the evaluation of subclinical hypothyroidism.
A: In general, data suggest that levothyroxine treatment is unlikely to reduce symptoms in persons with modest elevations in thyrotropin levels and with minimal symptoms at baseline, but such treatment may have benefit in symptomatic patients, particularly in those who have a serum thyrotropin level above 10 to 12 mIU per liter. Treatment is generally recommended for persons 70 years of age or younger who have thyrotropin levels of 10 mIU per liter or higher, although long-term benefits have not been shown and the risks of such treatment are unknown. For persons older than 70 years of age or for persons who have a thyrotropin level of less than 10 mIU per liter, treatment decisions should be guided by individual patient factors, including the extent of thyrotropin elevation and whether the patient has symptoms of hypothyroidism, antibodies to thyroid peroxidase, goiter, or evidence of atherosclerotic cardiovascular disease, heart failure, or associated risk factors. If treatment is started because of symptoms of hypothyroidism, the treatment should be discontinued if no alleviation of the symptoms is observed after 3 to 6 months or if adverse effects occur. If no treatment is started, the thyrotropin level should be monitored every 6 to 12 months, and treatment should be initiated if the level increases to 10 mIU per liter or more in persons younger than 70 years of age or if other indications for treatment become apparent. Cutoff values for the levels of thyrotropin and free T4 for the diagnosis and treatment of subclinical hypothyroidism in pregnant women differ from those in nonpregnant women.