Subclinical Hypothyroidism
Subclinical hypothyroidism is defined as an elevated serum thyrotropin (TSH) level in combination with a normal serum free T4 level. Subclinical hypothyroidism affects up to 10% of adults. Subclinical hypothyroidism may be categorized as grade 1 when TSH levels are between the upper limit of the reference range and 9.9 mU/L and as grade 2 if TSH levels are 10 mU/L or higher. Approximately 90% of patients with subclinical hypothyroidism have serum TSH levels less than 10 mU/L.
In 60% of patients with grade 1 subclinical hypothyroidism, TSH reverts to normal within 5 years. The risk of progression to overt hypothyroidism is approximately 2 to 4% per year. Grade 2 subclinical hypothyroidism is associated with increased rates of progression to overt hypothyroidism, especially in women and in patients with positive TPO antibodies. Forty percentof patients with TSH levels between 10 and 14.9 mU/L and 85% with levels between 15 and 19.9 mU/L developed overt hypothyroidism during a mean follow-up period of 32 months.
Grade 1 subclinical hypothyroidism is rarely associated with symptoms of hypothyroidism. Patients with grade 2 may have mild impairment of memory and mood.
Risk of progression is higher among women than men and among persons with higher thyrotropin levels, those with higher levels of thyroid peroxidase antibodies, and those with low-normal free T4 levels.
Grade 2 subclinical hypothyroidism is associated with increased risks of dyslipidemia, congestive heart failure, coronary artery disease events, death from coronary artery disease and cognitive decline. It remains unclear whether the use of levothyroxine treatment decreases these risks.
Because multiple factors, such as subacute thyroiditis, recovery from a nonthyroidal illness, and medications (e.g., amiodarone and lithium) can transiently increase TSH level, TSH level should be repeated before diagnosing subclinical hypothyroidism. TSH, free T4, and thyroid peroxidase antibodies should be repeated after a 2-to-3-month interval.
Levothyroxine treatment is unlikely to reduce symptoms in persons with modest elevations in TSH and minimal symptoms. Treatment is generally recommended for persons 70 years of age or younger who have thyrotropin levels of 10 mU per liter or higher.
TSH levels normally rise up to 8 mU per liter with age in individuals without thyroid disease. Older individuals who have mildly elevated TSH in the absence of thyroid disease are not at risk of increased morbidity and mortality. Treatment of persons older than 70 years of age should be based on the presence of symptoms, the extent of TSH elevation, antibodies to thyroid peroxidase, or evidence of goiter, atherosclerotic cardiovascular disease, or heart failure.
If treatment is started because of symptoms of hypothyroidism, it should be discontinued if symptoms are not alleviated within 3 to 6 months. If no treatment is started, TSH should be monitored every 6 to 12 months and treatment should be initiated if TSH increases to 10 mU per liter or more in persons younger than 70 years of age.
References
Biondi B, Cappola AR and Cooper DS. Subclinical hypothyroidism: A Review. JAMA 2019;322:153-60.
Peeters RP. Subclinical Hypothyroidism. New Engl J Med 2017;376:2556-65.
