Two small RCTs evaluated treatment of SCH with depressive symptoms and cognitive function, neither finding benefit compared with placebo.12,23 A 2018systematic review and meta-analysis of 21 studies and 2192 adults did not show a benefit to quality of life or thyroid-specific symptoms in those treated for SCH compared with controls.24
RCT support also is lacking for a reduction in cardiovascular mortality following treatment for SCH. A large population-level retrospective cohort from Denmark showed no difference in cardiovascular mortality or myocardial infarction in those treated for SCH compared with controls.25 Pooled results from 2 RCTs (for patients older than 65 years, and those older than 80 years) showed no change in risk for cardiovascular outcomes in older adults treated for SCH.26 Older adults treated for SCH in the TRUST trial showed no improvements in systolic or diastolic function on echocardiography.27 Two trials showed no difference in carotid intima-media thickness with treatment of SCH compared with placebo.28,29
While most of the RCT data come from older adults, a retrospective cohort study in the United Kingdom of younger (ages 40-70 years; n = 3093) and older (age > 70 years; n = 1642) patientsshowed a reduction in cardiovascular mortality among treated patients who were younger (hazard ratio [HR] = 0.61; 4.2% vs. 6.6%) but not those who were older (HR = 0.99; 12.7% vs. 10.7%).30 There is also evidence that thyroid size in those with goiter can be reduced with treatment of SCH.31
A measured approach to treating subclinical hypothyroidism
Consider several factors when deciding whether to treat SCH. For instance, RCT data suggest a lack of treatment benefit in relieving depression, improving cognition, or reducing general hypothyroid symptoms. Treatment of SCH in older adults does not appear to improve cardiovascular outcomes. The question of whether long-term treatment of SCH in younger patients reduces cardiovascular morbidity or mortality lacks answers from RCTs. Before diagnosing SCH or starting treatment, always confirm SCH with repeat testing in 2 to 3 months, as a high percentage of those with untreated SCH will have normal thyroid function on repeat testing.
Before diagnosing subclinical hypothyroidism (SCH) or starting treatment, always confirm SCH with repeat testing in 2 to 3 months.
In the event you and your patient elect to treat SCH, guidelines and trials generally support a low initial daily dose of 25 to 50 mcg of levothyroxine (T4), followed with dose changes every 4 to 8 weeks and a goal of normalizing TSH to within the lower half of the reference range (0.4-2.5 mIU/L).14 This is generally similar to published treatment goals for primary hypothyroidism and is based on studies suggesting the lower half of the reference range is normal for young, healthy, euthyroid individuals.32 Though full replacement doses (1.6-1.8 mcg/kg of ideal body weight) can be started for those who are elderly or who have ischemic heart disease or angina, this approach should be avoided in favor of low-dose initial therapy.33 Thyroid supplements are best absorbed when taken apart from food, calcium, or iron supplements. The ATA suggests taking thyroid medication 60 minutes before breakfast or at bedtime (3 or more hours after the evening meal).33