Review: available evidence does not support a benefit for thyroid hormone replacement in adults with subclinical hypothyroidism.

M e t h o d s Data sources: MEDLINE, EMBASE/ Excerpta Medica, CINAHL, and LILACS to May 2006; Cochrane Library (2006, Issue 1); Current Controlled Trials; references of relevant studies and systematic reviews; experts; and pharmaceutical companies. Study selection and assessment: Randomized controlled trials (RCTs) that compared thyroid hormone replacement therapy (triiodothyronine [T3], thyroxine [T4], or both) with placebo or no treatment in adult outpatients with subclinical hypothyroidism and no severe illness. Treatment was given for ≥ 1 month with ≥ 3 months of follow-up. Subclinical hypothyroidism was defined as a thyroid-stimulating hormone (TSH) level greater than the upper limit of the test reference value. 12 RCTs (n = 485, > 75% women) met the selection criteria; all compared levothyroxine replacement (LT4) with placebo (11 RCTs) or no treatment (1 RCT). Daily LT4 doses varied from 65 μg (4 trials) to 150 μg (1 trial), and study duration was 6 to 14 months. All trials were of moderate or good quality (Jadad scale ≥ 3). Outcomes: Cardiovascular mortality or morbidity, hypothyroidism signs and symptoms, and health-related quality of life. Secondary outcomes included all-cause mortality and adverse effects.