Effect of thyroid hormone replacement on methionine-stimulated homocysteine levels in patients with subclinical hypothyroidism: A randomized, double-blind, placebo-controlled study

Objective: To determine whether treatment of subclinical hypothyroidism with levothyroxine would improve homocysteine metabolism. Methods: Twenty-four patients with subclinical hypothyroidism who had thyrotropin (thyroid-stimulating hormone or TSH) levels between 5 and 10 μIU/mL and normal free thyroxine concentrations were recruited from a primary care clinic and were randomized to receive levothyroxine (N = 12) or placebo (N = 12) for a period of 6 months in a double-blind, placebo-controlled study. Homocysteine was measured during fasting and after methionine challenge at the beginning and the end of the study in all patients treated with levothyroxine or placebo. Results: The 12 patients treated with levothyroxine had normal TSH levels at the end of the study, with a median value of 1.8 μIU/mL. The 12 patients receiving placebo had a median TSH of 6.0 μIU/mL after the 6-month study period. The ratio of fasting homocysteine at 6 months in comparison with baseline was 1.16 (95% confidence interval, 0.90 to 1.63) for the levothyroxine-treated group and 1.00 (0.88 to 1.29) for the placebo group (P = 0.95). The ratio of post-methionine homocysteine at 6 months in comparison with baseline was 1.00 (95% confidence interval, 0.92 to 1.35) for the levothyroxine-treated group and 0.89 (0.68 to 1.05) for the placebo group (P = 0.081). Conclusion: In this study, levothyroxine treatment of patients with subclinical hypothyroidism did not alter homocysteine levels in the fasting or post-methionine states.