Metabolic effects of liothyronine therapy in hypothyroidism: A randomized, double-blind, crossover trial of liothyronine versus levothyroxine

Abstract

Context: Levothyroxine (L-T 4) therapy is based on the assumption that the conversion of T 4 into T 3provides adequate amounts of active hormone at target tissues. However, in rodents, L-T 4 alone does not restore a euthyroid state in all tissues. Previous combination L-T 4/liothyronine (L-T 3) therapy trials focused on quality-of-life endpoints, and limited information is available on the effects on other measures of thyroid hormone action. Objective: Our objective was to evaluate the efficacy of thyroid hormone replacement with L-T 4 or L-T 3 at doses producing equivalent normalization of TSH. Participants, Design, and Setting: Fourteen hypothyroid patients participated in this randomized, double-blind, crossover intervention at the National Institutes of Health Clinical Center. Interventions: L-T 3 or L-T 4 were administered thrice daily to achieve a target TSH from 0.5-1.5 mU/liter. Volunteers were studied as inpatients after 6 wk on a stable dose and at the target TSH. Main Outcome Measures: Serum thyroid hormones, lipid parameters, and indices of glucose metabolism were evaluated. Results: No difference was observed in TSH between L-T 3 and L-T 4 treatments. L-T 3 resulted in significant weight loss [L-T 4, 70.6 ± 12.5, vs. L-T 3, 68.5 ± 11.9 kg (P = 0.009)] and in a 10.9 ± 10.0% decrease in total cholesterol (P = 0.002), 13.3 ± 12.1% decrease in low-density lipoprotein-cholesterol (P = 0.002), and an 18.3 ± 28.6% decrease in apolipoprotein B (P = 0.018). No significant differences were observed in high-density lipoprotein-cholesterol, heart rate, blood pressure, exercise tolerance, or insulin sensitivity. Conclusions: The substitution of L-T 3 for L-T 4 at equivalent doses (relative to the pituitary) reduced body weight and resulted in greater thyroid hormone action on the lipid metabolism, without detected differences in cardiovascular function or insulin sensitivity. Copyright © 2011 by The Endocrine Society.