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

Francesco S Celi, Marina Zemskova, Joyce D Linderman, Sheila Smith, Bart Drinkard, Vandana Sachdev, Monica C Skarulis, Merel Kozlosky, Gyorgy Csako, Rene Costello, Frank Pucino
Journal of Clinical Endocrinology and Metabolism 2011, 96 (11): 3466-74

CONTEXT: Levothyroxine (L-T(4)) therapy is based on the assumption that the conversion of T(4) into T(3) provides 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.

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