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

J Clin Endocrinol Metab. 2011 Nov;96(11):3466-74. doi: 10.1210/jc.2011-1329. Epub 2011 Aug 24.


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.

Trial registration: NCT00106119.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Apolipoproteins B / blood
  • Body Composition / drug effects
  • Bone Density / drug effects
  • Cholesterol / blood
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Hypothyroidism / blood
  • Hypothyroidism / drug therapy*
  • Male
  • Middle Aged
  • Quality of Life
  • Thyroid Hormones / blood
  • Thyroxine / administration & dosage
  • Thyroxine / therapeutic use*
  • Treatment Outcome
  • Triiodothyronine / administration & dosage
  • Triiodothyronine / therapeutic use*


  • Apolipoproteins B
  • Thyroid Hormones
  • Triiodothyronine
  • Cholesterol
  • Thyroxine

Associated data