Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism

J Clin Endocrinol Metab. 2021 Oct 21;106(11):e4400-e4413. doi: 10.1210/clinem/dgab478.


Introduction: Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated thyroid extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypothyroid patients, while also exploring the most symptomatic patients.

Methodology: Prospective, randomized, double-blind, crossover study of 75 hypothyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores on the 36-point thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). Secondary endpoints included treatment preference, biochemical and metabolic parameters, etiology of hypothyroidism, and Thr92Ala-DIO2 gene polymorphism. Analyses were performed with a linear mixed model using subject as a random factor and group as a fixed effect.

Results: Serum TSH remained within reference range across all treatment arms. There were no differences for primary and secondary outcomes, except for a minor increase in heart rate caused by DTE. Treatment preference was not different and there were no interferences of the etiology of hypothyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes. Subgroup analyses of the 1/3 most symptomatic patients on LT4 revealed strong preference for treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component).

Conclusions: As a group, outcomes were similar among hypothyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE.

Trial registration: NCT02317926.

Keywords: desiccated thyroid extract; hypothyroidism; levothyroxine; liothyronine; quality of life.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Cross-Over Studies
  • Desiccation
  • Double-Blind Method
  • Female
  • Hormone Replacement Therapy / methods
  • Humans
  • Hypothyroidism / drug therapy*
  • Hypothyroidism / physiopathology
  • Male
  • Middle Aged
  • Placebos
  • Prospective Studies
  • Quality of Life
  • Surveys and Questionnaires
  • Thyroid Gland / chemistry*
  • Thyroxine / administration & dosage*
  • Tissue Extracts / administration & dosage*
  • Treatment Outcome
  • Triiodothyronine / administration & dosage*
  • Triiodothyronine / blood


  • Placebos
  • Tissue Extracts
  • Triiodothyronine
  • Thyroxine

Associated data