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

Abstract

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: ClinicalTrials.gov NCT02317926.

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

Figure 1.

Flow diagram: enrollment, allocation, and completion of the study. Numbers of patients in each arm indicated in parentheses. DTE, desiccated thyroid extract; LT3- liothyronine; LT4, levothyroxine.

Figure 2.

Boxplots showing change scores from LT4 to the LT4/LT3 combination treatment, segmented by either low, medium, or high scores for those measures while on LT4. P value reports the results of a pairwise Dunn test for each set of comparisons. Multiple comparisons are adjusted using the Holm method.

Figure 3.

Boxplots showing change scores from LT4 to the DTE treatment, segmented by either low, medium, or high scores for those measures while on LT4. P value reports the results of a pairwise Dunn test for each set of comparisons. Multiple comparisons are adjusted using the Holm method.

Figure 4.

A visualization of the pairwise correlation matrix between the various dependent measures, collected during treatment A. Positive correlations are displayed in blue with negative correlations displayed in red; the size of the circle and the intensity of the color denotes correlation strength. The diagonal is marked with a straight line of solid blue circles.

Figure 5.

Boxplots showing change scores from LT4 to the DTE treatment, segmented by either low, medium, or high scores for those measures while on LT4. P value reports the results of a pairwise Dunn test for each set of comparisons. Multiple comparisons are adjusted using the Holm method.