Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study

Abstract

Objective: To compare the effects of a unique fixed combination levothyroxine/liothyronine (LT4/LT3) therapy in patients with primary hypothyroidism. Subjects and methods: This is a randomized, double-blind, crossover study. Adults with primary hypothyroidism (n = 32, age 42.6 ± 13.3, 30 females) on stable doses of LT4 for ≥ 6 months (125 or 150 μg/day) were randomized to continue LT4 treatment (G1) or to start LT4/LT3 therapy (75/15 μg/day; G2). After 8 weeks, participants switched treatments for 8 more weeks. Thyroid function, lipid profile, plasma glucose, body weight, electrocardiogram, vital signs, and quality of life (QoL) were evaluated at weeks 0, 8 and 16. Results: Free T4 levels were significantly lower while on LT4/LT3 (G1: 1.07 ± 0.29 vs. 1.65 ± 0.46; G2: 0.97 ± 0.26 vs. 1.63 ± 0.43 ng/dL; P < 0.001). TSH and T3 levels were not affected by type of therapy. More patients on LT4/ LT3 had T3 levels above the upper limit (15% vs. 3%). The combination therapy led to an increase in heart rate, with no significant changes in electrocardiogram or arterial blood pressure. Lipid profile, body weight and QoL remained unchanged. Conclusions: The combination therapy yielded significantly lower free T4 levels, with no changes in TSH or T3 levels. More patients on LT4/T3 had elevated T3 levels, with no significant alterations in the evaluated outcomes. No clear clinical benefit of the studied formulation could be observed. Future trials need to evaluate different formulations and the impact of the combined therapy in select populations with genetic polymorphisms. Arch Endocrinol Metab. 2016;60(6):562-72

MANAGEMENT OF ENDOCRINE DISEASE: Pitfalls on the replacement therapy for primary and central hypothyroidism in adults

“…Bunevicius et al described an increase in well-being, mood and psychometric functionality in patients treated with LT4/LT3 treatment (66), and two other studies also showed similar beneficial effect (67,68). Those findings could not be further replicated by other studies (69,70,71,72,73). The study with the largest sample size, 697 patients, and longest follow-up was conducted by Saravanan and coworkers.…”

Current evidence for the treatment of hypothyroidism with levothyroxine/levotriiodothyronine combination therapy versus levothyroxine monotherapy

“…Studies comparing QoL, mood and cognitive outcomes and patients' preference for treatment with LT4/LT3 combination therapy versus LT4 monotherapy are described in Table 1. 22,31,[42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] Among these 17 studies, 1 older study using very high LT4 and LT4/LT3 doses found that LT4 monotherapy had a more favourable adverse event profile and was preferred by patients versus LT4/LT3 combination therapy. 54 This study should likely be viewed from a historical perspective only because the conditions of treatment are dissimilar to the more modern studies listed below.…”

“…22,42 The results of 10 studies, however, were neutral, finding no consistent advantage for monotherapy or combination treatment. 31,[46][47][48][49][51][52][53]56,57 Thus, the comparisons of LT4/LT3 combination therapy versus LT4 monotherapy produced mixed and equivocal results. It should be noted that there were large placebo effects in two of these studies: one that found an advantage with LT4/LT3 combination treatment and one in which results did not favour either treatment.…”

“…In two studies without obvious objective differentiation, the authors nonetheless noted a subjective preference for LT4/LT3 combination therapy over LT4 monotherapy . The results of 10 studies, however, were neutral, finding no consistent advantage for monotherapy or combination treatment . Thus, the comparisons of LT4/LT3 combination therapy versus LT4 monotherapy produced mixed and equivocal results.…”

“…Studies comparing QoL, mood and cognitive outcomes and patients' preference for treatment with LT4/LT3 combination therapy versus LT4 monotherapy are described in Table . Among these 17 studies, 1 older study using very high LT4 and LT4/LT3 doses found that LT4 monotherapy had a more favourable adverse event profile and was preferred by patients versus LT4/LT3 combination therapy .…”