title: 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.
  
  
  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.
authors.affiliation: Serviço de Endocrinologia e Metabologia (SEMPR), Departamento de Medicina Interna, Hospital das Clínicas da Universidade Federal do Paraná (HC-UFPR), Curitiba, PR, Brasil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Kaminski
authors.affiliation: Serviço de Endocrinologia e Metabologia (SEMPR), Departamento de Medicina Interna, Hospital das Clínicas da Universidade Federal do Paraná (HC-UFPR), Curitiba, PR, Brasil.
authors.forename: Fabíola Yukiko
authors.initials: FY
authors.lastname: Miasaki
authors.affiliation: Genome Sciences Department, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Paz-Filho
authors.affiliation: Serviço de Endocrinologia e Metabologia (SEMPR), Departamento de Medicina Interna, Hospital das Clínicas da Universidade Federal do Paraná (HC-UFPR), Curitiba, PR, Brasil.
authors.forename: Hans
authors.initials: H
authors.lastname: Graf
authors.affiliation: Serviço de Endocrinologia e Metabologia (SEMPR), Departamento de Medicina Interna, Hospital das Clínicas da Universidade Federal do Paraná (HC-UFPR), Curitiba, PR, Brasil.
authors.forename: Gisah Amaral de
authors.initials: GA
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D013960:Thyroid Function Tests; D013972:Thyrotropin / Q000187:drug effects; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D014284:Triiodothyronine; D013972:Thyrotropin; D002784:Cholesterol; D013974:Thyroxine