Combined Thyroxine/Liothyronine Treatment Does Not Improve Well-Being, Quality of Life, or Cognitive Function Compared to Thyroxine Alone: A Randomized Controlled Trial in Patients with Primary Hypothyroidism
Journal of Clinical Endocrinology and Metabolism
T 4 is standard treatment for hypothyroidism. A recent study reported that combined T 4 /liothyronine (T 3 ) treatment improved well-being and cognitive function compared with T 4 alone. We conducted a double-blind, randomized, controlled trial with a crossover design in 110 patients (101 completers) with primary hypothyroidism in which liothyronine 10 g was substituted for 50 g of the patients' usual T 4 dose. No significant (P < 0.05) difference between T 4 and combined T 4 /T 3 treatment was
... /T 3 treatment was demonstrated on cognitive function, quality of life scores, Thyroid Symptom Questionnaire scores, subjective satisfaction with treatment, or eight of 10 visual analog scales assessing symptoms. For the General Health Question-naire-28 and visual analog scales assessing anxiety and nausea, scores were significantly (P < 0.05) worse for combined treatment than for T 4 alone. Serum TSH was lower during T 4 treatment than during combined T 4 /T 3 treatment (mean ؎ SEM, 1.5 ؎ 0.2 vs. 3.1 ؎ 0.2 mU/liter; P < 0.001), a potentially confounding factor; however, subgroup analysis of subjects with comparable serum TSH concentrations during each treatment showed no benefit from combined treatment compared with T 4 alone. We conclude that in the doses used in this study, combined T 4 /T 3 treatment does not improve well-being, cognitive function, or quality of life compared with T 4 alone. (J Clin Endocrinol Metab 88: 4543-4550, 2003) Patients and Methods Patients and recruitment Recruitment to the study commenced in April 2000, and the study was completed in November 2002. We aimed to enroll both subjects with persistent symptoms despite T 4 therapy and also subjects who felt well while taking T 4 , but specific recruitment targets were not set for these subgroups. Inclusion criteria were primary hypothyroidism of at least 6-month duration, a stable dose of T 4 of 100 g/d or more, no change in T 4 dosage in the previous 2 months, and serum TSH concentration between 0.1-4.0 mU/liter (reference range in our laboratory, 0.3-4.0 mU/liter) at a screening visit. The diagnosis of hypothyroidism was confirmed from medical or laboratory records or by contacting primary Abbreviations: GHQ-28, General Health Questionnaire 28; SF-36, Short Form 36; TSQ, Thyroid Symptom Questionnaire.