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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

Department of Endocrinology and Diabetes (J.P.W., L.C.W., B.G.A.S., S.S.D., G.T.C., M.C.B., A.J.C.) and Psychiatry and Behavioural Science (L.S.), Sir Charles Gairdner Hospital; and Western Australian Center for Pathology and Medical Research (PathCentre) (E.M.L., C.I.B.), Nedlands, Western Australia 6009, Australia

Address all correspondence and requests for reprints to: Dr. John P. Walsh, Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia. E-mail: john.walsh{at}health.wa.gov.au.

T₄ is standard treatment for hypothyroidism. A recent study reported that combined T₄/liothyronine (T₃) treatment improved well-being and cognitive function compared with T₄ 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 µg was substituted for 50 µg of the patients’ usual T₄ dose. No significant (P < 0.05) difference between T₄ and combined T₄/T₃ 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 Questionnaire-28 and visual analog scales assessing anxiety and nausea, scores were significantly (P < 0.05) worse for combined treatment than for T₄ alone. Serum TSH was lower during T₄ treatment than during combined T₄/T₃ 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 T₄ alone. We conclude that in the doses used in this study, combined T₄/T₃ treatment does not improve well-being, cognitive function, or quality of life compared with T₄ alone.

This work was supported by Sir Charles Gairdner Hospital Research Foundation.

Abbreviations: GHQ-28, General Health Questionnaire 28; SF-36, Short Form 36; TSQ, Thyroid Symptom Questionnaire.

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