Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism

Background Patients with hypothyroidism are usually treated with thyroxine (levothyroxine) only, although both thyroxine and triiodothyronine are secreted by the normal thyroid gland. Whether thyroid secretion of triiodothyronine is physiologically important is unknown. Methods We compared the effects of thyroxine alone with those of thyroxine plus triiodothyronine (liothyronine) in 33 patients with hypothyroidism. Each patient was studied for two five-week periods. During one period, the patient received his or her usual dose of thyroxine. During the other, the patient received a regimen in which 50 mu g of the usual dose of thyroxine was replaced by 12.5 mu g of triiodothyronine. The order in which each patient received the two treatments was randomized. Biochemical, physiologic, and psychological tests were performed at the end of each treatment period. Results The patients had tower serum free and total thyroxine concentrations and higher serum total triiodothyronine concentrations after treatment with thyroxine plus triiodothyronine than after thyroxine alone, whereas the serum thyrotropin concentrations were similar after both treatments. Among 17 scores on tests of cognitive performance and assessments of mood, 6 were better or closer to normal after treatment with thyroxine plus triiodothyronine. Similarly, among 15 visual-analogue scales used to indicate mood and physical status, the results for 10 were significantly better after treatment with thyroxine plus triiodothyronine. The pulse rate and serum sex hormone-binding globulin concentrations were slightly higher after treatment with thyroxine plus triiodothyronine, but blood pressure, serum lipid concentrations, and the results of neurophysiologic tests were similar after the two treatments. Conclusions In patients with hypothyroidism, partial substitution of triiodothyronine for thyroxine may improve mood and neuropsychological function; this finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland. (N Engl J Med 1999;340:424-9.) (C)1999. Massachusetts Medical Society.