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Augmented Hepatic and Skeletal Thyromimetic Effects of Tiratricol in Comparison with Levothyroxine¹

Section of Endocrine Neoplasia and Hormonal Disorders, University of Texas, M. D. Anderson Cancer Center (S.I.S., M.J.S.), Houston, Texas 77030; the Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine (M.D.R., P.W.L.), Baltimore, Maryland 21287; and the Section of Cardiology, Baylor College of Medicine (H.A.K., W.A.Z.), Houston, Texas 77030

Address all correspondence and requests for reprints to: Steven I. Sherman, M.D., University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 15, Houston, Texas 77030.

Abstract

A thyroid hormone analog with organ-selective effects could have therapeutic application for disorders such as hyperlipidemia and osteoporosis. We performed a randomized clinical trial to determine the specific thyromimetic effects of tiratricol. Twenty-four athyreotic patients underwent detailed metabolic and physiological evaluation after a 2-month baseline period, taking TSH-suppressive doses of L-T₄. They were then randomized to blinded treatment with either tiratricol (24 µg/kg twice daily) or L-T₄ (1.9 µg/kg daily). The dose of hormone was increased until the TSH level was less than 0.1 mU/L, and the metabolic and physiological testing was repeated. Comparing the change from baseline to the study drug periods, when serum TSH levels were equivalently suppressed, there were no significant differences between the two groups in resting metabolic rate, weight, urea nitrogen excretion, or symptom score. Plasma total and low density lipoprotein cholesterol levels declined 13 ± 4% and 23 ± 6% in the tiratricol group compared with 2 ± 2% and 5 ± 3% in the L-T₄ group (P = 0.015 and P = 0.0066, respectively). Serum sex hormone-binding globulin levels increased 55 ± 13% with tiratricol compared with a 1.7 ± 4% decline with L-T₄ (P = 0.0006), indicating an augmented hepatic response to tiratricol. Skeletal metabolic activity was enhanced, with increased levels of serum osteocalcin and urinary excretion of calcium and pyridinium cross-links. Tiratricol and L-T₄ had comparable effects on cardiovascular function. Tiratricol has distinct augmented hepatic and skeletal thyromimetic actions of potential therapeutic value.

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