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Single-Dose Rexinoid Rapidly and Specifically Suppresses Serum Thyrotropin in Normal Subjects

Division of Endocrinology, Metabolism, and Diabetes (W.M.G., K.B.W., T.L.H., W.W.W., B.R.H.), University of Colorado at Denver and Health Sciences Center, Aurora, Colorado 80045; University of Texas, M.D. Anderson Cancer Center (S.I.S.), Houston, Texas 77230-1402; and University of Colorado Cancer Center (B.R.H.), Aurora, Colorado 80045

Address all correspondence and requests for reprints to: Bryan R. Haugen, M.D., Associate Professor of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado at Denver and Health Sciences Center, Building RC-1 South Tower, MS 8106; 12801 East 17th Avenue, P.O. Box 6511, Aurora, Colorado 80045. E-mail: bryan.haugen{at}uchsc.edu.

Context: Retinoid X receptor agonists (rexinoids) have demonstrated benefit in patients with certain malignancies but appear to cause central hypothyroidism in some patients with advanced cancer. The influence of rexinoids on thyroid function in healthy subjects is not clear.

Objective: The objective of this study was to determine the effect of a single dose of bexarotene on levels of TSH, T₄, and T₃ in healthy subjects.

Design: This study was a randomized, double-blind, placebo-controlled, crossover trial.

Setting: This study was conducted at the General Clinical Research Center (University of Colorado Health Sciences Center, Aurora, CO).

Subjects: Six healthy adults (>18 yr old) were studied.

Intervention: Single-dose rexinoid (bexarotene, 400 mg/m²) or placebo, with TSH measurements at 0, 1, 2, 4, 8, 12, 24, and 48 h, were used.

Main Outcome Measure: The main outcome was the serum TSH level at 24 h.

Results: Single-dose bexarotene suppressed serum TSH (P < 0.001) over time. Compared with placebo, levels of TSH were significantly lower by 12 h (P = 0.043); the nadir of 0.32 ± 0.02 mU/liter (P < 0.001) was seen at 24 h. Free T₄ index and free T₃ index were also significantly lower than placebo over time (48 h) (P = 0.029; P = 0.004, respectively). Serum prolactin, cortisol, and triglycerides were not affected (P > 0.05 for all). There was no significant effect of single-dose bexarotene on rT₃ or T₃/rT₃ ratio at 24 h.

Conclusion: A single dose of a rexinoid can rapidly and specifically suppress serum TSH levels in healthy subjects. These data provide insight into the mechanisms by which rexinoids cause central hypothyroidism and potential ways this effect can be used for treatment of disorders such as thyroid hormone resistance and TSH-secreting pituitary tumors.

This article has been cited by other articles:

				J. W. A. Smit, M. P. M. Stokkel, A. M. Pereira, J. A. Romijn, and T. J. Visser Bexarotene-Induced Hypothyroidism: Bexarotene Stimulates the Peripheral Metabolism of Thyroid Hormones J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2496 - 2499. [Abstract] [Full Text] [PDF]