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

Author(s): Golden WM, Weber KB, Hernandez TL, Sherman SI, Woodmansee WW, Haugen BR

Affiliation(s): Division of Endocrinology, Metabolism, and Diabetes, University of Colorado at Denver & Health Sciences Center, Aurora, CO; University of Texas, M.D. Anderson Cancer Center, Houston TX; University of Colorado Cancer Center, Aurora, CO.

Publication date & source: 2006-10-24, J Clin Endocrinol Metab., [Epub ahead of print]

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 are not clear. Objective: To determine the effect of a single dose of bexarotene on levels of TSH, T4 and T3 in healthy subjects. Design: Randomized, double-blind, placebo-controlled, cross-over trial. Setting: General Clinical Research Center. Subjects: Six healthy adults (> 18 yr old). Intervention: Single dose rexinoid (bexarotene, 400 mg/m(2)) or placebo, with TSH measurements at 0, 1, 2, 4, 8, 12, 24 and 48 h. Main Outcome Measure: Serum TSH 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 = 0.04); the nadir of 0.32 +/- 0.02 mU/L (P < 0.001) was seen at 24 h. Serum total T4, free T4, reverse T3, prolactin, cortisol, and triglycerides were not affected (P > 0.05 for all). Serum T3 levels were lower in the bexarotene arm compared with placebo (P = 0.001), and the effect was significant at 4, 12, 24 and 48 h (P < 0.05 for all). 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.

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