Objective: Therapy with the retinoid X receptor agonist bexarotene is associated with hypothyroidism caused by decreased pituitary TSH secretion. To evaluate the effects of bexarotene on peripheral thyroid hormone metabolism, we performed a study in athyreotic subjects on a fixed substitution dose with L-T4. Design: The design was an open prospective 6-wk intervention study. Methods: Ten athyreotic patients with pulmonary metastases of differentiated thyroid carcinoma received 6-wk redifferentiation treatment with 300 mg bexarotene/d. L-T4doses were kept stable. Before and in the sixth week of therapy, serum levels of total T4, free T4(FT4), T3, reverse T3(rT3), and TSH were measured. To study nondeiodinase-mediated thyroid hormone degradation, serum levels of T4sulfate (T4S) were measured. Recombinant human TSH was administered before and in the sixth week of bexarotene therapy. Results: Bexarotene induced profound decreases in total T4(56% of baseline), FT4(47%), T3(69%), rT3(51%), and T4S (70%) in all patients, whereas TSH levels were not affected. The T3/rT3ratio increased by 43%, and the T4S/FT4ratio increased by 48%. Serum TSH levels before and after recombinant human TSH were unaffected by bexarotene. Conclusions: In the present study, we demonstrate that increased peripheral degradation of thyroid hormones by a nondeiodinase-mediated pathway contributes to bexarotene induced-hypothyroidism. Copyright

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Persistent URL dx.doi.org/10.1210/jc.2006-2822, hdl.handle.net/1765/35350
Smit, J.W.A, Stokkel, M, Pereira, A.M, Romijn, J.A, & Visser, T.J. (2007). Bexarotene-induced hypothyroidism: Bexarotene stimulates the peripheral metabolism of thyroid hormones. Journal of Clinical Endocrinology and Metabolism, 92(7), 2496–2499. doi:10.1210/jc.2006-2822