title: Bexarotene-induced hypothyroidism: bexarotene stimulates the peripheral metabolism of thyroid hormones.
abstract: 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.
  
  
  METHODS
  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-T4 doses 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 T4 sulfate (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/rT3 ratio increased by 43%, and the T4S/FT4 ratio 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.
authors: Department of Endocrinology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. jwasmit@lumc.nl
authors: Johannes W A
authors: JW
authors: Smit
authors: Marcel P M
authors: MP
authors: Stokkel
authors: Alberto M
authors: AM
authors: Pereira
authors: Johannes A
authors: JA
authors: Romijn
authors: Theo J
authors: TJ
authors: Visser
mesh_terms: D000368:Aged; D016588:Anticarcinogenic Agents / Q000009:adverse effects*; D000077610:Bexarotene; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced* / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D047488:Retinoid X Receptors / Q000819:agonists; D013764:Tetrahydronaphthalenes / Q000009:adverse effects*; D013963:Thyroid Hormones / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000473:pathology; D013972:Thyrotropin / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013972:Thyrotropin; D000077610:Bexarotene; D013974:Thyroxine