Endocrine Abstracts

Introduction: Central hypothyroidism is rare, estimated to occur in 1:20,000 to 1:80,000 in the general population. Pituitary mass lesions and adverse effects of their treatment are the most common causes of central hypothyroidism. In recent years, the incidence of pituitary hormonal deficiencies as adverse effects of novel molecular targeting anticancer drugs has risen sharply. Especially checkpoint inhibitors are associated with partial or complete hypopituitarism. In this report, we describe a case of isolated central hypothyroidism as a side effect of the retinoid X-receptor-selective ligand (RXR) bexarotene, used for treatment of cutaneous T-cell lymphoma.

Case report: A 74-year-oldmale patient presented with skin changes accompanied by severe pruritus. A skin biopsy revealed a cutaneous T-cell lymphoma (Sézary syndrome). Due to progressive disease under the initial therapeutic approaches, a third-line therapy with bexarotene was initiated. Only six days after initiation of bexarotene, the levels of free thyroxine (fT4) decreased to 7.7 pmol/l (with a nadir of 6.5 pmol/l in the follow-up) and the level of thyroid-stimulating hormone fell to 0.104 mIU/l (with a nadir of 0.005 mIU/l in the follow-up). Upon initiation of levothyroxine substitution (initially 50 mg/d, later 75 mg/d), the levels of fT4 increased, but remained in the hypothyroid range. After increasing the dose to 100 mg levothyroxine/day, the fT4 normalized (12.3 pmol/l). The patient did not develop symptoms of hypothyroidism and there were no deficiencies of other pituitary hormones.

Discussion: Bexarotene is a ligand of the retinoid X-receptor, and central hypothyroidism belongs to its described adverse effects. Link between thyroid function and vitamin A metabolism has been first described in the early 1970s when central hyperthyroidism was found in rats with vitamin A deficiency. Supplementation with levothyroxine reversed this by suppressing TSH secretion. Bexaroten seems to exert its effect by forming a heterodimer with thyroid hormone receptor in peripheral tissue. In addition,it inhibits the transcription of TSH-β subunit independently of triiodothyronine and promotes the clearance of thyroid hormones, resulting in accelerated hypothyroidism. Therefore, an increased thyroid replacement dose may be warranted in patients with bexarotene-induced hypothyroidism