Bexarotene-induced central hypothyroidism misinterpreted as over supplementation of thyroid hormone

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Conference Proceeding

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Endocr Pract


Objective: Thyroid dysfunction has been identified as a side effect of several currently used anticancer medications. It is important for physicians to be familiar and up-to-date with these medications and their common endocrine side effects. This is a case of bexarotene-induced thyroid disorder. Case Presentation: 66-year-old female with mycosis fungoides (cutaneous T-cell lymphoma), treated with bexarotene since 2010, presented to the endocrine clinic for evaluation of abnormal thyroid function. One year after initiating bexarotene, she was diagnosed with hypothyroidism by a free T4 of 0.71 (0.8-1.8 ng/dl) and started on levothyroxine. She was taking levothyroxine 125 mcg daily. Her TSH levels remained detectable ranging from 0.31 to 1.26 (0.3 - 5.00 uIU/mL) until from 1 year ago when TSH became undetectable at < 0.01 uIU/ mL. Her primary care doctor interpreted the low TSH to be secondary to overreplacement of thyroid hormone. The levothyroxine dose was therefore lowered to 100 mcg and then 75 mcg, yet TSH remained suppressed and free T4 declined, prompting referral to endocrinology. Labs on initial presentation to our clinic were significant for TSH < 0.01 (0.45 - 5.33 uIU/mL) and free T4 of 0.59 (0.61 - 1.44 ng/dL). Thyroid ultrasound confirmed a normal homogeneous thyroid gland without nodules and without increased vascularity. We recognized her hypothyroidism was central in origin due to bexarotene and increased her dose to 100 mcg once daily with improvement of free T4 into the normal range. Conclusion: Bexarotene was approved in 1999 by the US Food and Drug Administration as a second-line treatment for early- and late-stage refractory cutaneous T-cell lymphomas. The molecule is highly selective for the retinoid X receptor (RXR). Reversible, dose-dependent, RXR-mediated thyroid hormone-independent suppression of TSH gene expression is well described with this drug. Suppression of TSH can occur instantly even after the first dose of the medication. A second mechanism of hypothyroidism is increased peripheral degradation of thyroid hormones. Treatment of patients with bexaroteneinduced hypothyroidism frequently requires higher doses of thyroid hormone, often twice the typical doses used to treat more common etiologies of hypothyroidism. Since bexarotene results in TSH suppression, TSH levels are an unreliable measure of thyroid function. Measurement of free T4 and T3 should be monitored to determine adequacy of supplementation. Increased awareness of this drug-induced endocrine side effect is important to avoid incorrect interpretation of a low TSH.



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