**3.5. Bexarotene**

Bexarotene is a selective agonist of the retinoid X receptor (RXR), a nuclear hormone receptor. It is approved for the treatment of cutaneous T cell lymphoma and has been found to induce secondary hypothyroidism [102]. Bexarotene appears to interfere with the normal feedback of thyroid hormone on the pituitary gland [102,149]. T3 binding to its receptor in the pituitary leads to heterodimerization of the receptor with RXR, which suppresses transcription of the β-subunit of TSH, which is required for thyroid stimulation. Bexarotene also has TSH-independent effects on thyroid hormone metabolism. Thyroidectomized thyroid cancer patients receiving thyroid hormone replacement who started bexarotene had a dramatic decrease in total T3 and T4, and free T4 levels with TSH levels that failed to rise appropriately [150].This may be probably due to an effect on peripheral thyroid hormone metabolism via non-deiodinase mechanisms.
