ENDOCRINE SIDE-EFFECTS OF ANTI-CANCER DRUGS: The impact of retinoids on the thyroid axis

Abstract

Bexarotene (Targretin), approved since 1999 as a second-line treatment for late stage cutaneous T-cell lymphomas, has been shown to induce significant hypothyroidism through TSH suppression. This review revisits, through a case report, mechanisms by which rexinoids repress the expression of TSHB gene as well as aTSH and TRH genes. It appears that rexinoids suppress TSH independently from tri-iodothyronine. Bexarotene also differently affects the gene expression of deiodinases 1 and 2 as well as the peripheral clearance of thyroxine. These data might open new ways of research on the potential interaction between thyroid axis and endogenous rexinoids.

Chemotherapy: oral side effects and dental interventions. A review of the literature

“…The chronic form is characterized by sensory paresthesias, dysesthesias, and ataxia of the extremities. Furthermore, endocrine disorders (hypothyroidism), [19] liver disease, and cutaneous disordersclosely related to targeted chemotherapy (rash, xerosis, paronychia) [20] have been related to chemotherapy.…”

The Role of Systemic Retinoids in the Treatment of Cutaneous T-Cell Lymphoma

“…In the body, retinol is metabolized to all-trans retinoic acid and then further isomerizes to 13-cis retinoic acid (isotretinoin) and 9-cis retinoic acid in the liver. 2 Subsequently, synthetic retinoids have been derived from retinol, including mono-aromatic second-generation retinoids (eg, etretinate, acitretin) followed by polyaromatic third-generation compounds called arotenoids (eg, bexarotene). 13 More recently, alitretinoin, which is a synthetic analog of 9-cis retinoic acid, has been developed with efficacy in atopic dermatitis and a few reports showing effects in MF/SS.…”

“…In contrast, isotretinoin and acitretin, RAR agonists, do not have effects on TSH levels and hypothyroidism. 2 Alitretinoin affects both RAR and RXR receptors, so it also may have effects on the thyroid hormone axis. Similar to retinoid-induced hyperlipidemia, bexarotene-induced hypothyroidism also appears to be dose dependent and reversible.…”

“…67 Because bexarotene patients typically require doses higher than replacement thyroid doses used in hypothyroidism from other causes, it has been suggested that an increase in metabolism of thyroid hormone also may play a role, perhaps through induction of liver metabolic oxidative enzymes by retinoids. 2,68 Patients should be started on empiric thyroid supplementation at onset of treatment with bexarotene (25-50 mg daily) and increased based on monthly serum-free thyroxine (free T4) levels. TSH remains suppressed while on bexarotene, even with adequate levothyroxine supplementation so the TSH should not be used as the basis by which one adjusts levothyroxine dose.…”

“…Retinoid receptors are found ubiquitously in virtually all organ systems, and they regulate important functions in the body, including embryonic development, vision, immune and neural function, as well as cell proliferation, differentiation, and apoptosis. 1,2 These compounds exert their effects through control of gene expression. In the treatment of cancer, the retinoids are considered "biologic response modifiers" (BRMs) in that they are dissimilar to traditional cytotoxic chemotherapy, inducing response without immune suppression, and often augmenting the immune response.…”