Mitotane in the treatment of childhood adrenocortical carcinoma: a potent endocrine disruptor

Endocrinology, Diabetes & Metabolism Case Reports
Philip D OddiePhilippa J Carter

Abstract

Adrenocortical carcinoma (ACC) during childhood is a rare malignant tumor that frequently results in glucocorticoid and/or androgen excess. When there are signs of microscopic or macroscopic residual disease, adjuvant therapy is recommended with mitotane, an adrenolytic and cytotoxic drug. In addition to the anticipated side effect of adrenal insufficiency, mitotane is known to cause gynecomastia and hypothyroidism in adults. It has never been reported to cause precocious puberty. A 4-year-old girl presented with a 6-week history of virilization and elevated androgen levels and 1-year advancement in bone age. Imaging revealed a right adrenal mass, which was subsequently surgically excised. Histology revealed ACC with multiple unfavorable features, including high mitotic index, capsular invasion and atypical mitoses. Adjuvant chemotherapy was started with mitotane, cisplatin, etoposide and doxorubicin. She experienced severe gastrointestinal side effects and symptomatic adrenal insufficiency, which occurred despite physiological-dose corticosteroid replacement. She also developed hypothyroidism that responded to treatment with levothyroxine and peripheral precocious puberty (PPP) with progressive breast development and rapidly a...Continue Reading

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Citations

Jan 24, 2020·Pediatric Hematology and Oncology·Wael ZekriAhmad S Alfaar
Jan 9, 2021·Frontiers in Endocrinology·Salvatore Benvenga
Apr 28, 2021·In Vitro Cellular & Developmental Biology. Animal·Luis Daniel Goyzueta MamaniCarlos Ricardo Soccol
Jul 22, 2021·European Journal of Drug Metabolism and Pharmacokinetics·Malik Salman HaiderRobert Luxenhofer

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