{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:23:51Z","timestamp":1791829431726,"version":"4.3.4"},"reference-count":71,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Despite the pivotal role of mitotane in adrenocortical carcinoma (ACC) management, data on the endocrine toxicities of this treatment are lacking. The aim of this systematic review is to collect the available evidence on the side effects of mitotane on the endocrine and metabolic systems in both children and adults affected by adrenal carcinoma. Sixteen articles on 493 patients were included. Among the adrenal insufficiency, which is an expected side effect of mitotane, 24.5% of patients increased glucocorticoid replacement therapy. Mineralocorticoid insufficiency usually occurred late in treatment in 36.8% of patients. Thyroid dysfunction is characterized by a decrease in FT4, which occurs within 3\u20136 months of treatment in 45.4% of patients, while TSH seems to not be a reliable marker. Dyslipidemia is characterized by an increase in both LDL-c and HDL-c (54.2%). Few studies have found evidence of hypertriglyceridemia. In males, gynecomastia and hypogonadism can occur after 3\u20136 months of treatment (38.4% and 35.6%, respectively), while in pre-menopausal women, mitotane can cause ovarian cysts and, less frequently, menstrual disorders. Most of these side effects appear to be reversible after mitotane discontinuation. We finally suggest an algorithm that could guide metabolic and endocrine safety assessments in patients treated with mitotane for ACC.<\/jats:p>","DOI":"10.3390\/cancers13195001","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T09:24:04Z","timestamp":1633598644000},"page":"5001","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Metabolic and Endocrine Toxicities of Mitotane: A Systematic Review"],"prefix":"10.3390","volume":"13","author":[{"given":"Marta","family":"Bianchini","sequence":"first","affiliation":[{"name":"Oncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Puliani","sequence":"additional","affiliation":[{"name":"Oncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy"},{"name":"Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonsina","family":"Chiefari","sequence":"additional","affiliation":[{"name":"Oncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilda","family":"Mormando","sequence":"additional","affiliation":[{"name":"Oncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Lauretta","sequence":"additional","affiliation":[{"name":"Oncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2124-1335","authenticated-orcid":false,"given":"Marialuisa","family":"Appetecchia","sequence":"additional","affiliation":[{"name":"Oncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1210\/jcem-23-9-918","article-title":"A Peripheral Action of O,P\u2032-Ddd on Steroid Biotransformation","volume":"23","author":"Bradlow","year":"1963","journal-title":"J. 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