{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T13:36:38Z","timestamp":1781357798928,"version":"3.54.1"},"reference-count":19,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Mitotane is a key component in the treatment of adrenocortical carcinoma (ACC), but its endocrine side effects in children remain under-characterized. Methods: We conducted a retrospective analysis of 11 pediatric patients (6 males, 5 females) diagnosed with ACC and followed between 2000 and 2025. Seven received mitotane therapy. Data included age at diagnosis, treatment duration and dosage, serum mitotane levels, and endocrine complications. Results: The mean age at diagnosis was 6.6 \u00b1 1.45 years, with a mean follow-up of 10.05 \u00b1 2.45 years. Patients received mitotane for an average of 2.5 \u00b1 0.54 years, with a mean daily dose of 2805.5 \u00b1 145.82 mg and a mean serum level of 16.1 \u00b1 5.92 mg\/mL. All mitotane-treated patients developed adrenal insufficiency, requiring supraphysiological hydrocortisone replacement. Four also required mineralocorticoid therapy. Five developed precocious puberty; two males presented with prepubertal gynecomastia; three females were managed with GnRH analogs or aromatase inhibitors followed by estrogen receptor antagonists. Four patients developed central hypothyroidism, treated with levothyroxine. A positive correlation was found between mean serum mitotane levels and the onset of precocious puberty (p = 0.04), while mitotane levels correlated negatively with the development of central hypothyroidism (p = 0.001). Conclusions: Mitotane therapy in pediatric ACC is strongly associated with significant endocrine dysfunction. These findings emphasize the need for proactive, multidisciplinary endocrine management throughout treatment.<\/jats:p>","DOI":"10.3390\/children12081031","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T10:50:21Z","timestamp":1754391021000},"page":"1031","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mitotane-Induced Endocrine Alterations in Children with Adrenocortical Carcinoma: Clinical Implications from a 20-Year Retrospective Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5862-8958","authenticated-orcid":false,"given":"Gerdi","family":"Tuli","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology, Regina Margherita Children\u2019s Hospital, 10126 Turin, Italy"},{"name":"Department of Pediatrics, University of Turin, 10124 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Munarin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Regina Margherita Children\u2019s Hospital, 10126 Turin, Italy"},{"name":"Department of Pediatrics, University of Turin, 10124 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano Gabriele","family":"Vallero","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Turin, 10124 Torino, Italy"},{"name":"Department of Pediatric Oncoematology, Regina Margherita Children\u2019s Hospital, AOU Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Piglione","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Turin, 10124 Torino, Italy"},{"name":"Department of Pediatric Oncoematology, Regina Margherita Children\u2019s Hospital, AOU Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Biasin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Turin, 10124 Torino, Italy"},{"name":"Department of Pediatric Oncoematology, Regina Margherita Children\u2019s Hospital, AOU Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2113-6196","authenticated-orcid":false,"given":"Luisa","family":"De Sanctis","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Regina Margherita Children\u2019s Hospital, 10126 Turin, Italy"},{"name":"Department of Pediatrics, University of Turin, 10124 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9257-900X","authenticated-orcid":false,"given":"Franca","family":"Fagioli","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Turin, 10124 Torino, Italy"},{"name":"Department of Pediatric Oncoematology, Regina Margherita Children\u2019s Hospital, AOU Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.5114\/pedm.2024.139271","article-title":"Adrenal cortical carcinoma: Paediatric aspects\u2014Literature review","volume":"30","author":"Dasiewicz","year":"2024","journal-title":"Pediatr. 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