Mitotane-Induced Endocrine Alterations in Children with Adrenocortical Carcinoma: Clinical Implications from a 20-Year Retrospective Study

Tuli, Gerdi; Munarin, Jessica; Vallero, Stefano Gabriele; Piglione, Matilde; Biasin, Eleonora; De Sanctis, Luisa; Fagioli, Franca

doi:10.3390/children12081031

Open AccessArticle

Mitotane-Induced Endocrine Alterations in Children with Adrenocortical Carcinoma: Clinical Implications from a 20-Year Retrospective Study

by

Gerdi Tuli

^1,2,*

,

Jessica Munarin

^1,2,

Stefano Gabriele Vallero

^2,3,

Matilde Piglione

^2,3,

Eleonora Biasin

^2,3,

Luisa De Sanctis

^1,2

and

Franca Fagioli

^2,3

¹

Department of Pediatric Endocrinology, Regina Margherita Children’s Hospital, 10126 Turin, Italy

²

Department of Pediatrics, University of Turin, 10124 Torino, Italy

³

Department of Pediatric Oncoematology, Regina Margherita Children’s Hospital, AOU Città della Salute e della Scienza, 10126 Turin, Italy

^*

Author to whom correspondence should be addressed.

Children 2025, 12(8), 1031; https://doi.org/10.3390/children12081031

Submission received: 27 June 2025 / Revised: 21 July 2025 / Accepted: 4 August 2025 / Published: 5 August 2025

(This article belongs to the Section Pediatric Endocrinology & Diabetes)

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Abstract

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 ± 1.45 years, with a mean follow-up of 10.05 ± 2.45 years. Patients received mitotane for an average of 2.5 ± 0.54 years, with a mean daily dose of 2805.5 ± 145.82 mg and a mean serum level of 16.1 ± 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.

Keywords: pediatric adrenocortical carcinoma; mitotane; endocrine effects

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MDPI and ACS Style

Tuli, G.; Munarin, J.; Vallero, S.G.; Piglione, M.; Biasin, E.; De Sanctis, L.; Fagioli, F. Mitotane-Induced Endocrine Alterations in Children with Adrenocortical Carcinoma: Clinical Implications from a 20-Year Retrospective Study. Children 2025, 12, 1031. https://doi.org/10.3390/children12081031

AMA Style

Tuli G, Munarin J, Vallero SG, Piglione M, Biasin E, De Sanctis L, Fagioli F. Mitotane-Induced Endocrine Alterations in Children with Adrenocortical Carcinoma: Clinical Implications from a 20-Year Retrospective Study. Children. 2025; 12(8):1031. https://doi.org/10.3390/children12081031

Chicago/Turabian Style

Tuli, Gerdi, Jessica Munarin, Stefano Gabriele Vallero, Matilde Piglione, Eleonora Biasin, Luisa De Sanctis, and Franca Fagioli. 2025. "Mitotane-Induced Endocrine Alterations in Children with Adrenocortical Carcinoma: Clinical Implications from a 20-Year Retrospective Study" Children 12, no. 8: 1031. https://doi.org/10.3390/children12081031

APA Style

Tuli, G., Munarin, J., Vallero, S. G., Piglione, M., Biasin, E., De Sanctis, L., & Fagioli, F. (2025). Mitotane-Induced Endocrine Alterations in Children with Adrenocortical Carcinoma: Clinical Implications from a 20-Year Retrospective Study. Children, 12(8), 1031. https://doi.org/10.3390/children12081031

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Mitotane-Induced Endocrine Alterations in Children with Adrenocortical Carcinoma: Clinical Implications from a 20-Year Retrospective Study

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