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Mitotane-Induced Endocrine Alterations in Children with Adrenocortical Carcinoma: Clinical Implications from a
Gerdi Tuli1,2, Jessica Munarin1,2, Stefano Gabriele Vallero2,3
1Department of Pediatric Endocrinology, Regina Margherita Children's Hospital, 10126 Turin, Italy.
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.
Insights
Mitotane treatment for pediatric adrenocortical carcinoma (ACC) causes significant endocrine issues, including adrenal insufficiency and precocious puberty. Close endocrine monitoring is crucial for managing these side effects in children.
Area of Science:
- Pediatric Endocrinology
- Pediatric Oncology
- Adrenocortical Carcinoma Treatment
Background:
- Mitotane is a critical treatment for adrenocortical carcinoma (ACC).
- Endocrine side effects of mitotane in pediatric patients are not well understood.
Purpose of the Study:
- To characterize the endocrine side effects of mitotane in pediatric ACC patients.
- To investigate the relationship between mitotane levels and endocrine complications.
Main Methods:
- Retrospective analysis of 11 pediatric ACC patients (2000-2025).
- Seven patients received mitotane therapy.
- Data collected: age, treatment details, serum mitotane levels, endocrine complications.
Main Results:
- All mitotane-treated patients developed adrenal insufficiency.
- Five patients experienced precocious puberty, with correlations to mitotane levels.
- Four patients developed central hypothyroidism, negatively correlated with mitotane levels.
Conclusions:
- Mitotane therapy in pediatric ACC is linked to substantial endocrine dysfunction.
- Proactive, multidisciplinary endocrine management is essential during treatment.
