eISSN: 2083-8441
ISSN: 2081-237X
Pediatric Endocrinology Diabetes and Metabolism
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vol. 30
Review paper

Precocious puberty and other endocrine disorders during mitotane treatment for paediatric adrenocortical carcinoma – case series and literature review

Elżbieta Moszczyńska
Marta Baszyńska-Wilk
Aleksandra Tutka
Agnieszka Bogusz-Wójcik
Patrycja Dasiewicz
Olga Gryniewicz-Kwiatkowska
Małgorzata Walewska-Wolf
Maria Stepaniuk
Dorota Majak
Wiesława Grajkowska

  1. Department of Endocrinology and Diabetology, The Children’s Memorial Health Institute, Warsaw, Poland
  2. Department of Oncology, The Children’s Memorial Health Institute, Warsaw, Poland
  3. Gynaecological Outpatient Clinic, The Children’s Memorial Health Institute, Warsaw, Poland
  4. Department of Pathology, The Children’s Memorial Health Institute, Warsaw, Poland
Pediatr Endocrinol Diabetes Metab 2024; 30 (1): 14-28
Online publish date: 2024/02/29
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Adrenocortical carcinoma (ACC) is rare and an aggressive tumour. Mitotane is the mainstay adjuvant drug in treating ACC. The study aimed to describe patients diagnosed with precocious puberty (PP) and other endocrinological complications during mitotane therapy.

Material and methods
This retrospective study enrolled 4 patients with ACC treated with mitotane therapy complicated by PP. We analysed clinical manifestations, radiological, histopathological findings, and hormonal results.

The median age at the diagnosis of ACC was 1.5 years. All patients were treated with surgery and mitotane, accompanied by chemotherapy regimens in 2 cases. The median time from surgery to the initiation of mitotane therapy was 26 days. During mitotane treatment, PP was confirmed based on symptoms, and hormonal and imaging tests. In one patient, incomplete peripheral PP was followed by central PP. The median time from the therapy initiation to the first manifestations of PP was 4 months. Additionally, due to mitotane-induced adrenal insufficiency, patients required a supraphysiological dose of hydrocortisone (HC), and in one patient, mineralocorticoid (MC) replacement with fludrocortisone was necessary. In 2 patients, hypothyroidism was diagnosed. All patients presented neurological symptoms of varying expression, which were more severe in younger children.

The side effects of using mitotane should be recognized quickly and adequately treated. In prepubertal children, PP could be a complication of therapy. The need to use supraphysiological doses of HC, sometimes with MC, should be highlighted. Some patients require levothyroxine replacement therapy. The neurotoxicity of mitotane is a significant clinical problem.


puberty, adrenocortical carcinoma, mitotane, virilization

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