Endocrine Abstracts

JOINT2183

Introduction: Adrenocortical carcinoma (ACC) is an extremely rare and aggressive malignancy in children, with an incidence of 0. 1–0. 3 cases per million. Pediatric ACC is often linked to germline TP53 mutations, particularly in Li-Fraumeni syndrome (LFS). We present a case of a 9-year-old girl with ACC, highlighting its aggressive course, treatment challenges, and the role of genetic predisposition.

Case Presentation: A previously healthy 9-year-old girl developed progressive weight gain, facial acne, hirsutism, and fatigue over several months. While on vacation, she experienced seizures, altered consciousness, and hypertension (150/90 mmHg), requiring emergency intubation. Imaging revealed a 10 cm right adrenal mass, and laboratory tests showed significantly elevated cortisol (1626 nmol/l; normal 177–578), testosterone (20. 16 nmol/l; normal 0. 31–1. 94), and DHEA-S levels. MRI suggested a malignant adrenal tumor. She underwent an adrenalectomy, which confirmed an adrenocortical carcinoma (pT2N0). Postoperatively, she required hydrocortisone replacement, and further genetic testing identified a pathogenic TP53 variant, confirming LFS. Adjuvant therapy with mitotane was initiated, but two months post-surgery, abdominal MRI revealed peritoneal metastases. A second surgery removed multiple metastatic lesions, followed by chemotherapy (mitotane, temozolomide, cyclophosphamide). Despite treatment, the disease progressed, with new hepatic and peritoneal metastases. Given limited therapeutic options, pembrolizumab was introduced alongside metyrapone for hypercortisolism control. However, the patient’s condition deteriorated, with persistent tumor progression. At 13 months post-diagnosis, she succumbed to the disease.

Discussion: ACC in children is often diagnosed late due to nonspecific symptoms. In this case, signs of Cushing’s syndrome and virilization were present but not initially recognized. The association with LFS underscores the importance of genetic screening in pediatric ACC cases, as TP53 mutations significantly impact prognosis and treatment strategies. Despite aggressive surgical and systemic therapy, prognosis remains poor, particularly in metastatic disease. Mitotane remains the cornerstone of treatment, but novel approaches, including immunotherapy, are being explored. This case highlights the urgent need for better therapeutic strategies for pediatric ACC, particularly in genetically predisposed patients.

Conclusion: This case illustrates the aggressive nature of ACC in a child with LFS and the challenges in managing this rare malignancy. Early recognition, genetic testing, and novel treatment strategies are crucial for improving outcomes in pediatric ACC.

Keywords: Adrenocortical carcinoma, Li-Fraumeni syndrome, pediatric cancer, TP53 mutation, mitotane, immunotherapy.