Prolonged symptom duration and the potential for gradual progression in pediatric adrenocortical tumors: observations from the MET studies

OBJECTIVES: To explore the clinical spectrum and symptom duration in pediatric adrenocortical tumors (pACTs), with a focus on identifying cases that may reflect gradual tumor progression. METHODS: We retrospectively analyzed data from 110 pediatric patients with pACTs enrolled in the German Pediatric Oncology Hematology-Malignant Endocrine Tumor (GPOH-MET) studies (1997-2022). Endocrine symptom duration, histopathological classification, and clinical outcomes were assessed. Patients with symptom durations ≥2 standard deviations (SDs) from the mean were defined as outliers and evaluated for potential progression. RESULTS: The cohort included 31 patients with adrenocortical adenomas (ACAs), 12 with tumors of uncertain malignant potential (ACx), and 67 with adrenocortical carcinomas (ACCs). Seven patients (6.4 %) showed markedly prolonged symptom duration, including four with ACC. One representative case demonstrated a nearly 5-year course from initial androgen excess to metastatic ACC, with evolving biochemical features and a diagnostic urinary steroid profile indicative of adrenal tumor activity. CONCLUSIONS: A small subset of pACTs may present with prolonged endocrine symptoms, possibly reflecting gradual tumor evolution. While molecular validation is lacking, these findings support the need for early recognition and further research into the natural history of pACTs.