Clinical characteristics and endocrine outcomes of functional and nonfunctional adrenal lesions in children: a single-center cohort study.

Abstract

Objectives: Pediatric adrenal lesions are rare and clinically heterogeneous and present with hormonally active or inactive phenotypes. Functional lesions may cause significant endocrine morbidity. This study aimed to evaluate the clinical, biochemical, radiological, and pathological characteristics of pediatric adrenal lesions and to determine which findings obtained during the initial diagnostic evaluation may help distinguish functional from nonfunctional lesions.

Methods: This retrospective single-center cohort study included children evaluated for adrenal lesions between January 2020 and June 2025. Patients were classified as having functional or nonfunctional lesions on the basis of clinical and biochemical evidence of hormonal activity. Demographic features, hormonal profiles, imaging findings, pathological characteristics, treatment modalities and follow-up outcomes were analysed.

Results: A total of 44 patients were included; 12 (27.3 %) had functional lesions, and 32 (72.7 %) had nonfunctional lesions. The tumor size was significantly larger for functional lesions (median 54.0 vs. 19.0 mm, p<0.001). Premature pubarche, clitoromegaly, cushingoid features and hypertension were more common in the functional group. Tumor size was positively correlated with total testosterone levels, and the bone age-to-chronology age ratio was associated with several hormonal parameters. Distinct clinical manifestations, including premature pubarche, virilization, cushingoid features, and hypertension, were predominantly observed in functional lesions. Germline pathogenic variants were identified in three patients with adrenocortical carcinoma (TP53) and in one patient with pheochromocytoma (VHL).

Conclusions: Functional adrenal lesions in the pediatric population are characterized by a relatively large tumor size, distinct hormonal secretion patterns, and specific clinical manifestations. Key findings obtained during the initial diagnostic evaluation can facilitate early differentiation between functional and nonfunctional lesions, thereby supporting more accurate clinical stratification and informing optimal management strategies.