Endocrine disorders after treatment for pediatric brain tumors: long-Term outcomes and risk factors.
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PURPOSE: Survivors of childhood brain tumors are at high risk of hypothalamic-pituitary dysfunction, but comparative data across cancer histotypes and treatment modalities are limited. This study evaluated the prevalence, risk factors, and timing of onset of hypothalamic-pituitary disorders in a large cohort of childhood brain cancer survivors, with attention to tumor type and therapeutic exposure. METHODS: A retrospective cohort of 388 patients diagnosed with primary brain tumors before 18 years of age and followed at a tertiary center between 2000 and 2025 was analyzed. Demographic, clinical, and treatment data were extracted from medical records. Standardized endocrine assessments, including dynamic testing when indicated, were performed at diagnosis and throughout follow-up. Endocrine disorders were classified by international criteria, and onset timing was recorded. RESULTS: Glioma was the most frequent histotype (66.2%), followed by medulloblastoma (19.1%), ependymoma (6.2%), craniopharyngioma (5.2%), and germ-cell tumors (3.3%). Endocrine disorders occurred in 75.8% of patients, with the highest prevalence in craniopharyngioma and germ-cell tumors. Central hypothyroidism (27.8%) was the most common deficiency, followed by central precocious puberty (27.1%), growth hormone deficiency (25.8%), adrenocorticotropic hormone deficiency (22.7%), and central diabetes insipidus (16.8%). Early-onset deficiencies were typically related to surgical hypothalamic-pituitary injury, whereas late-onset disorders were mainly associated with radiotherapy or chemotherapy. Younger age at diagnosis and sellar/suprasellar localization independently predicted endocrine morbidity. CONCLUSION: This study provides a comprehensive analysis of endocrine outcomes by tumor histotype, treatment modality, and onset timeline, underscoring the need for individualized and lifelong endocrine surveillance in survivors of childhood brain tumors.