Pediatric low-grade gliomas and puberty: recognizing the subtle hormonal influence

Pediatric low-grade gliomas (pLGGs) are the most common central nervous system tumors in children and display an excellent overall survival but highly variable patterns of growth and endocrine morbidity. Emerging evidence suggests that puberty and sex steroid hormones may modulate tumor behavior, particularly for lesions involving the hypothalamic–pituitary axis, yet this interaction remains poorly characterized. This thesis aimed to explore the relationship between pubertal development and pLGG, focusing on the timing of tumor onset, the occurrence of precocious puberty, and the potential impact of hormone-suppressive therapies on tumor dynamics. We conducted a retrospective observational study including 301 patients aged 1 month to 18 years with histologically confirmed WHO grade 1–2 gliomas and at least 12 months of clinical, radiological, and endocrine follow-up. Pubertal status was assessed by Tanner staging and serum levels of luteinizing hormone, follicle-stimulating hormone, estradiol, and testosterone, while tumor course was evaluated with serial magnetic resonance imaging according to RAPNO criteria. Patients were stratified into early/prepubertal (Tanner ≤3) and advanced pubertal (Tanner >3) groups, and the incidence of precocious puberty, event-free survival, and radiologic progression were compared using Kaplan–Meier analysis and multivariate Cox regression adjusting for age, sex, tumor location, histology, and treatment. In this cohort, cerebellar (35%) and supratentorial hemispheric (32%) tumors predominated, with pilocytic astrocytoma representing 55% of cases and frequent MAPK-pathway alterations, including BRAF mutations and KIAA–BRAF fusions. Pubertal disturbances, particularly precocious puberty in patients with optic pathway and hypothalamic tumors, were observed and appeared temporally associated with tumor presentation and, in a subset of cases, with disease progression. Preliminary analyses suggest that pubertal status may act as a subtle but clinically relevant modifier of pLGG behavior and support the hypothesis that hormonal milieu could influence tumor growth trajectories. These findings highlight the need to systematically integrate endocrine assessment into pLGG follow-up, to refine risk stratification, and to prospectively evaluate the role of hormone-modulating treatments as potential adjuncts in selected patients