Hypothalamic obesity in pediatric vs. adult craniopharyngioma: mechanisms, management, and cardiometabolic outcomes
Abstract
Purpose: Hypothalamic obesity (HO) is a treatment-related complication in craniopharyngioma (CP) survivors that markedly impairs long-term health and quality of life. Although overall survival exceeds 90% for both pediatric and adult CP, HO prevalence and clinical course differ substantially by age at onset. We aimed to compare HO manifestations, mechanisms, and treatment response between pediatric and adult CP cohorts.
Methods: We conducted a scoping review of studies published between 2000 and 2025, comparing pediatric (childhood-onset) versus adult-onset CP cohorts, classified by age at diagnosis. Data on obesity prevalence, mechanistic pathways, therapeutic interventions, and cardiometabolic outcomes were extracted and synthesized.
Results: In pediatric CP survivors, obesity rates rise from 5.7% pre-treatment to 57% post-treatment; in adults, from 19.2% to 29.2%. HO severity correlates with the extent of hypothalamic damage by Puget and QST grading. Key mechanisms include disrupted melanocortin signaling, central leptin and insulin resistance, and neuroinflammation via resistin-TLR4 and NLRP3 pathways. GLP-1 receptor agonists (exenatide, semaglutide) have produced marked weight loss in small case series (up to 17% over 6 months with semaglutide), but randomized trials did not meet their primary weight outcomes and direct pediatric-versus-adult comparisons are lacking. Bariatric procedures yield moderate success; sleeve gastrectomy achieves 5-year weight loss comparable…
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