Hypothalamic obesity (HO) is a significant, treatment-related complication in survivors of craniopharyngioma (CP) that impairs long-term health and quality of life. This article summarizes a scoping review of literature published from 2000 to 2025 that compared childhood-onset (pediatric) and adult-onset CP cohorts to delineate differences in HO prevalence, underlying mechanisms, treatment responses, and cardiometabolic outcomes.
The review focused on reported rates of obesity before and after treatment, mechanistic pathways implicated in HO, available therapeutic interventions and their reported effectiveness, and the long-term metabolic and mortality consequences in both age-defined cohorts.
Overall survival for craniopharyngioma exceeds 90% in both pediatric and adult populations, but the development and trajectory of HO differ markedly by age at diagnosis. In pediatric CP survivors, obesity prevalence increased from 5.7% before treatment to 57% after treatment. In adult-onset CP cohorts, obesity rates rose from 19.2% pre-treatment to 29.2% post-treatment. These figures highlight a substantially larger post-treatment obesity burden in childhood-onset disease compared with adult-onset disease, as reported in the reviewed literature.
Multiple mechanistic pathways contribute to HO after CP. Central disruption of energy-balance signaling is prominent, including derangements in melanocortin signaling and central leptin and insulin resistance. The review also emphasizes hypothalamic neuroinflammation as an important driver of metabolic dysfunction in this population, with implicated pathways including resistin-TLR4 signaling and activation of the NLRP3 inflammasome. Together, these mechanisms produce dysregulated appetite control, altered energy expenditure, and impaired peripheral metabolic regulation that underlie rapid weight gain in many survivors.
Severity of HO correlates with the extent of hypothalamic injury as assessed by established grading systems. The review cites associations between HO severity and hypothalamic damage graded by Puget and QST systems. These radiologic or operative grading tools help predict risk for subsequent HO and guide expectations for metabolic outcomes after therapy.
Pharmacologic options studied in HO after CP include agents targeting appetite and metabolic regulation. The review highlights GLP-1 receptor agonists such as exenatide and semaglutide. Small case series reported marked weight loss with these agents, with semaglutide described as producing weight reductions up to approximately 17% over 6 months in some reports. However, randomized trials in this population did not meet their primary weight outcomes. Additionally, the literature lacks direct comparative data on pharmacologic responses between pediatric and adult CP cohorts, limiting age-specific treatment conclusions.
Bariatric procedures have been used for refractory HO after CP. Reported outcomes are mixed by procedure type. Sleeve gastrectomy achieved 5-year weight loss comparable to non-CP controls (21.7% vs. 21.8%), whereas Roux-en-Y gastric bypass yielded less favorable results than controls (22.7% vs. 32.0%). The review synthesizes available evidence but notes that direct pediatric-versus-adult comparisons and randomized data are lacking, and that patient selection and hypothalamic injury severity likely influence surgical outcomes.
Both pediatric and adult CP survivors face considerable long-term cardiometabolic risk. In adults, the literature reports a 2.2-fold higher all-cause mortality and a 9.3-fold higher risk of diabetes compared with reference populations. Among pediatric survivors, non-alcoholic fatty liver disease was reported in approximately 47%, and insulin resistance affected roughly 30% of patients. In adult cohorts, metabolic dysfunction-associated fatty liver disease was observed in 67.4%. These findings underscore a substantial burden of metabolic disease after CP-associated hypothalamic injury.
The scoping review concludes that HO following CP exhibits distinct, age-dependent trajectories in prevalence, pathophysiology, and clinical course. Although mechanistic understanding has advanced—particularly regarding melanocortin pathway disruption, central leptin/insulin resistance, and hypothalamic neuroinflammation—evidence for age-specific differences in treatment efficacy remains limited.
Notably, promising signals for GLP-1 receptor agonists come from small series, but randomized trials have not uniformly met primary weight endpoints, and direct comparisons between pediatric and adult responses are absent. Bariatric surgery can be effective in selected patients, with variable outcomes by procedure type.
The authors emphasize the need for tailored management strategies that integrate mechanistic insights and age-appropriate therapies to reduce the substantial cardiometabolic burden in CP survivors. They call for direct comparative studies, larger controlled trials of pharmacologic agents in HO, and longitudinal follow-up focused on metabolic outcomes to better inform age-specific clinical decision-making.