---
title: "Hypothalamic obesity after craniopharyngioma: pediatric vs adult differences in mechanisms, treatm"
id: "pubmed-42801380"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42801380"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42801380/"
doi: "10.1007/s11102-026-01760-z"
published_at: "2026-09-27T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Hypothalamic obesity after craniopharyngioma: pediatric vs adult differences in mechanisms, treatm
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42801380
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42801380/)
- **DOI:** [10.1007/s11102-026-01760-z](https://doi.org/10.1007%2Fs11102-026-01760-z)
- **Published At:** 2026-09-27T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Hypothalamic obesity (HO) is a common, treatment-related complication after **craniopharyngioma (CP)** that substantially worsens long-term health and quality of life despite overall CP survival exceeding 90% in both pediatric and adult cohorts. - This scoping review included studies published between 2000 and 2025 comparing childhood-onset (pediatric) versus adult-onset CP to summarize prevalence, mechanisms, treatment responses, and cardiometabolic sequelae. - Prevalence and severity of HO differ by age: pediatric CP survivors show an increase in obesity from 5.7% pre-treatment to 57% post-treatment; adult-onset CP increases from 19.2% to 29.2%. - Severity of HO correlates with the extent of hypothalamic damage as assessed by **Puget** and **QST grading** systems. - Key mechanistic contributors identified include disrupted **melanocortin signaling**, central **leptin** and **insulin resistance**, and hypothalamic **neuroinflammation** mediated by resistin-TLR4 and **NLRP3** inflammasome pathways. - Pharmacologic interventions evaluated include **GLP-1 receptor agonists** (eg, exenatide, semaglutide), which produced notable weight loss in small case series (reports up to ~17% over 6 months with semaglutide), but randomized trials failed to meet primary weight endpoints and direct pediatric-versus-adult comparisons are lacking. - Bariatric surgery shows mixed results: sleeve gastrectomy produced 5-year weight loss similar to non-CP controls (21.7% vs 21.8%), while Roux-en-Y gastric bypass was less effective than controls (22.7% vs 32.0%). - Long-term cardiometabolic risks are substantial: adults with CP have a reported 2.2-fold higher all-cause mortality and a 9.3-fold higher diabetes risk; pediatric survivors show high rates of non-alcoholic fatty liver disease (~47%) and insulin resistance (~30%), while adults show metabolic dysfunction-associated fatty liver disease in 67.4%. - The review concludes that HO after CP follows distinct, age-dependent trajectories in prevalence, mechanisms, and clinical course; evidence for age-specific differences in treatment response is suggestive but requires direct comparative studies. - The authors emphasize the need for tailored management integrating mechanistic insights and age-appropriate therapies to reduce the cardiometabolic burden in CP survivors.
## Clinical Analysis & Structured Key Points
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Davidoff Department of Neurological Surgery, Albert Einstein College of Medicine, Montefiore Einstein, 111 East 210th Street, New York, NY, 10467, USA. khushal.gupta@einsteinmed.edu."), [Maryam Zeinali](https://pubmed.ncbi.nlm.nih.gov/?term=Zeinali+M&cauthor_id=42801380)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42801380/#full-view-affiliation-2 "Mazandaran University of Medical Sciences, Sari, Iran."), [David Altschul](https://pubmed.ncbi.nlm.nih.gov/?term=Altschul+D&cauthor_id=42801380)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42801380/#full-view-affiliation-3 "The Leo M. Davidoff Department of Neurological Surgery, Albert Einstein College of Medicine, Montefiore Einstein, 111 East 210th Street, New York, NY, 10467, USA."), [Vijay Agarwal](https://pubmed.ncbi.nlm.nih.gov/?term=Agarwal+V&cauthor_id=42801380)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42801380/#full-view-affiliation-3 "The Leo M. Davidoff Department of Neurological Surgery, Albert Einstein College of Medicine, Montefiore Einstein, 111 East 210th Street, New York, NY, 10467, USA."), [Michael Karsy](https://pubmed.ncbi.nlm.nih.gov/?term=Karsy+M&cauthor_id=42801380)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42801380/#full-view-affiliation-4 "Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.") Affiliations Expand ### Affiliations * 1 The Leo M. Davidoff Department of Neurological Surgery, Albert Einstein College of Medicine, Montefiore Einstein, 111 East 210th Street, New York, NY, 10467, USA. khushal.gupta@einsteinmed.edu. * 2 Mazandaran University of Medical Sciences, Sari, Iran. * 3 The Leo M. Davidoff Department of Neurological Surgery, Albert Einstein College of Medicine, Montefiore Einstein, 111 East 210th Street, New York, NY, 10467, USA. * 4 Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA. * PMID: **42801380** * DOI: [ 10.1007/s11102-026-01760-z ](https://doi.org/10.1007/s11102-026-01760-z) Item in Clipboard Review # Hypothalamic obesity in pediatric vs. adult craniopharyngioma: mechanisms, management, and cardiometabolic outcomes Khushal Gupta et al. Pituitary. 2026. Show details Display options Display options Format Abstract PubMed PMID Pituitary Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Pituitary%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Pituitary%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42801380/) . 2026 Sep 27;29(5):161. doi: 10.1007/s11102-026-01760-z. ### Authors [Khushal Gupta](https://pubmed.ncbi.nlm.nih.gov/?term=Gupta+K&cauthor_id=42801380)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42801380/#short-view-affiliation-1 "The Leo M. Davidoff Department of Neurological Surgery, Albert Einstein College of Medicine, Montefiore Einstein, 111 East 210th Street, New York, NY, 10467, USA. khushal.gupta@einsteinmed.edu."), [Maryam Zeinali](https://pubmed.ncbi.nlm.nih.gov/?term=Zeinali+M&cauthor_id=42801380)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42801380/#short-view-affiliation-2 "Mazandaran University of Medical Sciences, Sari, Iran."), [David Altschul](https://pubmed.ncbi.nlm.nih.gov/?term=Altschul+D&cauthor_id=42801380)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42801380/#short-view-affiliation-3 "The Leo M. Davidoff Department of Neurological Surgery, Albert Einstein College of Medicine, Montefiore Einstein, 111 East 210th Street, New York, NY, 10467, USA."), [Vijay Agarwal](https://pubmed.ncbi.nlm.nih.gov/?term=Agarwal+V&cauthor_id=42801380)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42801380/#short-view-affiliation-3 "The Leo M. Davidoff Department of Neurological Surgery, Albert Einstein College of Medicine, Montefiore Einstein, 111 East 210th Street, New York, NY, 10467, USA."), [Michael Karsy](https://pubmed.ncbi.nlm.nih.gov/?term=Karsy+M&cauthor_id=42801380)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42801380/#short-view-affiliation-4 "Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.") ### Affiliations * 1 The Leo M. Davidoff Department of Neurological Surgery, Albert Einstein College of Medicine, Montefiore Einstein, 111 East 210th Street, New York, NY, 10467, USA. khushal.gupta@einsteinmed.edu. * 2 Mazandaran University of Medical Sciences, Sari, Iran. * 3 The Leo M. Davidoff Department of Neurological Surgery, Albert Einstein College of Medicine, Montefiore Einstein, 111 East 210th Street, New York, NY, 10467, USA. * 4 Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA. * PMID: **42801380** * DOI: [ 10.1007/s11102-026-01760-z ](https://doi.org/10.1007/s11102-026-01760-z) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## 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 to that in non-CP controls (21.7% vs. 21.8%), whereas Roux-en-Y gastric bypass is less effective than in controls (22.7% vs. 32.0%). Both cohorts face significant long-term risks: 2.2-fold higher all-cause mortality and 9.3-fold higher diabetes risk in adults, non-alcoholic fatty liver disease in 47% of pediatric survivors, metabolic dysfunction-associated fatty liver disease in 67.4% of adults, and insulin resistance in approximately 30% of pediatric patients. **Conclusion:** HO following CP shows distinct age-dependent trajectories in prevalence, underlying mechanisms, and clinical course; suggested age-related differences in treatment response remain to be confirmed in direct comparative studies. Tailored management integrating mechanistic insights and age-specific therapies is critical to mitigating the cardiometabolic burden in these patients. **Keywords:** Cardiometabolic outcomes; Craniopharyngioma; GLP-1 receptor agonists; Hypothalamic obesity; Neuroinflammation; Pediatric. © 2026. The Author(s). [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Ethics approval: Not applicable. This article is a scoping review of previously published literature and did not involve human participants, animal subjects, or identifiable patient data. Consent to participate: Not applicable. Consent to publish: Not applicable. Generative artificial intelligence use: Generative artificial intelligence was used to assist with language editing, formatting, and citation consistency checking during the preparation of this manuscript. All scientific content and citations were reviewed and verified by the authors, who take full responsibility for the integrity of the work. Competing interests: The authors declare no competing interests. ## References 1. 1. Sterkenburg AS, Hoffmann A, Gebhardt U, Warmuth-Metz M, Daubenbüchel AMM, Müller HL (2015) Survival, hypothalamic obesity, and neuropsychological/psychosocial status after childhood-onset craniopharyngioma: newly reported long-term outcomes. Neuro Oncol 17(7):1029–1038. - [DOI](https://doi.org/10.1093/neuonc/nov044) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/25838139/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/5654354/) 2. 1. Craven M, Crowley JH, Chiang L, Kline C, Malbari F, Hocking MC et al (2022) A survey of patient-relevant outcomes in pediatric craniopharyngioma: focus on hypothalamic obesity. Front Endocrinol 13:876770. - [DOI](https://doi.org/10.3389/fendo.2022.876770) 3. 1. Wu W, Sun Q, Zhu X, Xiang B, Zhang Q, Miao Q et al (2021) Risk factors for hypothalamic obesity in patients with adult-onset craniopharyngioma: a consecutive series of 120 cases. Front Endocrinol 12:694213. - [DOI](https://doi.org/10.3389/fendo.2021.694213) 4. 1. Park SW, Jung HW, Lee YA, Shin CH, Yang SW, Cheon JE (2013) Tumor origin and growth pattern at diagnosis and surgical hypothalamic damage predict obesity in pediatric craniopharyngioma. J Neuro Oncol 113(3):417–424. - [DOI](https://doi.org/10.1007/s11060-013-1128-0) 5. 1. Roth CL, Zenno A (2023) Treatment of hypothalamic obesity in people with hypothalamic injury: new drugs are on the horizon. Front Endocrinol 14:1256514. - [DOI](https://doi.org/10.3389/fendo.2023.1256514) Show all 135 references ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42801380/) ## MeSH terms * Adult Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Adult%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Adult) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42801380/) * Child Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Child%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Child) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42801380/) * Craniopharyngioma* / complications Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Craniopharyngioma%2Fcomplications%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Craniopharyngioma) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42801380/) * Craniopharyngioma* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Craniopharyngioma%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Craniopharyngioma) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42801380/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42801380/) * Hypothalamic Diseases* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Hypothalamic+Diseases%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Hypothalamic+Diseases) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42801380/) * Hypothalamus* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Hypothalamus%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Hypothalamus) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42801380/) * Obesity* / etiology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Obesity%2Fetiology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Obesity) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42801380/) * Obesity* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Obesity%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Obesity) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42801380/) * Obesity* / therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Obesity%2Ftherapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Obesity) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42801380/) * Pituitary Neoplasms* / complications Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Pituitary+Neoplasms%2Fcomplications%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Pituitary+Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42801380/) * Pituitary Neoplasms* / metabolism Actions * [ Search in PubMed ](https
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