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Purpose: Patients with hypothalamic pathology often develop hypothalamic obesity, causing severe metabolic alterations resulting in increased morbidity and mortality. Treatments for hypothalamic obesity have not proven very effective, although the glucagon-like peptide-1 receptor agonist semaglutide has been shown to have positive effects. We examined semaglutide's effect on weight loss in a sample of patients with hypothalamic obesity., Methods: Four female patients with hypothalamic obesity resulting from treatment of craniopharyngiomas were treated with semaglutide for six months. Whole Body Dual-energy x-ray absorptiometry scans were performed, and blood samples drawn at baseline and after six months. Semaglutide dosages were increased monthly along with tracking of body weight and eating behavior (Three Factor Eating Questionnaire, TFEQ-R18)., Results: BMI was reduced in all cases, with an average of 7.9 BMI (range: 6.7 to 10.1) corresponding to a weight loss of 17.0% (range: 11.3-22.4%) or 20.2 kg (range 16.2 kg to 23.4 kg). We found a comparable reduction in total fat mass (17.2%, p = 0.006) and lean mass (16.0%, p = 0.05), whereas bone mass was unchanged (2.6%, p = 0.12). All cases reported an increase in energy levels, improved mobility and physical activity. Unfavorable eating behaviors were reduced after 1 month of treatment (emotional eating - 41 points, p = 0.02, uncontrolled eating - 23 points, p = 0.11). HbA1c and total cholesterol were significantly reduced (p = 0.014 for both)., Conclusion: Semaglutide is a promising and safe treatment option for HO, that improves eating behavior, reduces weight, and improves metabolic markers., (© 2024. The Author(s).)

Purpose: Craniopharyngiomas (CPs) are rare tumors of the sellar region often leading to significant comorbidities due to their close proximity to critical structures. The aim of this study was to analyze survival outcome and late toxicities after surgery and proton beam therapy (PBT) in childhood CPs., Methods and Materials: Within the prospective registry study "KiProReg" (DRKS0000536), data of 74 childhood patients with CP, receiving PBT between August 2013 to June 2022 were eligible. Late toxicities were analyzed according to the grading system of the Common Terminology Criteria for Adverse Events, version 4.0., Results: Median follow-up since first diagnosis was 4.3 years (range, 0.8-14.7). In addition, 75.7% of patients received PBT at time of disease progression or recurrence, whereas 24.3% as part of their primary therapy (definitive or adjuvant). Predominantly (85.1%), pencil beam scanning technique was used. The median total dose and initial tumor volume were 5400 cGy relative biologic effectiveness (RBE) and 17.64 cm³ (range, 3.07-300.59), respectively. The estimated (±SE) 3-year overall survival, progression-free, and cystic failure-free survival rate after PBT were 98.2% (±1.7), 94.7% (±3.0), and 76.8% (±5.4), respectively. All local failures (n = 3) were in-field relapses necessitating intervention and occurred exclusively in patients receiving PBT at progression or recurrence. Early cystic enlargements after PBT were typically asymptomatic and self-limiting. Fatigue, headaches, vision disorders, obesity, and endocrinopathies were the predominant late toxicities. No high-grade (≥3) new-onset visual impairment or cognitive deterioration occurred compared with baseline. The presence of cognitive impairments at the end of follow-up correlated with size of the planning target volume (P = .034), D mean dose to the temporal lobes (P = .032, P = .045) and the number of surgical interventions before PBT (P = .029)., Conclusions: Our findings demonstrate favorable local control rates using modern PBT with acceptable late toxicities. Cyst growth within 12 months after radiation therapy is typically not associated with tumor progression. Longer follow-up must be awaited to confirm results., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hypothalamic obesity (HO) is defined as abnormal weight gain resulting in severe persistent obesity due to physical, tumor- and/or treatment-related damage to the hypothalamus. HO epidemiology is poorly understood. We developed a database algorithm supporting the standardized identification of tumor/treatment-related HO (TTR-HO) patients. The algorithm is used to estimate incidence rates of TTR-HO patients in the German healthcare context from a representative claims database (n = 5.42 million) covering 2010-2020. Patients were identified based on surgery/radiotherapy procedures and HO-associated tumor diagnoses (n = 3976). HO was defined by incident obesity and validated based on incident diabetes insipidus diagnoses and desmopressin prescription within a 12-month period after surgery/radiotherapy. Uncertainty due to algorithm definitions is explored in sensitivity analyses. Estimated annual incidence of TTR-HO in Germany is between 0.7 and 1.7 cases per 1,000,000 persons (2019 prevalence: n = 1262 patients). With observed cases in all age groups, two HO-incidence peaks are identified: children/young adults aged 10-24 years and adults aged 40-44 years. Most frequent HO-validated tumor diagnoses are benign sellar/suprasellar tumors (6.1/1,000,000 persons over 9 years), including tumors of the craniopharyngeal duct (1.3/1,000,000), neoplasms of the pituitary gland (4.1/1,000,000), and nonspecific brain tumors of endocrine glands (2.4/1,000,000). This is the first real-world database analysis of TTR-HO epidemiology, refining current estimates of HO epidemiology and early patient identification. A more comprehensive characterization of patients with HO as well as a better understanding of clinical implications will be crucial in developing optimal treatment strategies to improve patient outcomes., (© 2024 The Author(s). Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Background: Craniopharyngiomas (CP) are histologically benign (WHO grade 1), embryonal malformations which are related to remnants of the Rathke's pouch and are located in the (peri)sellar region. Already before CP diagnosis, many patients show a reduced growth velocity and tend to present with weight gain. However, it is unknown whether patients with CP develop an increased head circumference (HC) before CP diagnosis, which could be a useful early diagnostic indicator., Patients and Methods: For a cohort of 83 patients recruited in the multicenter studies KRANIOPHARYNGEOM 2000 and HIT-ENDO data on HC could be analyzed, based on medical records assessed in developmental monitoring visits performed at defined time points before CP diagnosis., Results: When comparing HC standard deviation scores (SDS) before CP diagnosis in 83 patients at defined time points between birth and 4 years of age, all HC were in the upper normal range. However, CP patients diagnosed at an age ≤4 years with initial hypothalamic involvement presented with a tendency towards an increased HC SDS early before CP diagnosis at routine medical examinations during the first 7 months of life., Conclusions: We conclude that monitoring of growth and weight development including HC can lead to early CP diagnosis and treatment. This might prevent higher grades of hypothalamic involvement and lead to an improvement of quality of life after CP. Further studies on the specific value of HC as a diagnostic marker are warranted., Competing Interests: H.L.M. has received reimbursement of participation fees for scientific meetings and continuing medical education events from the following companies: Ferring, Lilly, Pfizer, Sandoz/Hexal, Novo Nordisk, Ipsen, and Merck Serono. H.L.M. has received reimbursement of travel expenses from Ipsen and lecture honoraria from Pfizer. B.B. has received lecture honorarium from Merck Serono. The other authors declare that they have no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Beckhaus et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: It is well known that both genetic background and lifestyle influence the development of 'general' obesity. However, the role of parental body mass index (BMI) on the development of obesity in long-term survivors of childhood-onset craniopharyngioma (CP) is not well understood. This study analyzed the correlation of patients' BMI at diagnosis and last visit and parental BMI at CP diagnosis and further explored potential risk factors for obesity in CP patients., Design: This is a registry-based retrospective cohort study., Methods: In total,291 CP patients and their parents recruited in the German KRANIOPHARYNGEOM studies were included. Correlations between patient's BMI SDS at CP diagnosis and last visit and parental BMI at CP diagnosis were analyzed. The associations between hypothalamic damage, maternal/paternal BMI and CP patients' obesity at last visit were analyzed by multivariable logistic regression., Results: At follow-up, 52% of CP patients developed obesity (BMI > 3SDS). Patient's BMI SDS at last visit was moderately correlated with BMI-SDS at CP diagnosis (r = 0.48, 95% CI: 0.38-0.58, P < 0.001), and also with maternal BMI at diagnosis (r = 0.28, 95% CI: 0.17-0.38, P < 0.001) and paternal BMI at diagnosis (r = 0.3, 95% CI: 0.19-0.41, P < 0.001). However, the contributing role of parental BMI to the pathogenesis of obesity was small compared to the impact of hypothalamic damage., Conclusion: We conclude that besides hypothalamic damage, parental disposition for obesity is associated with the development of obesity in patients after CP. Our results indicate that also the family situation could have an influence on the development of obesity after CP and might be a therapeutic target., Significance Statement: Survivors of childhood-onset craniopharyngioma are at risk of developing morbid obesity. So far, patients with posterior hypothalamic involvement and lesion were identified as a high risk group. With this study, the influence of parental body mass index on the risk of obesity was investigated. Patient's body-mass-index at last visit was correlated with maternal and paternal body mass index at diagnosis. With increasing maternal or paternal body mass index, the likelihood of obesity in individuals with CP increased. Nevertheless, the parents' weight had only a small effect on the development of patients' obesity compared to hypothalamic damage.

Competing Interests: HM has received reimbursement of participation fees for scientific meetings and continuing medical education events from the following companies: Ferring, Pfizer, Sandoz/Hexal, Novo Nordisk, IPSEN, and Merck Serono. He has also received reimbursement of travel expenses from Merck Serono, Rhythm Pharmaceuticals, and IPSEN and a lecture honoraria from Pfizer and Rhythm Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Craniopharyngioma (CP) treatment, including surgery and radiotherapy, can have short- and long-term vascular side effects. Hypothalamic damage is related to morbid obesity and may increase the lifelong risk of experiencing vascular events in CP patients. This review summarized the available evidence regarding vascular complications in adamantinomatous or papillary CP patients, whatever their age at diagnosis. Three databases (Medline, CINAHL, Web of Science) were searched (06/2023) to retrieve eligible articles. The search was limited to peer-reviewed articles. Titles, abstracts, and full texts were screened by two independent reviewers, and data were extracted using a self-developed grid. Seventy-two studies were included in this review; the majority were case reports. Reported vascular sequela that occurred due to surgery were fusiform dilation of the carotid artery, stroke, vasospasm, hemorrhage, and aneurysm. Related conditions that emerged due to radiotherapy included Moyamoya syndrome and cavernoma. Cardiovascular morbidity and mortality often lead to hypothalamic obesity and metabolic syndrome in CP patients. Vascular damage is a rare complication of CP treatment. Surgical strategies should protect the surrounding hypothalamic and vascular structures. Patients receiving radiotherapy, particularly at a young age, should undergo magnetic resonance angiography monitoring to identify possible neurovascular sequela during post-treatment care.