Endocrine Abstracts

JOINT1885

Introduction: Hypothalamic obesity (HO) is a rare and severe form of obesity due to hypothalamic damage, often resulting from neurosurgical interventions. It is characterized by alterations in food control mechanisms and decreased energy expenditure, resulting in refractory weight gain. HO is unresponsive to conventional weight loss strategies like lifestyle modifications, pharmacotherapy, and bariatric surgery. GLP-1 receptor agonists (GLP-1RAs) represent a successful pharmacological paradigm to treat general obesity delaying gastric emptying and improving satiety by multiple mechanisms. We present three cases of HO successfully treated with off-label weekly semaglutide.

Case 1: A 36-year-old female with panhypopituitarism and diabetes insipidus secondary to multiple craniopharyngioma surgeries developed severe HO. She reached a maximum weight of 138.5kg (BMI 44.7), that was managed with sleeve gastrectomy in 2017. Her weight dropped to 119kg but gradually returned to 138kg (June 2024). At this point we started semaglutide (0.25mg to 2.4mg). The result was a 16kg weight loss (-11.6%) reaching 122kg (BMI 39.4) in just six months (date of the last visit).

Case 2: An 18-year-old male with panhypopituitarism and diabetes insipidus post-craniopharyngioma surgery in 2020 developed HO. Before surgery, he weighed 75kg (BMI 28.6) dropped to 54kg due to hyporexia. After surgery, he rapidly gained weight, reaching 97kg (July 2021) and 123kg (BMI 46.9) by June 2022. Semaglutide (0.25mg to 2mg) led to a 26.8% weight loss, reaching 91kg by March 2023, weight maintained to this day. He reported improved appetite control and no significant adverse effects.

Case 3: A 16-year-old female with panhypopituitarism following craniopharyngioma double resection (2019, 2020) developed HO, with weight increasing from 51.2kg (BMI 22.5) to 75kg (BMI 33.0). Due to progressive and refractory weight gain, semaglutide was started in 2023 (0.25mg to 1mg), leading to significant weight reduction (-27.3%), reaching 54.5kg (BMI 24.8) by December 2023. By January 2025, her weight stabilized at 62kg (BMI 28.5). The only side effect was mild nausea.

Discussion: Although GLP-1RAs’ efficacy is well-documented in general obesity, their role in HO remains under investigation. These cases align with recent real-world studies, showing significant weight loss with semaglutide, alongside improved appetite regulation. Long-term treatment appeared necessary to maintain weight loss. Semaglutide’s effects could extend beyond hypothalamic signalling, involving extrahypothalamic pathways such as the brainstem and vagus nerve. Advances in obesity treatment, including dual and tri-agonists, could represent a promising approach for achieving significant weight loss and improved appetite control without major side effects even in HO patients.