MON-705 - Setmelanotide in Acquired Hypothalamic Obesity Following Childhood Craniopharyngioma: A Case Report

Background
Acquired hypothalamic obesity (HO) is a severe and frequently treatment-resistant complication of hypothalamic damage, most commonly following craniopharyngioma surgery. Disruption of melanocortin signaling, particularly impaired melanocortin-4 receptor (MC4R) activity, contributes to hyperphagia, reduced energy expenditure, and rapid weight gain. Setmelanotide, a selective MC4R agonist, has demonstrated efficacy in clinical trials of hypothalamic obesity, but real-world clinical experience remains limited.
Case Presentation
A 32-year-old man was evaluated for severe obesity. His medical history included surgical resection of a craniopharyngioma at age 11, followed by hypopituitarism and diabetes insipidus. Since childhood, he experienced persistent hyperphagia and progressive weight gain consistent with acquired hypothalamic obesity. The patient was receiving stable hormone replacement therapy with modified-release
hydrocortisone (Edicot®), desmopressin, levothyroxine, and human chorionic gonadotropin. Lifestyle interventions were ineffective. Prior pharmacologic therapy with tirzepatide resulted in minimal benefit, with persistent hyperphagia. Subcutaneous setmelanotide was initiated with gradual dose titration. During early treatment, a mild reduction in hyperphagic behavior was reported. Following dose
escalation, marked improvement in appetite regulation was observed, with fewer hunger episodes and improved satiety. A modest initial reduction in body mass index was followed by a total body weight loss of approximately 5% from baseline after completion of dose titration.
Treatment-related adverse events included transient nausea at initiation, which resolved after switching administration from morning to evening dosing, and mild skin hyperpigmentation. No serious adverse events occurred.
Conclusion
This case supports the potential role of MC4R agonism with setmelanotide as a targeted therapeutic approach in acquired hypothalamic obesity following childhood craniopharyngioma. Restoration of central melanocortin signaling may lead to clinically meaningful improvements in hyperphagia and body weight regulation in patients refractory to conventional and incretin-based therapies.
Keywords
Hypothalamic obesity; Craniopharyngioma; Melanocortin-4 receptor; Setmelanotide; Hyperphagia

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*