Endocrine Abstracts

Background: Hypothalamic obesity (HO) is a rare but severe complication arising from hypothalamic injury, characterised by dysregulation of neuroendocrine circuits governing energy homeostasis, satiety, and metabolic rate. It is refractory to conventional lifestyle and pharmacological interventions, particularly in paediatric cohorts, for whom no regulatory-approved pharmacotherapy exists. Recent studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may modulate central appetite pathways and facilitate weight management; however, empirical evidence in paediatric HO remains limited.

Objective: To describe a single-centre observational experience utilising subcutaneous Semaglutide in four paediatric patients with syndromic or acquired forms of hypothalamic obesity, assessing anthropometric responses over a 12-month treatment period.

Methods: Four female patients (ages 12.7–18.9 years) with clinically and radiologically confirmed HO were commenced on Semaglutide therapy, titrated from 0.25–0.5 mg to a maximum of 2.4 mg weekly over 3–9 months. Aetiologies included septo-optic dysplasia, ROBO1-associated pituitary stalk interruption syndrome, non-metastatic intracranial germinoma, and Moebius syndrome with structural hypothalamic involvement. Longitudinal changes in body mass index (BMI) and BMI standard deviation score (SDS) were recorded at baseline, 6, and 12 months.

Results: The cohort’s mean baseline BMI was 50.3 ± 8.03 kg/m², with a mean BMI SDS of 4.21 ± 0.5. Two patients demonstrated clinically meaningful reductions in BMI and BMI SDS (maximum decrease: 16.8% weight loss with 0.62 BMI SDS reduction at 12 months). One patient experienced a relative attenuation of pre-treatment weight velocity, while another exhibited weight gain initially, followed by stabilisation. Individual variability in response was observed across both dosing trajectories and phenotypic context. No participants experienced severe adverse effects or treatment discontinuation.

Conclusion: This real-world series provides preliminary evidence that Semaglutide may facilitate BMI reduction or stabilisation in paediatric patients with HO, a notoriously treatment-resistant condition. Observed heterogeneity in response underscores the need for mechanistic studies investigating differential drug efficacy in relation to hypothalamic integrity, genetic background, and neuroendocrine phenotype. Further prospective randomised controlled trials are warranted to establish efficacy, durability, and safety of GLP-1RAs in the paediatric HO population.