Endocrine Abstracts

Background: Hypothalamic obesity (HO), defined as abnormal weight gain due to physical hypothalamic destruction, is characterised by significant hyperphagia. HO is not usually responsive to dietary interventions. No pharmacotherapies are specifically approved for HO and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RA) is uncertain. Outcomes of bariatric surgery in adults with HO are variable. We describe a young person with HO and the different management strategies utilised.

Case: This 11-year-old female was referred to paediatric endocrinology with slowing of linear growth (height velocity 3^rd centile; BMI-SDS 1.66). Glucagon stimulation testing demonstrated deficiencies in growth hormone and adrenocorticotropic hormone requiring hormone replacement. A Rathke’s cleft cyst was found on pituitary magnetic resonance imaging and a trans-sphenoidal resection was performed due to potential risk of visual compromise. Post-operatively, the young person developed arginine vasopressin (AVP) deficiency and central hypothyroidism. Additionally, her weight increased exponentially (BMI 34.7 kg/m²; BMI-SDS 3.34 at 12.5 years) despite lifestyle interventions. A monogenic obesity panel detected no pathogenic variants. Obstructive sleep apnoea was diagnosed requiring nocturnal non-invasive ventilation. She also experienced significant fatigue and low mood. Liraglutide (maximum 3 mg daily) (GLP-1 RA) was commenced at 12.6 years for weight management but stopped after 13.8% weight gain (+0.08 BMI-SDS increase) at 12 months. Subsequent treatment with semaglutide (maximum 2 mg weekly), another GLP-1 RA, reduced hunger and enabled weight stabilisation (0.6% weight gain after 12 months; -0.32 BMI-SDS reduction).A laparoscopic sleeve gastrectomy was performed aged 15 years, with bariatric surgery considered the only remaining treatment option to control hunger and achieve weight loss. Semaglutide was discontinued prior to surgery and not recommenced. Despite initial 7.6% weight loss (-0.46 BMI-SDS reduction) after 3 months, at 6 months post-operatively her weight had increased by 4.4% (+ 0.17 BMI-SDS increase) with return of hyperphagia.

Conclusions: This case with HO and obesity-related complications showed some response to GLP-1 RA and bariatric surgery. More data are required to evaluate the use of pharmacotherapy and bariatric surgery for HO and associated sequelae in the paediatric population. Consideration is warranted as to whether weight stabilisation, rather than loss, reflects a successful treatment outcome in this challenging condition.