ESPE Abstracts

Background: Hypothalamic obesity (HO), defined as abnormal weight gain due to physical hypothalamic destruction, for example due to suprasellar tumours, is characterised by significant hyperphagia, lack of satiety, and rapid weight gain in the first year of hypothalamic insult. HO is not usually responsive to caloric restriction or lifestyle modification, and no pharmacotherapies are specifically approved for treating HO. GLP-1 agonists, which suppress appetite via decreased gastric emptying and stimulation of hypothalamic satiety centres are licensed for obesity but their efficacy in HO is uncertain.

Case series: We commenced six patients (50% female; aged 13-18 years) with HO secondary to suprasellar tumours on GLP-1 agonists (liraglutide or semaglutide). At initiation of therapy, mean BMI was 36.7kg/m2 (±3.9) with mean BMI-SDS score of 3.24 ± 0.5. Complications of excess weight included obstructive sleep apnoea requiring overnight non-invasive ventilatory support in two patients and one patient had type 2 diabetes mellitus. Case 1 (female, craniopharyngioma) commenced on liraglutide (maximum 3 mg daily) aged 13.4 years (treatment duration 15 months), lost 3.2% of bodyweight (BMI-SDS reduction -0.14) after 3 months, which was sustained at 6 months (8.3% weight loss; -0.44 BMI SDS-reduction) and 12 months (11.8% weight loss; -0.63 BMI-SDS reduction) respectively. Case 2 (female, Rathke’s cleft cyst) commenced on liraglutide (maximum 3mg daily) aged 12.6 years, and gained 13.8% of bodyweight (+0.08 BMI-SDS increase) after 12 months treatment. She was switched to semaglutide (maximum 2mg weekly) and her weight stabilised with only 0.61% weight gain after 12 months corresponding to a BMI-SDS reduction of -0.32. Case 3 (male, craniopharyngioma) commenced on liraglutide (maximum 3 mg daily) aged 16.2 years (treatment duration 17 months) lost 4.1% of bodyweight (BMI-SDS reduction -0.24) after 3 months, which continued at 6 months (7.0% weight loss; -0.41 BMI SDS-reduction) and 12 months (8.6% weight loss; -0.63 BMI-SDS reduction) respectively. Encouraged by the results from these patients, a further three patients (two with pituitary germ cell tumours; one with craniopharyngioma) have recently been commenced on GLP-1 therapy but auxological follow-up data is awaited. All six patients report reduction in appetite and pre-occupation with food.

Conclusion: Response to GLP-1 therapy in HO is variable but initial results are encouraging in our cohort. More data are required to evaluate its use for treating hypothalamic obesity and associated metabolic sequelae. Consideration is warranted as to whether weight stabilisation, rather than loss, reflects a successful treatment outcome in this challenging patient cohort.