Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Case:

A 36-year-old male developed pan-hypopituitarism following debulking of a papillary craniopharyngioma (CP). Serial post-operative magnetic resonance imaging scans demonstrated complete tumour resection with no recurrence. Within five weeks of surgery, our patient had gained 15.1kg (Table 1). The trend persisted despite a low-calorie diet and optimising pituitary hormone replacement (Figure 1). By eight months, he had gained 38.6kg(BMI 36 kg/m²) and was diagnosed with obstructive sleep apnoea. Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), was commenced. After four months, 11% weight loss had been achieved on a maximally tolerated dose of 2.4mg subcutaneous daily.

Discussion:

The hypothalamus is the master regulator of energy homeostasis and appetite signalling^1,2. Acquired hypothalamic obesity (AHO) is characterised by accelerated weight gain following structural damage to the hypothalamus and is challenging to treat^1,3. CPs are the most common cause either due to the tumour itself or its management with surgery or radiotherapy^1,2.

There are no approved pharmacotherapies for AHO, though various options are being explored⁵. GLP-1RAs achieve weight loss through early satiety signals and delayed gastric emptying⁶. They present a novel option as their mechanism of action can circumvent the hypothalamus – they also bind to appetite-related centres in the hindbrain⁵.

Whilst a recent systematic review by Vu et.al⁸ and case reports on longer-acting GLP-1RAs have demonstrated promising results, a spectrum of responses have been reported^2,6-9. The heterogeneity could reflect the varying degree of damage to the hypothalamus, which could be used to stratify patients who may benefit from GLP-1RAs^2,3,5.

Due to the multi-faceted weight gain in AHO, a combination of treatment modalities will likely be required^5,9. Preliminary studies support the use of GLP-1RAs, but long-term efficacy remains unknown⁸. Regardless, early recognition of AHO especially post CP resection is important and effective intervention is crucial to mitigate excessive weight gain and associated morbidity.