The management of hypothalamic obesity in craniopharyngioma.

Abstract

Hypothalamic obesity (HO) is a severe, treatment-refractory metabolic disorder resulting from hypothalamic injury secondary to craniopharyngioma directly or from its surgical resection. Characterised by dysregulated energy balance from disruption of complex hypothalamic neuroregulatory circuits, hyperphagia, and reduced sympathetic tone, HO arises due to impaired leptin-melanocortin signalling and autonomic dysfunction. Conventional lifestyle modifications remain largely ineffective, necessitating pharmacotherapeutic approaches targeting neuroendocrine and metabolic pathways. Amelioration of sleep disturbances and pituitary dysfunction serve as an important foundation for management of HO. The use of dextroamphetamine in some HO patients has proved effective. Emerging therapies include melanocortin-4 receptor (MC4R) agonists such as setmelanotide, which restore anorexigenic signalling, glucagon-like peptide-1 (GLP-1) receptor agonists that enhance satiety and energy expenditure, and combination strategies integrating adrenergic modulation (Tesomet). Despite promising preliminary data, long-term efficacy and safety profiles require further validation. Optimizing precision medicine approaches incorporating polypharmacotherapy and neuroendocrine modulation may redefine therapeutic paradigms for HO management.