Endocrine Abstracts

Hypothalamic obesity (HO) in children is a rare but severe form of obesity resulting from damage to the hypothalamus, most commonly following surgery, radiotherapy, or tumour infiltration involving the hypothalamic region,particularly in cases of craniopharyngioma. The hypothalamus plays a central role in energy homeostasis, integrating peripheral signals such as leptin, insulin, ghrelin, and neuropeptides to regulate appetite, satiety, and metabolic rate. Disruption of this regulatory network leads to hyperphagia, reduced energy expenditure, autonomic imbalance, and impaired circadian rhythm of hormone secretion.

Pathophysiologically, HO is characterised by leptin resistance, hyperinsulinaemia, and impaired sympathetic tone. Damage to the ventromedial hypothalamus disrupts melanocortin signalling via the pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons, leading to unopposed orexigenic drive. Additionally, parasympathetic overactivity promotes insulin secretion and lipogenesis, while sympathetic suppression reduces thermogenesis and physical activity. These mechanisms collectively result in rapid, intractable weight gain that is poorly responsive to lifestyle interventions.

Children with HO often present with early-onset obesity, hyperphagia, and associated metabolic complications including insulin resistance, dyslipidaemia, and non-alcoholic fatty liver disease. Management remains challenging and requires a multidisciplinary approach, including pharmacological agents targeting appetite and metabolism (e.g., GLP-1 analogues, stimulants), behavioural support, and emerging neuromodulatory therapies. Early identification and intervention are critical to mitigate long-term cardiometabolic risk and improve quality of life.

HO represents a distinct clinical entity with complex neuroendocrine dysregulation, underscoring the future need for targeted therapies and longitudinal research to better understand its mechanisms and optimise care in affected children.