Current Approaches and Therapeutic Strategies for Hypothalamic Syndrome in Patients with Childhood-onset Craniopharyngioma

Patients diagnosed with craniopharyngioma often experience rapid and pronounced weight gain that can progress to severe hypothalamic obesity. This phenomenon is predominantly attributed to disruption of critical hypothalamic regulatory circuits, caused either by direct tumor infiltration or by treatment-related injury. Hypothalamic obesity is best conceptualized within the broader framework of hypothalamic syndrome, a complex clinical disorder encompassing multiple neuroendocrine deficits, impairments in circadian homeostasis, dysregulation of hunger, satiety, and thirst mechanisms, disturbances in thermoregulatory control, and a wide range of cognitive, sleep-related, and psychosocial abnormalities. Hypothalamic syndrome may also develop secondary to nonmalignant parasellar pathologies, including germ cell tumors, gliomas, Rathke's cleft cyst, and Langerhans cell histiocytosis, as well as traumatic hypothalamic injury following traumatic brain insult. Long-term prognosis is frequently poor, driven by elevated risks of metabolic syndrome, cardiovascular disease, diminished health-related quality of life, and increased rates of premature mortality. Management remains particularly challenging. Recently, a personalized and risk-stratified therapeutic framework has been proposed to guide clinical decision-making and optimize outcomes. Several pharmacologic interventions, such as centrally acting stimulants, glucagon-like peptide-1 receptor agonists, and the melanocortin-4 receptor agonist setmelanotide, have demonstrated potential in promoting weight reduction. Bariatric surgery may also yield clinical benefit; however, the use of irreversible procedures in pediatric populations presents substantial ethical and legal challenges. There remains an urgent need for therapeutic strategies that emphasize preservation of hypothalamic structure and function, alongside continued research into targeted and emerging interventions for more effective management of hypothalamic syndrome.