Abstract
Acquired hypothalamic obesity (aHO) is a disease characterized by rapid, clinically significant, and persistent weight gain resulting from damage to hypothalamic structures. aHO is associated with substantial morbidity, increased mortality, and marked impairment in quality of life. Etiologies include craniopharyngioma and other space-occupying lesions of the sellar/parasellar region, neurosurgical procedures, cranial irradiation, and traumatic brain injury. A multidisciplinary panel comprising ten specialists in neuroendocrinology, neurooncology, and neurosurgery from Germany, Austria, and Switzerland convened in Frankfurt am Main, Germany, on November 10, 2025, to discuss contemporary challenges and advances in this field. aHO should be conceptualized and treated within the broader clinical entity of hypothalamic syndrome, a complex disorder involving multiple neuroendocrine deficiencies, disturbances of circadian regulation, impaired control of hunger, satiety, and thirst, altered thermoregulation, and a range of cognitive, sleep-related, and psychosocial dysfunctions. Long-term outcomes for affected individuals are frequently unfavorable, largely due to increased risks of metabolic syndrome, cardiovascular disease, profound reductions in health-related quality of life, and elevated rates of premature mortality. The management of hypothalamic syndrome remains particularly challenging. Pharmacological strategies, including dextroamphetamine and glucagon-like peptide-1 receptor agonists, have demonstrated potential benefits for weight and hyperphagia-related outcomes. Recently, preliminary findings from a prospective, randomized, placebo-controlled clinical trial (TRANSCEND) provided encouraging evidence for the efficacy of setmelanotide, a melanocortin-4 receptor agonist. This perspectives report reviews clinical advances in epidemiology, diagnostics, treatment, and follow-up of patients with aHO and outlines key directions for future research aimed at improving outcomes in this vulnerable population.