Hypothalamic syndrome and acquired hypothalamic obesity: from fragmented care to integrated multidisciplinary management.

Acquired hypothalamic obesity (AHO) is a complex neuroendocrine disorder characterized by rapid weight gain and multisystem dysfunction following hypothalamic damage. AHO represents the weight-related manifestation of the broader hypothalamic syndrome (HS), a heterogeneous spectrum of dysfunctions that can also encompass disturbances in pituitary function, energy expenditure, sleep, behavior, and thermoregulation, with obesity itself absent in some affected individuals. This narrative review provides an updated and integrative overview of AHO pathophysiology, clinical characterization, and current and emerging approaches to diagnosis, prevention, and treatment, with the aim of proposing a multidimensional framework to improve patient care. The literature, including seminal studies, recent systematic reviews, clinical trials, and expert consensus statements, was critically appraised with emphasis on clinical applicability and existing knowledge gaps. Current evidence highlights the limitations of BMI-based assessment and supports a multidomain clinical approach. In this context, a three-layer diagnostic model is proposed, integrating etiological factors, longitudinal anthropometric and metabolic assessment, and domain-specific clinical evaluation. Preventive strategies remain underexplored, although hypothalamus-sparing interventions, early monitoring of weight trajectory, and management in specialized Pituitary Tumor Centers of Excellence in surgical cases appear critical. Therapeutic options are limited, with modest evidence for conventional treatments; however, emerging therapies targeting the melanocortin pathway, including MC4R agonists, showed promising results. Overall, AHO requires a paradigm shift toward early identification, multidimensional assessment, and coordinated multidisciplinary care, with future research prioritizing preventive strategies and robust clinical trials to improve outcomes.