Epidemiology of acquired hypothalamic obesity following traumatic brain injury and nonspecific hypothalamic microinjury: A nationwide German claims data analysis

Acquired hypothalamic obesity (aHO) is characterized by rapid and persistent weight gain resulting from structural or functional damage to the hypothalamus, typically accompanied by neuroendocrine dysfunction. While aHO is well described in the context of hypothalamic or suprasellar tumors, particularly craniopharyngioma, little is known about its epidemiology in non-tumor-related etiologies such as traumatic brain injury (TBI) or subtle, unrecognized hypothalamic injuries. This study estimates the incidence and clinical characteristics of aHO in patients with traumatic brain injury (TBI-aHO) and hypothalamic-pituitary axis dysfunction of unclear origin, referred to as unspecified microinjury (UM-aHO). We conducted a retrospective cohort study using German statutory health insurance claims data (N = 6.3 million, 2010-2022). Patients were included based on either an incident diagnosis of TBI or a diagnostic algorithm indicating hypothalamic-pituitary axis dysfunction without a documented causal event. aHO was defined via incident obesity coding and validated by concomitant arginine vasopressin deficiency (AVP-D) and desmopressin prescription. For UM-aHO, additional validation required at least three concurrent neuroendocrine replacement therapies. Sensitivity analyses assessed the robustness of case definitions. The estimated incidence of TBI-aHO was 1.78 per million persons (mean age: 42 years; 27% female), corresponding to approximately 520 prevalent cases in Germany. UM-aHO showed a slightly higher incidence of 2.12 per million (mean age: 37 years; 55% female), with an estimated 660 prevalent cases. Following the diagnosis of incident obesity, most patients in both cohorts received at least two neuroendocrine therapies in addition to desmopressin, most commonly including hydrocortisone and levothyroxine sodium. This is the first population-based study to characterize aHO following non-tumor-related hypothalamic injury. Both TBI and subtle, nonspecific hypothalamic microinjuries contribute meaningfully to the burden of aHO in clinical practice. These findings underscore the need for increased clinical awareness and early recognition of hypothalamic dysfunction in patients beyond classical tumor etiologies.