Acute Endocrine Alterations After Traumatic Brain Injury and 6‐Month Functional Outcome

OBJECTIVE: Acute multi-axis endocrine alterations after traumatic brain injury (TBI) remain incompletely characterized. This study aimed to examine their temporal patterns and explore their associations with 6-month functional outcome and early inflammatory markers. METHODS: We conducted a single-center prospective observational cohort study of hospitalized adults with traumatic brain injury. Among 130 enrolled patients, 125 with complete 6-month Glasgow Outcome Scale-Extended follow-up were included. Blood samples were collected on Day 1, 7, and 14 after injury to assess hypothalamic-pituitary-adrenal, thyroid, gonadal, and growth hormone axes. Day-1 inflammatory markers were measured. Associations of individual biomarkers with unfavorable 6-month outcome were evaluated using separate Firth penalized logistic regression models adjusted for admission Glasgow Coma Scale (GCS). RESULTS: Serum cortisol levels at 08:00 and 16:00 decreased significantly over time (Kendall's W = 0.205 [95% CI 0.085-0.388] and 0.239 [95% CI 0.126-0.408], respectively; both p < 0.001), whereas triiodothyronine, free triiodothyronine, and thyroid-stimulating hormone increased during the acute phase. Patients with unfavorable 6-month outcome had higher day-1 interleukin-6, neutrophil count, and procalcitonin levels and lower day-1 triiodothyronine and free triiodothyronine levels than those with favorable outcome. After adjustment for admission GCS in separate Firth models, interleukin-6, white blood cell count, neutrophil count, procalcitonin, day-1 triiodothyronine, and day-1 free triiodothyronine were not significantly associated with unfavorable 6-month outcome. INTERPRETATION: Endocrine alterations after acute TBI were heterogeneous across injury severity groups and time points. Although selected day-1 inflammatory and thyroid-axis measures differed between outcome groups, their associations with unfavorable 6-month functional outcome were not statistically significant after adjustment for admission GCS. These outcome-related findings require validation in larger cohorts.