OBJECTIVE Despite the prevalence of frontal injury following traumatic brain injury (TBI) in adults and children with potentially concomitant hypothalamic and pituitary involvement, endocrine dysfunction acutely following TBI has not been well studied in children. METHODS To study the acute pediatric endocrine response after severe TBI (Glasgow Coma Scale <or= 8), an endocrine panel, including cortisol, ACTH, TSH, T3, T4, free T4, GH, and prolactin levels, were obtained in 37 children (1-17 years) on the day of injury and post-injury days (PID) 3 and 7. Outcome was determined at 6-month follow-up using the Glasgow Outcome Score (GOS) extended modified for pediatric patients (GOS-E Peds) to compare "good" (GOS-E Peds 1-2) to "poor" (GOS-E Peds 3-5) outcomes. RESULTS Our results showed that following severe TBI in children, cortisol was significantly elevated (24.46 +/- 13.41 microg/dL) on PID 1 along with ACTH but then returned to normal (10.14-19.92 microg/dL) by PID 3; 46% and 14% of children had a low cortisol and ACTH (<10.14 and <2, respectively) in the acute period. CONCLUSIONS In summary, the cortisol response to trauma and stress in the acute period following severe TBI in the majority of children was altered, though seemingly appropriate cortisol was abnormally low in a significant percentage of children. Further study as to the significance of these findings is needed, but this study provides preliminary insight into the potential impact of severe TBI on the acute response of the hypothalamic-pituitary axis in children.