Endocrine Abstracts

Background: Advancements in medical care have significantly improved survival after major traumatic injury and the main risks are now sepsis and multi-organ failure. An understanding of the hormonal, inflammatory and metabolic changes that occur following trauma is still evolving but it is clear that they impact significantly upon patient prognosis. To date, studies that have examined trauma-induced changes in steroid metabolism have analysed samples taken from patients post-hospital admission, culminating in marked variability in the time of first blood sample. Here we investigated the major changes in steroidogenesis following trauma, focusing on the immediate time after injury.

Methods and Results: We recruited 31 male trauma patients (mean age 28.1 years range 19–59) who had an initial blood sample taken within 1-hour of injury, with subsequent samples taken 4–12 and 48–72 h post-injury. Our control cohort was 35 healthy male volunteers (mean 30 years; range 18–50). Sixteen serum steroids were quantified by liquid chromatography tandem mass spectrometry using a Waters Acquity UPLC and a Xevo-XS mass spectrometer;

• precursors; progesterone, 17hydroxyprogesterone,

• glucocorticoids; 11-deoxycortisol, cortisol, cortisone,

• mineralocorticoids; 11-deoxycortocosterone, corticosterone,

• androgen precursors; DHEAS, DHEA, androstenedione,

• androgens; testosterone, DHT,

• 11-oxygenated androgens; 11-hydroxy-androstenedione, 11hydroxy-testosterone, 11keto-androstenedione and 11keto-testosterone.

Eleven of the sixteen steroids were significantly increased 1 h after injury in comparison to healthy controls. Maximum concentrations of these steroids were observed one hour post injury, concentrations then decreased at 4–12 h and reached levels similar (or lower than) healthy controls 48–72 h after injury. The exceptions were cortisone, 11Keto-androstenedione, 11Keto-testosterone, testosterone and DHT. The concentrations of testosterone and DHT decreased one hour post injury when compared to healthy controls, then decreased further at 4–12 and again at 48–72 h post injury. To estimate when trauma-induced steroid metabolism changes occurred we employed generalised additive models (GAMs) to the samples collected within the first hour of injury. GAMs allowed us to estimate the time excretion of each steroid was altered compared to the healthy controls. The modelling estimated injury-induced changes in steroid precursors 9 min post trauma then in a sequential manner reflecting steroidogenesis to active androgens at 35 min, demonstrating rapid disruption of both adrenal and gonadal steroid biosynthesis.

Conclusions: These data show major changes in steroidogenesis following trauma, for the first time focusing on the immediate time after injury. Whether those patients that have ultra-early changes in steroid metabolism are associated with poor patient outcome warrants further investigation.