The ultra-acute steroid response to traumatic injury: a cohort study

Author:

Bentley Conor123,Hazeldine Jon12ORCID,Bravo Laura4,Taylor Angela E5,Gilligan Lorna C5,Shaheen Fozia5,Acharjee Animesh246ORCID,Gkoutos George2467,Foster Mark A128,Arlt Wiebke59ORCID,Lord Janet M129

Affiliation:

1. Institute of Inflammation and Ageing, University of Birmingham , Birmingham B15 2TT , United Kingdom

2. National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham , Birmingham B15 2TT , United Kingdom

3. School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham , Birmingham B15 2TT , United Kingdom

4. Institute of Cancer and Genomic Sciences, Centre for Computational Biology, University of Birmingham , Birmingham B15 2TT , United Kingdom

5. Institute of Metabolism and Systems Research, University of Birmingham , Birmingham B15 2TT , United Kingdom

6. Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust , Birmingham B15 2TT , United Kingdom

7. Medical Research Council Health Data Research UK (HDR) , United Kingdom

8. Royal Centre for Defence Medicine , Birmingham Research Park, Birmingham B15 2SQ , United Kingdom

9. National Institute for Health Research Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust , Birmingham B15 2GW , United Kingdom

Abstract

AbstractObjectiveTrauma-induced steroid changes have been studied post-hospital admission, resulting in a lack of understanding of the speed and extent of the immediate endocrine response to injury. The Golden Hour study was designed to capture the ultra-acute response to traumatic injury.DesignWe conducted an observational cohort study including adult male trauma patients <60 years, with blood samples drawn ≤1 h of major trauma by pre-hospital emergency responders.MethodsWe recruited 31 adult male trauma patients (mean age 28 [range 19-59] years) with a mean injury severity score (ISS) of 16 (IQR 10-21). The median time to first sample was 35 (range 14-56) min, with follow-up samples collected 4-12 and 48-72 h post-injury. Serum steroids in patients and age- and sex-matched healthy controls (HCs) (n = 34) were analysed by tandem mass spectrometry.ResultsWithin 1 h of injury, we observed an increase in glucocorticoid and adrenal androgen biosynthesis. Cortisol and 11-hydroxyandrostendione increased rapidly, whilst cortisone and 11-ketoandrostenedione decreased, reflective of increased cortisol and 11-oxygenated androgen precursor biosynthesis by 11β-hydroxylase and increased cortisol activation by 11β-hydroxysteroid dehydrogenase type 1. Active classic gonadal androgens testosterone and 5α-dihydrotestosterone decreased, whilst the active 11-oxygenated androgen 11-ketotestosterone maintained pre-injury levels.ConclusionsChanges in steroid biosynthesis and metabolism occur within minutes of traumatic injury. Studies that address whether ultra-early changes in steroid metabolism are associated with patient outcomes are now required.

Funder

National Institute for Health Research

University Hospitals Birmingham NHS Foundation Trust

University of Birmingham

Publisher

Oxford University Press (OUP)

Subject

Endocrinology,General Medicine,Endocrinology, Diabetes and Metabolism

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