OR21-3 The Endocrine-Immune Response to Severe Trauma

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR21-HPA Axis: New Clinical Developments
Clinical
Sunday, June 16, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 11:45 AM
Room 134 (Moscone Center)
Mark Foster*1, Neil Hill2, Abigail A Routledge3, Conor Bentley4, Donna M O'Neil5, Julian F Bion6, Mark M Midwinter7, Joanne L Fallowfield8 and Janet M Lord5
1University Hospital Birmingham, Birmingham, United Kingdom, 2Imperial College London, London, United Kingdom, 3University Hospital Birmingha, Birmingham, United Kingdom, 4University Hospital Birmingham, BIRMINGHAM, United Kingdom, 5University of Birmingham, Birmingham, United Kingdom, 6University of Birmingham, BIRMIRGHAM, United Kingdom, 7University Hospital Birmingha, BIRMINGHAM, United Kingdom, 8Institute of Naval Medicine, Alverstoke, United Kingdom
In 2011, there were 1.21 million deaths from Road Traffic Accidents[i] worldwide  In Afghanistan over 10 years there have been 2005 battle injuries.[ii]  Recent advances in military Trauma Care have improved survival of the more severely injured  whose rehabilitation pathway is profoundly influenced by  their inflammatory, hormonal and metabolic response to trauma.  Cortisol/DHEA ratios have been shown to relate to immune function in the elderly.[iii]

102 severely injured patients (52 military, 50 civilian; mean Injury Severity Score 31 (4-75)) entered a prospective study to characterise the immune, inflammatory and endocrine response to trauma.  Blood and 24 hour urine samples were obtained at 24 hours and at 3, 5, 10, 14, 21, 28 days and 2, 3, 4 and 6 months post injury.  Muscle thickness (ultrasound) was measured weekly and at 3, 4, 5 and 6 months. 

Results: The cortisol:cortisone (F:E) ratio peaked at 15 days, returning to normal after 2 months.  Initial DHEA concentrations post injury were lower than healthy controls (p<0.0001), but began to normalise by 4 months.  DHEA-Sulphate (DHEAS) concentrations had still not returned to normal by 6 months post injury.  The cortisol:DHEAS ratio peaked at 20 days and normalised by 6 months.  Initial testosterone concentrations were low (p<0.0001), correlated with DHEAS and DHEA (p<0.0001), and normalised  by 3 months.  Testosterone and F:E ratio (p<0.0001) correlated with nitrogen excretion, which  peaked early at 23 gN.day-1 and dropped below 10 gN.day-1 by week 6.  Muscle thickness diminished, plateaued and recovered in phase with nitrogen excretion (p<0.0001).  Muscle thickness reduced by  31%  at 6 weeks, recovering by 5 months.

The Cortisol/DHEA imbalance was temporally associated with a catabolic state in severe trauma.  Anabolic hormone recovery reversed catabolism and was strongly associated with testosterone levels.   We postulate that  anabolic hormones and  DHEA could have a therapeutic role in mitigating the catabolic response to severe trauma.

[i] WHO- Causes of Death.  http://www.who.int/mediacentre/factsheets/fs310/en/index.html Taken 12/10/2012.[ii] DASA Report - http://www.mod.uk/NR/rdonlyres/8C466769-0672-4970-A5C7-EDECC2057859/0/casualties_afghanistan _upto_31Aug12.pdf Taken 12/10/2012.[iii] Stephen K Butcher et al., “Raised Cortisol:DHEAS Ratios in the Elderly After Injury: Potential Impact Upon Neutrophil Function and Immunity,” Aging Cell 4, no. 6 (December 1, 2005): 319–324.

Nothing to Disclose: MF, NH, AAR, CB, DMO, JFB, MMM, JLF, JML

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Surgical Reconstruction and Microbilogy Research Centre, Royal Centre for Defence Medicine, Royal College of Surgeons of England Research Fellowship Award, Drummond Foundation