Serial changes in plasma total cortisol, plasma free cortisol and tissue cortisol activity in patients with septic shock: An observational study

Cohen, Jeremy, Lassig Smith, Melissa, Deans, Renae V., Pretorius, Carel J., Ungerer, Jacobus P. J., Tan, Terrence, Jones, Mark and Venkatesh, Bala (2012) Serial changes in plasma total cortisol, plasma free cortisol and tissue cortisol activity in patients with septic shock: An observational study. Shock, 37 1: 28-33. doi:10.1097/SHK.0b013e318239b809

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Author Cohen, Jeremy
Lassig Smith, Melissa
Deans, Renae V.
Pretorius, Carel J.
Ungerer, Jacobus P. J.
Tan, Terrence
Jones, Mark
Venkatesh, Bala
Title Serial changes in plasma total cortisol, plasma free cortisol and tissue cortisol activity in patients with septic shock: An observational study
Journal name Shock   Check publisher's open access policy
ISSN 1073-2322
1540-0514
Publication date 2012-01-01
Year available 2011
Sub-type Article (original research)
DOI 10.1097/SHK.0b013e318239b809
Open Access Status Not yet assessed
Volume 37
Issue 1
Start page 28
End page 33
Total pages 6
Place of publication Baltimore, MD, United States
Publisher Lippincott Williams & Wilkins
Language eng
Subject 2711 Emergency Medicine
2706 Critical Care and Intensive Care Medicine
Abstract Published data on adrenocortical function in septic shock have enrolled patients at various stages of critical illness and predominantly used plasma total cortisol, with minimal information on serial changes. Moreover, plasma free cortisol and tissue corticosteroid activity may not be strongly associated; however, few published data exist. The aim of this prospective observational study was to investigate serial changes in plasma total and free cortisol and tissue cortisol activity in septic shock. Twenty-nine adult patients admitted with septic shock to a tertiary-level intensive care unit were enrolled. A low-dose corticotropin test was performed on day 1. Plasma total and free cortisol, cortisone, transcortin, and urinary free cortisol and cortisone were analyzed on days 1 to 5, 7, and 10. Urinary and plasma cortisol-cortisone ratios (F:E ratio) were calculated as indices of 11-β hydroxysteroid dehydrogenase 2 and global 11-β hydroxysteroid dehydrogenase activity, respectively. Baseline total and free plasma cortisol values from 10 healthy control subjects were obtained for comparative analysis. Baseline plasma total and free cortisol levels were significantly higher than controls (457.8 ± 193 vs. 252 ± 66 nmol/L, P = 0.0002; and 50.83 ± 43.19 vs. 6.4 ± 3.2, P < 0.0001, respectively). Plasma free cortisol rose proportionately higher than total cortisol (124% ± 217.3% vs. 40% ± 33.2%, P = 0.007) following corticotropin. Baseline plasma and urinary F:E ratios were elevated over the reference ranges (13.13 ± 1.5, 1.69 ± 2.8) and were not correlated with plasma free cortisol values (r = 0.2, 0.3 respectively). Over the study period, total cortisol levels and plasma F:E ratios remained elevated, whereas plasma free cortisol levels and urinary F:E ratio declined. At baseline, plasma free cortisol levels were higher in patients who subsequently survived (23.7 ± 10.5 vs. 57.9 ± 45.8 nmol/L, P = 0.04). In septic shock, there is a differential response of plasma total and free cortisol over time and in response to corticotropin. Changes in plasma and urinary F:E ratios suggest tissue modulation of 11-β hydroxysteroid dehydrogenase activity. Total plasma cortisol measurements may not reflect the global adrenal response in septic shock. ABBREVIATIONS: 11β-HSD-11β- hydroxysteroid dehydrogenaseAPACHE-Acute Physiology and Chronic Health EvaluationCBG-corticosteroid-binding globulinFC-free plasma cortisolF:E ratio-cortisol-cortisone ratioSOFA-Sequential Organ Failure Assessment.
Formatted abstract
Introduction: Published data on adrenocortical function in septic shock have enrolled patients at various stages of critical illness and predominantly used plasma total cortisol, with minimal information on serial changes. Moreover plasma free cortisol and tissue corticosteroid activity may not be strongly associated; however little published data exist .The aim of this prospective observational study was to investigate serial changes in plasma total and free cortisol, and tissue cortisol activity in septic shock.

Methods: Twenty-nine adult patients admitted with septic shock to a tertiary level intensive care unit were enrolled. A low dose corticotrophin test was performed on day 1. Plasma total and free cortisol, cortisone, transcortin and urinary free cortisol and cortisone were analysed on days 1-5, 7 and 10. Urinary and plasma cortisol: cortisone ratios (F:E ratio) were calculated as indices of 11-ß Hydroxysteroid dehydrogenase 2 and global 11-ß Hydroxysteroid dehydrogenase activity respectively. Baseline total and free plasma cortisol values from ten healthy control subjects were obtained for comparative analysis.

Results
: Baseline plasma total and free cortisol levels were significantly higher than controls (457.8±193 vs. 252±66nmol/l, p=0.0002 and 50.83±43.19 vs. 6.4±3.2, p<0.0001 respectively). Plasma free cortisol rose proportionately higher than total cortisol (124±217.3% vs. 40±33.2%, p=0.007) following corticotrophin. Baseline plasma and urinary F:E ratios were elevated over the normal ranges (13.13±1.5, 1.69±2.8) and were not correlated with plasma free cortisol values (r=0.2, 0.3 respectively). Over the study period, total cortisol levels and plasma F:E ratios remained elevated while plasma free cortisol levels and urinary F:E ratio declined. At baseline, plasma free cortisol levels were higher in patients who subsequently survived (23.7±10.5 vs. 57.9±45.8 nmol/l, p=0.04).

Conclusions
: In septic shock there is a differential response of plasma total and free cortisol over time and in response to corticotrophin. Changes in plasma and urinary F:E ratios suggest tissue modulation of 11-ß hydroxysteroid dehydrogenase activity. Total plasma cortisol measurements may not reflect the global adrenal response in septic shock.
Keyword 11β-hydroxysteroid dehydrogenase
adrenal function
Cortisol
mass spectrometry
septic shock
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article in press. Available online September 2011.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
 
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Created: Thu, 20 Oct 2011, 19:44:15 EST by Dr Jeremy Cohen on behalf of Anaesthesiology and Critical Care - RBWH