Evidence of altered cortisol metabolism in critically ill patients: a prospective study
- 243 Downloads
Changes in cortisol metabolism due to altered activity of the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) have been implicated in the pathogenesis of hypertension, obesity and the metabolic syndrome. No published data exist on the activity of this enzyme in critical illness.
To investigate cortisol metabolism in critically ill patients utilising plasma cortisol: cortisone ratio as an index of 11β-HSD activity.
Tertiary level intensive care unit.
Three cohorts of critically ill patients: sepsis (n = 13); multitrauma (n = 20); and burns (n = 19).
Main outcome measures
Serial plasma cortisol: cortisone ratios.
Measurements and main results
Plasma total cortisol cortisone ratios were determined serially after admission to the intensive care unit. As compared with controls, the plasma cortisol:cortisone ratio was significantly elevated in the sepsis and trauma cohorts on day 1 (22 ± 9, p = 0.01, and 23 ± 19, p = 0.0003, respectively) and remained elevated over the study period. Such a relationship was not demonstrable in burns. The ratio was significantly correlated with APACHE II (r = 0.77, p = 0.0008) and Simplified Acute Physiology Score (r = 0.7, p = 0.003) only on day 7 and only in the burns cohort. There were no significant correlations observed between total plasma cortisol or cortisone and sickness severity in the sepsis and trauma cohorts.
In critically ill patients, there is evidence of altered cortisol metabolism due to an increase in 11β-HSD activity as demonstrated by an elevation of plasma cortisol: cortisone ratios. Further studies with larger sample sizes specifically designed to examine altered tissue 11β-HSD activity and its clinical significance and correlation with outcome are warranted.
Keywords11β-hydroxysteroid dehydrogenase Septic shock Trauma Burns Critical illness Cortisol–cortisone ratios
- 20.Morineau G, Boudi A, Barka A, Gourmelen M, Degeilh F, Hardy N, al-Halnak A, Soliman H, Gosling JP, Julien R, Brerault JL, Boudou P, Aubert P, Villette JM, Pruna A, Galons H, Fiet J (1997) Radioimmunoassay of cortisone in serum, urine, and saliva to assess the status of the cortisol-cortisone shuttle. Clin Chem 43:1397–1407PubMedGoogle Scholar
- 23.Mariniello B, Ronconi V, Sardu C, Pagliericcio A, Galletti F, Strazzullo P, Palermo M, Boscaro M, Stewart PM, Mantero F, Giacchetti G (2005). Analysis of the 11β-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) in human essential hypertension. Am J Hypertens 18:1091–1098PubMedCrossRefGoogle Scholar
- 27.Cooper MS, Bujalska I, Rabbitt E, Walker EA, Bland R, Sheppard MC, Hewison M, Stewart PM (2001) Modulation of 11β-hydroxysteroid dehydrogenase isozymes by proinflammatory cytokines in osteoblasts: an autocrine switch from glucocorticoid inactivation to activation. J Bone Miner Res 16:1037–1044PubMedCrossRefGoogle Scholar
- 41.Tomlinson JW, Sherlock M, Hughes B, Hughes SV, Kilvington F, Bartlett W, Courtney R, Rejto P, Carley W, Stewart PM (2007) Inhibition of 11β-HSD1 activity in vivo limits glucocorticoid exposure to human adipose tissue and decreases lipolysis. J Clin Endocrinol Metab 2007 [Epub ahead of print]Google Scholar
- 44.Kotelevtsev Y, Holmes MC, Burchell A, Houston PM, Schmoll D, Jamieson P, Best R, Brown R, Edwards CR, Seckl JR, Mullins JJ (1997) 11β-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress. Proc Natl Acad Sci USA 94:14924–14929PubMedCrossRefGoogle Scholar