Skip to main content

Advertisement

SpringerLink
Log in

Evidence of altered cortisol metabolism in critically ill patients: a prospective study

  • Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Context

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.

Objective

To investigate cortisol metabolism in critically ill patients utilising plasma cortisol: cortisone ratio as an index of 11β-HSD activity.

Setting

Tertiary level intensive care unit.

Patients

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.

Conclusions

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Bouachour G, Tirot P, Gouello JP, Mathieu E, Vincent JF, Alquier P (1995) Adrenocortical function during septic shock. Intensive Care Med 21:57–62

    Article  PubMed  CAS  Google Scholar 

  2. Hinshaw LB, Beller BK, Chang AC, Murray CK, Flournoy DJ, Passey RB, Archer LT (1985) Corticosteroid/antibiotic treatment of adrenalectomized dogs challenged with lethal E. coli. Circ Shock 16:265–277

    PubMed  CAS  Google Scholar 

  3. Venkatesh B, Mortimer RH, Couchman B, Hall J (2005) Evaluation of random plasma cortisol and the low dose corticotropin test as indicators of adrenal secretory capacity in critically ill patients: a prospective study. Anaesth Intensive Care 33:201–209

    PubMed  CAS  Google Scholar 

  4. Schein RM, Sprung CL, Marcial E, Napolitano L, Chernow B (1990) Plasma cortisol levels in patients with septic shock. Crit Care Med 18:259–263

    Article  PubMed  CAS  Google Scholar 

  5. Annane D, Sebille V, Troche G, Raphael JC, Gajdos P, Bellissant E (2000) A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. J Am Med Assoc 283:1038–1045

    Article  CAS  Google Scholar 

  6. Aygen B, Inan M, Doganay M, Kelestimur F (1997) Adrenal functions in patients with sepsis. Exp Clin Endocrinol Diabetes 105:182–186

    PubMed  CAS  Google Scholar 

  7. Barquist E, Kirton O (1997). Adrenal insufficiency in the surgical intensive care unit patient. J Trauma 42:27–31

    Article  PubMed  CAS  Google Scholar 

  8. Marik PE, Zaloga GP (2002) Adrenal insufficiency in the critically ill: a new look at an old problem. Chest 122:1784–1796

    Article  PubMed  Google Scholar 

  9. Rothwell PM, Udwadia ZF, Lawler PG (1991) Cortisol response to corticotropin and survival in septic shock. Lancet 337:582–583

    Article  PubMed  CAS  Google Scholar 

  10. Sibbald WJ, Short A, Cohen MP, Wilson RF (1977) Variations in adrenocortical responsiveness during severe bacterial infections. Unrecognized adrenocortical insufficiency in severe bacterial infections. Ann Surg 186:29–33

    Article  PubMed  CAS  Google Scholar 

  11. Yildiz O, Doganay M, Aygen B, Guven M, Keleutimur F, Tutuu A (2002). Physiological-dose steroid therapy in sepsis [ISRCTN36253388]. Crit Care 6:251–259

    Article  PubMed  Google Scholar 

  12. Marik PE, Zaloga GP (2003) Adrenal insufficiency during septic shock. Crit Care Med 31:141–145

    Article  PubMed  CAS  Google Scholar 

  13. Dickstein G, Shechner C, Nicholson WE, Rosner I, Shen-Orr Z, Adawi F, Lahav M (1991). Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. J Clin Endocrinol Metab 72:773–778

    Article  PubMed  CAS  Google Scholar 

  14. Cohen J, Venkatesh B, Galligan J, Thomas P (2004) Salivary cortisol concentration in the intensive care population: correlation with plasma cortisol values. Anaesth Intensive Care 32:843–845

    PubMed  CAS  Google Scholar 

  15. Hamrahian AH, Oseni TS, Arafah BM (2004). Measurements of serum free cortisol in critically ill patients. N Engl J Med 350:1629–1638

    Article  PubMed  CAS  Google Scholar 

  16. Ho JT, Al-Musalhi H, Chapman MJ, Quach T, Thomas PD, Bagley CJ, Lewis JG, Torpy DJ (2006). Septic shock and sepsis: a comparison of total and free plasma cortisol levels. J Clin Endocrinol Metab 91:105–114

    Article  PubMed  CAS  Google Scholar 

  17. Tomlinson JW, Stewart PM (2001) Cortisol metabolism and the role of 11β-hydroxysteroid dehydrogenase. Best Pract Res Clin Endocrinol Metab 15:61–78

    Article  PubMed  CAS  Google Scholar 

  18. Walker EA, Stewart PM (2003). 11β-hydroxysteroid dehydrogenase: unexpected connections. Trends Endocrinol Metab 14:334–339

    Article  PubMed  CAS  Google Scholar 

  19. Morita H, Isomura Y, Mune T, Daido H, Takami R, Yamakita N, Ishizuka T, Takeda N, Yasuda K, Gomez-Sanchez CE (2004) Plasma cortisol and cortisone concentrations in normal subjects and patients with adrenocortical disorders. Metabolism 53:89–94

    Article  PubMed  CAS  Google Scholar 

  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 43:1397–1407

    PubMed  CAS  Google Scholar 

  21. Quinkler M, Zehnder D, Lepenies J, Petrelli MD, Moore JS, Hughes SV, Cockwell P, Hewison M, Stewart PM (2005) Expression of renal 11β-hydroxysteroid dehydrogenase type 2 is decreased in patients with impaired renal function. Eur J Endocrinol 153:291–299

    Article  PubMed  CAS  Google Scholar 

  22. Duclos M, Marquez Pereira P, Barat P, Gatta B, Roger P (2005) Increased cortisol bioavailability, abdominal obesity, and the metabolic syndrome in obese women. Obes Res 13:1157–1166

    Article  PubMed  CAS  Google 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 18:1091–1098

    Article  PubMed  CAS  Google Scholar 

  24. McWhinney BC, Ward G, Hickman PE (1996) Improved HPLC method for simultaneous analysis of cortisol, 11-deoxycortisol, prednisolone, methylprednisolone, and dexamethasone in serum and urine. Clin Chem 42:979–981

    PubMed  CAS  Google Scholar 

  25. Kushnir MM, Neilson R, Roberts WL, Rockwood AL (2004) Cortisol and cortisone analysis in serum and plasma by atmospheric pressure photoionization tandem mass spectrometry. Clin Biochem 37:357–362

    Article  PubMed  CAS  Google Scholar 

  26. Strieter RM, Kunkel SL, Bone RC (1993) Role of tumor necrosis factor-alpha in disease states and inflammation. Crit Care Med 21:S447–S463

    Article  PubMed  CAS  Google 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 16:1037–1044

    Article  PubMed  CAS  Google Scholar 

  28. Heiniger CD, Rochat MK, Frey FJ, Frey BM (2001) TNF-alpha enhances intracellular glucocorticoid availability. FEBS Lett 507:351–356

    Article  PubMed  CAS  Google Scholar 

  29. Cai TQ, Wong B, Mundt SS, Thieringer R, Wright SD, Hermanowski-Vosatka A (2001) Induction of 11β-hydroxysteroid dehydrogenase type 1 but not-2 in human aortic smooth muscle cells by inflammatory stimuli. J Steroid Biochem Mol Biol 77:117–122

    Article  PubMed  CAS  Google Scholar 

  30. Suzuki S, Tsubochi H, Ishibashi H, Matsuda Y, Suzuki T, Krozowski ZS, Sasano H, Kondo T (2005) Inflammatory mediators down-regulate 11β-hydroxysteroid dehydrogenase type 2 in a human lung epithelial cell line BEAS-2B and the rat lung. Tohoku J Exp Med 207:293–301

    Article  PubMed  CAS  Google Scholar 

  31. Tomlinson JW, Moore J, Cooper MS, Bujalska I, Shahmanesh M, Burt C, Strain A, Hewison M, Stewart PM (2001) Regulation of expression of 11β-hydroxysteroid dehydrogenase type 1 in adipose tissue: tissue-specific induction by cytokines. Endocrinology 142:1982–1989

    Article  PubMed  CAS  Google Scholar 

  32. Vogeser M, Zachoval R, Felbinger TW, Jacob K (2002) Increased ratio of serum cortisol to cortisone in acute-phase response. Hormone Res 58:172–175

    Article  PubMed  CAS  Google Scholar 

  33. Vogeser M, Groetzner J, Kupper C, Briegel J (2003) The serum cortisol:cortisone ratio in the postoperative acute-phase response. Hormone Res 59:293–296

    Article  PubMed  CAS  Google Scholar 

  34. Hobson KG, Havel PJ, McMurtry AL, Lawless MB, Palmieri TL, Greenhalgh DD (2004) Circulating leptin and cortisol after burn injury: loss of diurnal pattern. J Burn Care Rehabil 25:491–499

    Article  PubMed  Google Scholar 

  35. Draper N, Stewart PM (2005) 11β-hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action. J Endocrinol 186:251–271

    Article  PubMed  CAS  Google Scholar 

  36. Bernier J, Jobin N, Emptoz-Bonneton A, Pugeat MM, Garrel DR (1998) Decreased corticosteroid-binding globulin in burn patients: relationship with interleukin-6 and fat in nutritional support. Crit Care Med 26:452–460

    Article  PubMed  CAS  Google Scholar 

  37. Hewitt KN, Walker EA, Stewart PM (2005) Minireview: hexose-6-phosphate dehydrogenase and redox control of 11β-hydroxysteroid dehydrogenase type 1 activity. Endocrinology 146:2539–2543

    Article  PubMed  CAS  Google Scholar 

  38. Victor VM, Rocha M, Fuente M de la (2004) Immune cells: free radicals and antioxidants in sepsis. Int Immunopharmacol 4:327–347

    Article  PubMed  CAS  Google Scholar 

  39. Ritter C, Andrades M, Guerreiro M, Zavaschi L, Gelain DP, Souza LF, Ribeiro CA, Clausell N, Menna-Barreto S, Moreira JC, Dal-Pizzol F (2003) Plasma oxidative parameters and mortality in patients with severe burn injury. Intensive Care Med 29:1380–1383

    Article  PubMed  Google Scholar 

  40. Rauz S, Walker EA, Shackleton CH, Hewison M, Murray PI, Stewart PM (2001) Expression and putative role of 11β-hydroxysteroid dehydrogenase isozymes within the human eye. Invest Ophthalmol Vis Sci 42:2037–2042

    PubMed  CAS  Google 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]

  42. Bollaert PE, Charpentier C, Levy B, Debouverie M, Audibert G, Larcan A (1998) Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med 26:645–650

    Article  PubMed  CAS  Google Scholar 

  43. van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345:1359–1367

    Article  PubMed  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 94:14924–14929

    Article  PubMed  CAS  Google Scholar 

  45. Nomura S, Fujitaka M, Sakura N, Ueda K (1997) Circadian rhythms in plasma cortisone and cortisol and the cortisone/cortisol ratio. Clin Chim Acta 266:83–91

    Article  PubMed  CAS  Google Scholar 

  46. Jerjes WK, Cleare AJ, Wessely S, Wood PJ, Taylor NF (2005) Diurnal patterns of salivary cortisol and cortisone output in chronic fatigue syndrome. J Affect Disord 87:299–304

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the Princess Alexandra Hospital Research Foundation and Australia and New Zealand College of Anaesthetists.

Author information

Authors and Affiliations

  1. Department of Intensive Care, Princess Alexandra and Wesley Hospitals, University of Queensland, 4102, Queensland, Australia

    Bala Venkatesh

  2. Department of Intensive Care, Royal Brisbane Hospital, University of Queensland, Queensland, Australia

    Jeremy Cohen & Peter Thomas

  3. Department of Endocrinology, Princess Alexandra Hospital, University of Queensland, Queensland, Australia

    Ingrid Hickman, Janelle Nisbet, Gregory Ward & John Prins

  4. Division of Anesthesiology and Critical Care, University of Queensland, Queensland, Australia

    Jonathan Hall

Authors
  1. Bala Venkatesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeremy Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ingrid Hickman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Janelle Nisbet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gregory Ward
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jonathan Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. John Prins
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bala Venkatesh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Venkatesh, B., Cohen, J., Hickman, I. et al. Evidence of altered cortisol metabolism in critically ill patients: a prospective study. Intensive Care Med 33, 1746–1753 (2007). https://doi.org/10.1007/s00134-007-0727-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-007-0727-7

Keywords

Search

Navigation