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Adrenal-exhaustion syndrome in patients with liver disease

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Abstract

Objective

Adrenal failure is emerging as an important cause of excess morbidity and mortality in critically ill patients. We have recently reported the high incidence of adrenal failure in patients with liver disease, the so called “hepato-adrenal syndrome.” It has been noted that patients who on initial testing may have “normal” adrenal function subsequently progress to overt adrenal failure, the adrenal-exhaustion syndrome. The goal of this study was to further characterize this syndrome.

Design

Retrospective review of the “Hepatic Cortisol Research and Adrenal Pathophysiology Study” database.

Setting

Liver transplant ICU of a tertiary care university hospital.

Patients and methods

Patients who on initial testing had “normal” adrenal function were followed, and adrenal function testing was repeated in those who failed to improve. The patients were grouped as follows: (1) patients who developed adrenal failure on follow-up testing; and (2) patients who had normal adrenal function during their ICU stay. The incidence and risk factors for the development of adrenal-exhaustion syndrome were determined.

Measurements and results

The study cohort consisted of 221 patients, of whom 120 (54%) were diagnosed with adrenal insufficiency on initial diagnostic testing and were excluded from further analysis. The remaining 101 patients comprised those who made up the group of interest. On follow-up, 16 (16%) of these developed adrenal failure a mean of 3 days after initial testing. The only factor that predicted the development of adrenal-exhaustion syndrome was a low HDL level (p < 0.001).

Conclusion

This study demonstrates that adrenal failure is a dynamic process and that repeat adrenal function testing is indicated in patients who remain hemodynamically unstable or fail to improve with aggressive supportive treatment. Low HDL levels may be pathogenetically linked to the development of adrenal failure.

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References

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

    Article  PubMed  CAS  Google Scholar 

  2. Marik PE, Kiminyo K, Zaloga GP (2002) Adrenal insufficiency in critically ill HIV infected patients. Crit Care Med 30:1267–1273

    Article  PubMed  Google Scholar 

  3. Kilger E, Weis F, Briegel J, Frey L, Goetz AE, Reuter D, Nagy A, Schuetz A, Lamm P, Knoll A, Peter K (2003) Stress doses of hydrocortisone reduce severe systemic inflammatory response syndrome and improve early outcome in a risk group of patients after cardiac surgery. Crit Care Med 31:1068–1074

    Article  PubMed  CAS  Google Scholar 

  4. Dimopoulou I, Tsagarakis S, Kouyialia AT, Roussou P, Assithianakis ZG, Christoforaki M, Ilias I, Sakas DE, Thalassinos N, Roussos C (2004) Hypothalamic-pituitary-adrenal axis dysfunction in critically ill patients with traumatic brain injury: Incidence, pathophysiology and relationship to vasopressor dependence and peripheral interleukin-6 levels. Crit Care Med 32:404–408

    Article  PubMed  CAS  Google Scholar 

  5. Nacul FE, Jardim A, MacCord F, Penido C, Gomes MV (2002) Hemodynamic instability secondary to adrenal insufficiency in a major burn patient. Burns 28:270–272

    Article  PubMed  Google Scholar 

  6. Sheridan RL, Ryan CM, Tompkins RG (1993) Acute adrenal insufficiency in the burn intensive care unit. Burns 19:63–66

    Article  PubMed  CAS  Google Scholar 

  7. Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871

    Article  PubMed  CAS  Google Scholar 

  8. van Leeuwen HJ, Heezius EC, Dallinga GM, Van Strijp JA, Verhoef J, van Kessel KP (2003) Lipoprotein metabolism in patients with severe sepsis. Crit Care Med 31:1359–1366

    Article  PubMed  CAS  Google Scholar 

  9. Rasaratnam B, Kaye D, Jennings G, Dudley F, Chin-Dusting J (2003) The effect of selective intestinal decontamination on the hyperdynamic circulatory state in cirrhosis. A randomized trial. Ann Intern Med 139:186–193

    PubMed  Google Scholar 

  10. Mookerjee RP, Sen S, Davies NA, Hodges SJ, Williams R, Jalan R (2003) Tumour necrosis factor alpha is an important mediator of portal and systemic haemodynamic derangements in alcoholic hepatitis. Gut 52:1182–1187

    Article  PubMed  CAS  Google Scholar 

  11. Marik PE, Gayowski T, Starzl TE (2005) The hepato-adrenal syndrome: A common yet unrecognized condition. Crit Care Med 33:1254–1259

    Article  PubMed  Google Scholar 

  12. 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 

  13. Beishuizen A, Thijs LG, Vermes I (2002) Decreased levels of dehydroepiandrosterone sulphate in severe critical illness: a sign of exhausted adrenal reserve? Critical Care 6:434–438

    Article  PubMed  Google Scholar 

  14. Chien JY, Jerng JS, Yu CJ, Yang PC (2005) Low serum level of high-density lipoprotein cholesterol is a poor prognostic factor for severe sepsis. Crit Care Med 33:1688–1693

    Article  PubMed  CAS  Google Scholar 

  15. Marik PE (2006) Dyslipidemia in the critically ill. Crit Care Clin (in press)

  16. Marik PE (2004) Unraveling the mystery of adrenal failure in the critically ill. Crit Care Med 32:596–597

    Article  PubMed  Google Scholar 

  17. Cooper MD, Stewart PM (2003) Corticosteroid insufficiency in acutely ill patients. N Engl J Med 348:727–734

    Article  PubMed  CAS  Google Scholar 

  18. Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: A severity of disease classification system. Crit Care Med 13:818–828

    Article  PubMed  CAS  Google Scholar 

  19. Van der Voort PHJ, Koopman M (2004) Follow-up corticotropin stimulating tests during ICU stay. Intensive Care Med 30 [Suppl 1]:S61

  20. Beishuizen A, Vermes I, Hylkema BS, Haanen C (1999) Relative eosinophilia and functional adrenal insufficiency in critically ill patients [letter]. Lancet 353:1675–1676

    Article  PubMed  CAS  Google Scholar 

  21. Marik PE, Sprung CL, Annane D, Keh D, Meduri GU, Zaloga G, Singer M, Beishuizen A (2006) International Collaborative Task Force. The diagnosis and treatment of corticosteroid insufficiency in critically ill patients. Crit Care Med (in press)

  22. van der Voort PH, Gerritsen RT, Bakker AJ, Boerma EC, Kuiper MA, de Heide L (2003) HDL-cholesterol level and cortisol response to synacthen in critically ill patients. Intensive Care Med 29:2199–2203

    Article  PubMed  Google Scholar 

  23. Borkowski AJ, Levin S, Delcroix C, Mahler A, Verhas V (1967) Blood cholesterol and hydrocortisone production in man: quantitative aspects of the utilization of circulating cholesterol by the adrenals at rest and under adrenocorticotropin stimulation. J Clin Invest 46:797–811

    PubMed  CAS  Google Scholar 

  24. Yaguchi H, Tsutsumi K, Shimono K, Omura M, Sasano H, Nishikawa T (1998) Involvement of high-density lipoprotein as substrate cholesterol for steroidogenesis by bovine adrenal fasciculo-reticularis cells. Life Sci 62:1387–1395

    Article  PubMed  CAS  Google Scholar 

  25. Acton S, Rigotti A, Landschultz KT, Xu S, Hobbs HH, Krieger M (1996) Identification of scavenger receptor SR-BI as a high-density lipoprotein receptor. Science 271:518–520

    Article  PubMed  CAS  Google Scholar 

  26. Calco D, Gomez-Coronado D, Lasuncion MA, Vega MA (1997) CLA-I is an 85-kD plasma membrane glycoprotein that acts as a high-affinity receptor for both native (HDL, LDL, and VLDL) and modified (OxLDL and AcLDL) lipoproteins. Arterioscler Thromb Vasc Biol 17:2341–2349

    PubMed  Google Scholar 

  27. de la Llera-Moya M, Connelly MA, Drazul D, Klein SM, Favari E, Yancey PG, Williams DL, Rothblat GH (2001) Scavenger receptor class B type 1 affects cholesterol homeostasis by magnifying cholesterol flux between cells and HDL. J Lipid Res 42:1969–1978

    PubMed  Google Scholar 

  28. Liu J, Heikkila P, Meng QH, Kahri AI, Tikkanen MJ, Voutilainen R (2000) Expression of low- and high-density lipoprotein receptor genes in human adrenals. Eur J Endocrinol 142:677–682

    Article  PubMed  CAS  Google Scholar 

  29. Liu J, Voutilainen R, Heikkila P, Kahri AI (1997) Ribonucleic acid expression of the CLA-1 gene, a human homolog to mouse high-density lipoprotein receptor SR-BI, in human adrenal tumors and cultured adrenal cells. J Clin Endocrinol Metab 82:2522–2527

    Article  PubMed  CAS  Google Scholar 

  30. Cicognani C, Malavolti M, Morselli-Labate AM, Zamboni L, Sama C, Barbara L (1997) Serum lipid and lipoprotein patterns in patients with liver cirrhosis and chronic active hepatitis. Arch Intern Med 157:792–796

    Article  PubMed  CAS  Google Scholar 

  31. Alvarez C, Ramos A (1986) Lipids, lipoproteins and apoproteins in serum during infection. Clin Chem 32:142–145

    PubMed  CAS  Google Scholar 

  32. Coombes EJ, Shakespeare PG, Batstone GF (1980) Lipoprotein changes after burn injury in man. J Trauma 20:971–975

    Article  PubMed  CAS  Google Scholar 

  33. Budd D, Ginsberg H (1986) Hypocholesterolemia and acute myelogenous leukemia: Association between disease activity and plasma low density lipoprotein cholesterol concentrations. Cancer 58:1361–1365

    Article  PubMed  CAS  Google Scholar 

  34. Lindh A, Lindholm M, Rossner S (1986) Intralipid disappearance in critically ill patients. Crit Care Med 14:476–480

    Article  PubMed  CAS  Google Scholar 

  35. Sun X, Oberlander D, Huang J, Weissman C (1998) Fluid resuscitation, nutritional support, and cholesterol in critically ill postsurgical patients. J Clin Anesth 10:302–308

    Article  PubMed  CAS  Google Scholar 

  36. Rosenson RS (1993) Myocardial injury: The acute phase response and lipoprotein metabolism. J Am Coll Cardiol 19:933–940

    Article  Google Scholar 

  37. Gordon BR, Parker TS, Levine DM, Saal SD, Wang JC, Sloan BJ, Barie PS, Rubin AL (1996) Low lipid concentrations in critical illness: implications for preventing and treating endotoxemia. Crit Care Med 24:584–589

    Article  PubMed  CAS  Google Scholar 

  38. Gordon BR, Parker TS, Levine DM, Saal SD, Wang JC, Sloan BJ, Barie PS, Rubin AL (2001) Relationship of hypolipidemia to cytokine concentrations and outcomes in critically ill surgical patients. Crit Care Med 29:1563–1568

    Article  PubMed  CAS  Google Scholar 

  39. Ettinger WH, Varma VK, Sorci-Thomas M, Parks JS, Sigmon RC, Smith TK, Verdery RB (1994) Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells. Arterioscler Thromb 14:8–13

    PubMed  CAS  Google Scholar 

  40. Spriggs DR, Sherman ML, Michie H (1988) Recombinant human tumor necrosis factor administered as a 24-hour intravenous infusion: A phase 1 pharmacologic study. J Natl Cancer Inst 80:1039–1044

    Article  PubMed  CAS  Google Scholar 

  41. van Gameren MM, Willemse PH, Mulder NH (1994) Effects of recombinant human interleukin-6 in cancer patients: A phase I-II study. Blood 84:1434–1441

    PubMed  Google Scholar 

  42. Nanjee MN, Crouse JR, King JM, Hovorka R, Rees SE, Carson ER, Morgenthaler JJ, Lerch P, Miller NE (1996) Effects of intravenous infusion of lipid-free apo A-I in humans. Arterioscler Thromb Vasc Biol 16:1203–1214

    PubMed  CAS  Google Scholar 

  43. DiPiro JT, Cue JI, Richards CS, Hawkins ML, Doran JE, Mansberger AR (1996) Pharmacokinetics of reconstituted human high-density lipoprotein in pigs after hemorrhagic shock with resuscitation. Crit Care Med 24:440–444

    Article  PubMed  CAS  Google Scholar 

  44. Marik PE, Zaloga GP (2001) Early enteral nutrition in acutely ill patients: A systematic review. Crit Care Med 29:2264–2270

    Article  PubMed  CAS  Google Scholar 

  45. Mesotten D, Swinnen JV, Vanderhoydonc F, Wouters PJ, van den Berghe G (2004) Contribution of circulating lipids to the improved outcome of critical illness by glycemic control with intensive insulin therapy. J Clin Endocrinol Metab 89:219–226

    Article  PubMed  CAS  Google Scholar 

  46. 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 critically ill patients. N Engl J Med 345:1359–1367

    Article  PubMed  Google Scholar 

  47. Tayek JA (2005) Lower cortisol concentrations in patients with liver disease: More adrenal failure or more confusion. Crit Care Med 33:1431–1432

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Paul E. Marik.

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The author has no financial interest in any of the products mentioned in this paper.

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Marik, P.E. Adrenal-exhaustion syndrome in patients with liver disease. Intensive Care Med 32, 275–280 (2006). https://doi.org/10.1007/s00134-005-0005-5

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