title: Update on adrenal insufficiency in patients with liver cirrhosis.
abstract: Liver cirrhosis is a major cause of mortality worldwide, often with severe sepsis as the terminal event. Over the last two decades, several studies have reported that in septic patients the adrenal glands respond inappropriately to stimulation, and that the treatment with corticosteroids decreases mortality in such patients. Both cirrhosis and septic shock share many hemodynamic abnormalities such as hyperdynamic circulatory failure, decreased peripheral vascular resistance, increased cardiac output, hypo-responsiveness to vasopressors, increased levels of proinflammatory cytokines [interleukine(IL)-1, IL-6, tumor necrosis factor-alpha] and it has, consequently, been reported that adrenal insufficiency (AI) is common in critically ill cirrhotic patients. AI may also be present in patients with stable cirrhosis without sepsis and in those undergoing liver transplantation. The term hepato-adrenal syndrome defines AI in patients with advanced liver disease with sepsis and/or other complications, and it suggests that it could be a feature of liver disease per se, with a different pathogenesis from that of septic shock. Relative AI is the term given to inadequate cortisol response to stress. More recently, another term is used, namely "critical illness related corticosteroid insufficiency" to define "an inadequate cellular corticosteroid activity for the severity of the patient's illness". The mechanisms of AI in liver cirrhosis are not completely understood, although decreased levels of high-density lipoprotein cholesterol and high levels of proinflammatory cytokines and circulatory endotoxin have been suggested. The prevalence of AI in cirrhotic patients varies widely according to the stage of the liver disease (compensated or decompensated, with or without sepsis), the diagnostic criteria defining AI and the methodology used. The effects of corticosteroid therapy on cirrhotic patients with septic shock and AI are controversial. This review aims to summarize the existing published information regarding AI in patients with liver cirrhosis.
authors: Institute of Gastroenterology and Hepatology, "Gr. T. Popa" University of Medicine and Pharmacy, "St. Spiridon" University Hospital, 700111 Iaşi, Romania.
authors: Anca
authors: A
authors: Trifan
authors: Stefan
authors: S
authors: Chiriac
authors: Carol
authors: C
authors: Stanciu
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000309:Adrenal Insufficiency / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology; D012772:Shock, Septic / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D006854:Hydrocortisone
keywords: Adrenal insufficiency; Corticosteroid therapy; Liver cirrhosis; Septic shock
references: Cardiovasc Res. 1999 Jan;41(1):55-64
references: 10325953
references: J Clin Endocrinol Metab. 2007 Aug;92(8):2965-71
references: 17535998
references: Physiol Rev. 1999 Jan;79(1):1-71
references: 9922367
references: Intensive Care Med. 2011 Dec;37(12):1986-93
references: 21850531
references: N Engl J Med. 1987 Sep 10;317(11):659-65
references: 2888017
references: Hepatology. 2003 Jan;37(1):208-17
references: 12500206
references: Crit Care Med. 2008 Jun;36(6):1937-49
references: 18496365
references: N Engl J Med. 2004 Apr 15;350(16):1629-38
references: 15084695
references: Curr Opin Crit Care. 2007 Aug;13(4):363-9
references: 17599004
references: Crit Care Med. 2003 May;31(5):1359-66
references: 12771603
references: J Gastroenterol Hepatol. 2012 Oct;27(10):1543-4
references: 22994431
references: Br J Clin Pharmacol. 1998 Dec;46(6):589-97
references: 9862249
references: Best Pract Res Clin Endocrinol Metab. 2001 Dec;15(4):513-31
references: 11800521
references: N Engl J Med. 2008 Jan 10;358(2):111-24
references: 18184957
references: Eur J Gastroenterol Hepatol. 2003 May;15(5):495-501
references: 12702906
references: N Engl J Med. 2009 May 28;360(22):2328-39
references: 19474430
references: BMJ. 2004 Aug 28;329(7464):480
references: 15289273
references: Crit Care Med. 2005 Nov;33(11):2457-64
references: 16276166
references: Shock. 2012 Jan;37(1):28-33
references: 21993448
references: JAMA. 2000 Feb 23;283(8):1038-45
references: 10697064
references: Hepatology. 2006 Apr;43(4):673-81
references: 16557538
references: J Hepatol. 2007 Sep;47(3):418-23
references: 17629587
references: N Engl J Med. 2003 Feb 20;348(8):727-34
references: 12594318
references: Liver Transpl. 2008 Jul;14(7):1014-9
references: 18581463
references: Ann Hepatol. 2007 Jul-Sep;6(3):194-5
references: 17786150
references: Liver Transpl. 2006 Dec;12(12):1896-9
references: 17133575
references: J Steroid Biochem. 1987 Feb;26(2):197-202
references: 3560936
references: J Biol Chem. 2003 Jun 20;278(25):22771-80
references: 12651854
references: Hepatology. 2006 Nov;44(5):1288-95
references: 17058239
references: Ann Intern Med. 2003 Aug 5;139(3):194-204
references: 12899587
references: J Clin Invest. 1960 Feb;39:320-31
references: 14432260
references: Crit Care Med. 1995 Jul;23(7):1294-303
references: 7600840
references: Pharmacol Ther. 2001 Mar;89(3):221-31
references: 11516477
references: Transplantation. 1995 Jun 27;59(12):1744-5
references: 7604447
references: Acta Anaesthesiol Scand. 2008 Jan;52(1):45-51
references: 17996000
references: Endocrinol Metab Clin North Am. 2005 Jun;34(2):293-313, viii
references: 15850843
references: Crit Care Med. 1999 Apr;27(4):723-32
references: 10321661
references: Intensive Care Med. 1994;20(2):138-41
references: 8201094
references: Ann Intern Med. 2004 Jul 6;141(1):47-56
references: 15238370
references: Crit Care. 2002 Oct;6(5):434-8
references: 12398784
references: Hepatology. 2012 Apr;55(4):1282-91
references: 22234976
references: J Gastroenterol Hepatol. 2008 Dec;23(12):1901-8
references: 18554237
references: Crit Care Med. 2007 Aug;35(8):1896-903
references: 17568326
references: Crit Care Med. 2005 Jun;33(6):1254-9
references: 15942340
references: Crit Care. 2004 Apr;8(2):122-9
references: 15025773
references: Intensive Care Med. 2003 Dec;29(12):2199-2203
references: 14566456
references: J Hepatol. 2010 Jun;52(6):839-45
references: 20385427
references: Liver Int. 2003 Apr;23(2):71-7
references: 12654129
references: J Gastroenterol Hepatol. 1993 May-Jun;8(3):247-53
references: 8390870
references: Curr Vasc Pharmacol. 2004 Jan;2(1):1-12
references: 15320828
references: N Engl J Med. 1995 May 18;332(20):1351-62
references: 7715646
references: Intensive Care Med. 2006 Feb;32(2):275-280
references: 16432671
references: Hepatology. 2009 Dec;50(6):2022-33
references: 19885876
references: Intensive Care Med. 2008 Jan;34(1):61-9
references: 18000649
references: Immunopharmacology. 1995 Mar;29(2):93-101
references: 7775161
references: J Clin Endocrinol Metab. 2006 Jan;91(1):43-7
references: 16249286
references: CMAJ. 2010 Dec 14;182(18):1971-7
references: 21059778
references: Ann Clin Biochem. 2009 Nov;46(Pt 6):505-7
references: 19726458
references: Arterioscler Thromb. 1994 Jan;14(1):8-13
references: 8274481
references: JAMA. 2002 Aug 21;288(7):862-71
references: 12186604
references: Intensive Care Med. 2008 Jan;34(1):116-24
references: 17906854
references: Lancet. 1991 Mar 9;337(8741):582-3
references: 1671944
references: Proc Natl Acad Sci U S A. 1990 Dec;87(24):10043-7
references: 1702214
references: J Clin Endocrinol Metab. 2006 Oct;91(10):3725-45
references: 16882746
references: Am J Respir Crit Care Med. 2003 Feb 15;167(4):512-20
references: 12426230
references: Endocrinology. 1990 Jul;127(1):101-6
references: 2163305
references: Liver Int. 2011 Mar;31(3):425-33
references: 21281437
references: J Hepatol. 2011 Feb;54(2):243-50
references: 21056503
references: J Hepatol. 2001 Jan;34(1):32-7
references: 11211904
references: Clin Gastroenterol Hepatol. 2011 Jul;9(7):595-601
references: 21545846
references: J Gastroenterol Hepatol. 2012 Oct;27(10):1596-601
references: 22647073
references: J Clin Endocrinol Metab. 2003 May;88(5):2045-8
references: 12727952
references: Clin Chem Lab Med. 2003 Feb;41(2):146-51
references: 12666999
references: Am J Respir Crit Care Med. 2005 Feb 1;171(3):242-8
references: 15557131
references: Crit Care Med. 2003 Jan;31(1):141-5
references: 12545007
references: Life Sci. 1998;62(16):1387-95
references: 9585166
references: Hepatology. 2008 Dec;48(6):1924-31
references: 19003911
references: J Hepatol. 2010 Nov;53(5):841-8
references: 20739086
references: Crit Care. 2002 Jun;6(3):251-9
references: 12133187
references: Gastroenterol Clin Biol. 2009 Jun-Jul;33(6-7):584-8
references: 19473798
references: Intensive Care Med. 1991;17(7):436-7
references: 1774404
references: Crit Care Med. 1995 Aug;23(8):1430-9
references: 7634816
references: Crit Care Med. 2005 Aug;33(8):1688-93
references: 16096442
references: Hepatology. 2013 Nov;58(5):1757-65
references: 23728792
references: J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):11-21
references: 17070034
references: Arch Intern Med. 1997 Apr 14;157(7):792-6
references: 9125012
references: Infect Immun. 2002 Jun;70(6):2995-3003
references: 12010990
references: Am J Med. 1995 Mar;98(3):266-71
references: 7872343
references: Sao Paulo Med J. 2007 Jul 5;125(4):237-41
references: 17992396
references: Liver Int. 2012 Jan;32(1):128-36
references: 22098564
references: Chest. 2009 Jan;135(1):181-193
references: 19136406
references: Crit Care Med. 2004 Sep;32(9):1977-8; author reply 1978-9
references: 15343040
references: Chest. 2002 Nov;122(5):1784-96
references: 12426284
references: J Hepatol. 2012 Jun;56(6):1299-304
references: 22314431
references: Clin Pharmacol Ther. 2000 Sep;68(3):293-303
references: 11014411
references: Crit Care Med. 1998 Apr;26(4):645-50
references: 9559600
references: J Clin Endocrinol Metab. 2008 Nov;93(11):4245-53
references: 18697868