Adrenal Insufficiency

  • Gary P. Zaloga
  • Paul Marik


Cortisol is an essential hormone required for normal function of all cells in the body. It is required for carbohydrate, protein, and lipid metabolism; immune function; synthesis of catecholamines and adrenergic receptors; and numerous other functions. As such, cortisol is necessary for the response to injury and illness; a deficiency impairs recovery and increases morbidity and mortality.


Septic Shock Cortisol Level Critical Illness Cortisol Response Cortisol Secretion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Oelkers W. Adrenal insufficiency. N Engl J Med 1996; 335: 1206–12.PubMedCrossRefGoogle Scholar
  2. 2.
    Membreno L, Irony I, Dere W, Klein R, Biglieri EG, Cobb E. Adrenocortical function in the acquired immunodeficiency syndrome. J Clin Endocrinol Metab 1987; 65: 482–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Soni A, Pepper GM, Wyrwinski PM, Ramirez NE, Simon R, Pina T, Gruenspan H, Vaca CE. Adrenal insufficiency occurring during septic shock: incidence, outcome, and relationship to peripheral cytokine levels. Am J Med 1995; 98: 266–71.PubMedCrossRefGoogle Scholar
  4. 4.
    Bateman A, Singh A, Kral T, Solomon S. The immune-hypothalamic-pituitary-adrenal axis. Endocr Rev 1989; 10: 92–112.PubMedCrossRefGoogle Scholar
  5. 5.
    Darling G, Goldstein DS, Stull R, Gorschboth CM, Norton JA. Tumor necrosis factor: immune endocrine interaction. Surgery 1989; 106: 1155–60.PubMedGoogle Scholar
  6. 6.
    Sharp BM, Matta SG, Peterson PK, Newton R, Chao C, Mcallen K. Tumor necrosis factor-alpha is a potent ACTH secretagogue: comparison to interleukin-1 beta. Endocrinology 1989; 124: 3131–3.PubMedCrossRefGoogle Scholar
  7. 7.
    Gaillard RC, Turnill D, Sappino P, Muller AF. Tumor necrosis factor alpha inhibits the hormonal response of the pituitary gland to hypothalamic releasing factors. Endocrinology 1990; 127: 101–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Richards ML, Caplan RH, Wickus GG, Lambert PJ, Kisken WA. The rapid low-dose (1 microgram) cosyntropin test in the immediate postoperative period: results in elderly subjects after major abdominal surgery. Surgery 1999; 125: 431–40.PubMedCrossRefGoogle Scholar
  9. 9.
    Zhu Q, Solomon S. Isolation and mode of action of rabbit corticostatin (antiadrenocorticotropin) peptides. Endocrinology 1992; 130: 1413–23.PubMedCrossRefGoogle Scholar
  10. 10.
    Jaattela M, Ilvesmaki V, Voutilainen R, Stenman UH, Saksela E. Tumor necrosis factor as a potent inhibitor of adrenocorticotropin-induced cortisol production and steroidogenic P450 enzyme gene expression in cultured human fetal adrenal cells. Endocrinology 1991; 128: 623–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Natarajan R, Ploszaj S, Horton R, Nadler J. Tumor necrosis factor and interleukin-1 are potent inhibitors of angiotensin II-induced aldosterone synthesis. Endocrinology 1989; 125: 3084–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Jaattela M, Carpen O, Stenman UH, Saksela E. Regulation of ACTH-induced steroidogenesis in human fetal adrenals by rTNF-alpha. Mol Cell Endocrinol 1990; 68: R31 - R36.PubMedCrossRefGoogle Scholar
  13. 13.
    Tominaga T, Fukata J, Hayashi Y, Satoh Y, Fuse N, Segawa H, Ebisui O, Nakai Y, Osamura Y, Imura H. Distribution and characterization of immunoreactive corticostatin in the hypothalamicpituitary-adrenal axis. Endocrinology 1992; 130: 1593–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Keri G, Parameswaran V, Trunkey DD, Ramachandran J. Effects of septic shock plasma on adrenocortical cell function. Life Sci 1981; 28: 1917–23.PubMedCrossRefGoogle Scholar
  15. 15.
    Catalano RD, Parameswaran V, Ramachandian J, Trunkey DD. Mechanisms of adrenocortical depression during Escherichia coli shock. Arch Surg 1984; 119: 145–50.PubMedCrossRefGoogle Scholar
  16. 16.
    Sibbald WJ, Short A, Cohen MP, Wilson RF. Variations in adrenocortical responsiveness during severe bacterial infections. Unrecognized adrenocortical insufficiency in severe bacterial infections. Ann Surg 1977; 186: 29–33.PubMedCrossRefGoogle Scholar
  17. 17.
    Parker LN, Levin ER, Lifrak ET. Evidence for adrenocortical adaptation to severe illness. J Clin Endocrinol Metab 1985; 60: 947–52.PubMedCrossRefGoogle Scholar
  18. 18.
    Drucker D, McLaughlin J. Adrenocortical dysfunction in acute medical illness. Crit Care Med 1986; 14: 789–91.PubMedCrossRefGoogle Scholar
  19. 19.
    Rivers EP, Gaspari M, Saad GA, Menarnek M, Fath J, Horst HM, Wortsman J. Adrenal insufficiency in high risk surgical intensive care unit patients. Crit Care Med (in press).Google Scholar
  20. 20.
    Beishuizen A, Vermes I, Hylkema BS, Haanen C. Relative eosinophilia and functional adrenal insufficiency in critically ill patients. Lancet 1999; 353: 1675–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Marik PE, Kiminyo K, Olexo S, Zaloga GP. Occult adrenal insufficiency (AI) in critically ill patients: an underdiagnosed entity. Crit Care Med 1999; 27: A141.CrossRefGoogle Scholar
  22. 22.
    McKee JI, Finlay WE. Cortisol replacement in severely stressed patients. Lancet 1983; 1: 484.PubMedCrossRefGoogle Scholar
  23. 23.
    Lamberts SW, Bruining HA, de Jong FH. Corticosteroid therapy in severe illness. N Engl J Med 1997; 337: 1285–92.Google Scholar
  24. 24.
    Reincke M, Allolio B, Wurth G, Winkelmann W. The hypothalamic-pituitary-adrenal axis in critical illness: response to dexamethasone and corticotropin-releasing hormone. J Clin Endocrinol Metab 1993; 77: 151–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Naito Y, Fukata J, Tamai S, Seo N, Nakai Y, Mori K, Imura H. Biphasic changes in hypothalamopituitary-adrenal function during the early recovery period after major abdominal surgery. J Clin Endocrinol Metab 1991; 73: 111–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Williams MD, Acosta JA, Herr DL. Gender differences exist in serum cortisol levels of critically ill surgical patients. Crit Care Med 1999; 27: A147.CrossRefGoogle Scholar
  27. 27.
    Vernies I, Beishuizen A, Hampsink RM, Haanen C. Dissociation of plasma adrenocorticotropin and cortisol levels in critically ill patients: possible role of endothelia and atrial natriuretic hormone. J Clin Endocrinol Metab 1995; 80: 1238–42.CrossRefGoogle Scholar
  28. 28.
    Grinspoon SK, Biller BM. Laboratory assessment of adrenal insufficiency. J Clin Endocrinol Metab 1994; 79: 923–31.PubMedCrossRefGoogle Scholar
  29. 29.
    Streeten DH. What test for hypothalamic-pituitary-adrenocortical insufficiency? Lancet 1999; 354: 179–80.PubMedCrossRefGoogle Scholar
  30. 30.
    Streeten DH, Anderson GH Jr, Bonaventura MM. The potential serious consequences from misinterpreting normal responses to the rapid adrenocorticotropin test. J Clin Endocrinol Metab 1996; 81: 285–90.PubMedCrossRefGoogle Scholar
  31. 31.
    Donald RA, Perry EG, Wittert GA, Chapman M, Livesey JH, Ellis MJ, Evans MJ, Yandle T, Espiner EA. The plasma ACTH, AVP, CRH and catecholamine responses to conventional and laparoscopic cholecystectomy. Clin Endocrinol (Oxf) 1993; 38: 609–15.CrossRefGoogle Scholar
  32. 32.
    Borst GC, Michenfelder HJ, O’Brian JT. Discordant cortisol response to exogenous ACTH and insulin-induced hypoglycemia in patients with pituitary disease. N Engl J Med 1982; 306: 1462–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Kidess AI, Caplan RH, Reynertson RH, Wickus GG, Goodnough DE. Transient corticotropin deficiency in critical illness. Mayo Clin Proc 1993; 68: 435–41.PubMedCrossRefGoogle Scholar
  34. 34.
    Reschini E, Catania A, Giustina G. Plasma cortisol response to ACTH does not accurately indicate the state of hypothalamic-pituitary-adrenal axis. J Endocrinol Invest 1982; 5: 259–61.PubMedGoogle Scholar
  35. 35.
    Cunningham SK, Moore A, McKenna TJ. Normal cortisol response to corticotropin in patients with secondary adrenal failure. Arch Intern Med 1983; 143: 2276–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Hjortrup A, Kehlet H, Lindholm J, Stentoft P. Value of the 30-minute adrenocorticotropin (ACTH) test in demonstrating hypothalamic-pituitary-adrenocortical insufficiency after acute ACTH deprivation. J Clin Endocrinol Metab 1983; 57: 668–70.PubMedCrossRefGoogle Scholar
  37. 37.
    Oetkers W, Boelke T, Bahr V. Dose-response relationships between plasma adrenocorticotropin (ACTH), cortisol, aldosterone, and 18-hydroxycorticosterone after injection of ACTH-(1–39) or human corticotropin releasing hormone in man. J Clin Endocrinol Metab 1988; 66: 181–6.CrossRefGoogle Scholar
  38. 38.
    Tordjman K, Jaffe A, Grazas N, Apter C, Stem N. The role of the low dose (1 microgram) adrenocorticotropin test in the evaluation of patients with pituitary diseases. J Clin Endocrinol Metab 1995; 80: 1301–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Broide J, Soferman R, Kivity S, Golander A, Dickstein G, Spirer Z, Weisman Y. Low-dose adrenocorticotropin test reveals impaired adrenal function in patients taking inhaled corticosteroids. J Clin Endocrinol Metab 1995; 80: 1243–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Dickstein G, Shechner C, Nicholson WE, Rosner I, Shen-Orr Z, Adawi F, Lahav M. Adrenocorticotropin stimulation test: effects on basal cortisol level, time of the day, and suggested new low dose test. J Clin Endocrinol Metab 1991; 72: 773–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Rasmuson S, Olsson T, Hagg E. A low dose ACTH test to assess the function of the hypothalamic- pituitary-adrenal axis. Clin Endocrinol (Oxf) 1996; 44: 151–6.CrossRefGoogle Scholar
  42. 42.
    Ledingham IM, Watt I. Influence of sedation on mortality in critically ill multiple trauma patients. Lancet 1983; 1: 1270.PubMedCrossRefGoogle Scholar
  43. 43.
    Briegel J, Forst H, Haller M, Schelling G, Kilger E, Kuprat G, Hemmer B, Hummel T, Lenhart A, Heyduck M, Stoll C, Peter K. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med 1999; 27: 723–32.PubMedCrossRefGoogle Scholar
  44. 44.
    The Veterans Administration Systemic Sepsis Cooperative Study Group. Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N Engl J Med 1987; 317: 659–65.Google Scholar
  45. 45.
    Bone RC, Fisher CJ Jr, Clemmer TP, Slotman GJ, Metz CA, Balk RA. A controlled clinical trial of high dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 1987; 317: 653–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Gary P. Zaloga
    • 1
  • Paul Marik
    • 1
  1. 1.Washington Hospital CenterUSA

Personalised recommendations