Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Adrenal Crisis

  • Author: Lisa Kirkland, MD, FACP, FCCM, MSHA; Chief Editor: George T Griffing, MD  more...
 
Updated: Jun 29, 2016
 

Background

Do not confuse acute adrenal crisis with Addison disease. In 1855, Thomas Addison described a syndrome of long-term adrenal insufficiency that develops over months to years, with weakness, fatigue, anorexia, weight loss, and hyperpigmentation as the primary symptoms. In contrast, an acute adrenal crisis can manifest with vomiting, abdominal pain, and hypovolemic shock.[1, 2] When not promptly recognized, adrenal hemorrhage can be a cause of adrenal crisis. See the images below.

Computed tomographic (CT) scans of the abdomen sho Computed tomographic (CT) scans of the abdomen show normal adrenal glands several months before the onset of hemorrhage (upper panel) and enlarged adrenals 2 weeks after an acute episode of bilateral adrenal hemorrhage (lower panel). The attenuation of the adrenal glands, indicated by arrows, is increased after the acute event. Reproduced from Rao RH, Vagnucci AH, Amico JA: Bilateral massive adrenal hemorrhage: early recognition and treatment. Ann Intern Med. Feb 1 1989;110(3):227-35 with permission from the journal.

 

Next

Pathophysiology

The adrenal cortex produces 3 steroid hormones: glucocorticoids (cortisol), mineralocorticoids (aldosterone, 11-deoxycorticosterone), and androgens (dehydroepiandrosterone). The androgens are relatively unimportant in adults, and 11-deoxycorticosterone is a fairly weak mineralocorticoid in comparison with aldosterone. The primary hormone of importance in acute adrenal crisis is cortisol; adrenal aldosterone production is relatively minor.

Cortisol enhances gluconeogenesis and provides substrate through proteolysis, protein synthesis inhibition, fatty acid mobilization, and enhanced hepatic amino acid uptake. Cortisol indirectly induces insulin secretion to counterbalance hyperglycemia but also decreases insulin sensitivity. Cortisol exercises a significant anti-inflammatory effect by stabilizing lysosomes, reducing leukocytic responses, and blocking cytokine production. Phagocytic activity is preserved, but cell-mediated immunity is diminished, in situations of cortisol deficiency. Finally, cortisol facilitates free-water clearance, enhances appetite, and suppresses adrenocorticotropic hormone (ACTH) synthesis.

Aldosterone is released in response to angiotensin II stimulation via the renin-angiotensin-aldosterone system, hyperkalemia, hyponatremia, and dopamine antagonists. Its effect on its primary target organ, the kidney, is to promote reabsorption of sodium and secretion of potassium and hydrogen. The mechanism of action is unclear; an increase in the sodium- and potassium-activated adenosine triphosphatase (Na+/K+ ATPase) enzyme responsible for sodium transport, as well as increased carbonic anhydrase activity, has been suggested. The net effect is to increase intravascular volume. The renin-angiotensin-aldosterone system is unaffected by exogenous glucocorticoids, and ACTH deficiency has a relatively minor effect on aldosterone levels.

Adrenocortical hormone deficiency results in the reverse of these hormonal effects, producing the clinical findings of adrenal crisis.

Primary adrenocortical insufficiency occurs when the adrenal glands fail to release adequate amounts of these hormones to meet physiologic needs, despite release of ACTH from the pituitary. Infiltrative or autoimmune disorders are the most common cause, but adrenal exhaustion from severe chronic illness also may occur.

Secondary adrenocortical insufficiency occurs when exogenous steroids have suppressed the hypothalamic-pituitary-adrenal (HPA) axis. Too rapid withdrawal of exogenous steroid may precipitate adrenal crisis, or sudden stress may induce cortisol requirements in excess of the adrenal glands' ability to respond immediately. In acute illness, a normal cortisol level may actually reflect adrenal insufficiency because the cortisol level should be quite elevated.

Bilateral massive adrenal hemorrhage (BMAH) occurs under severe physiologic stress (eg, myocardial infarction, septic shock, complicated pregnancy) or with concomitant coagulopathy or thromboembolic disorders.

Hahner et al investigated the frequency and causes of, as well as the risk factors for, adrenal crisis in patients with chronic adrenal insufficiency. Using a disease-specific questionnaire, the authors analyzed data from 444 patients, including 254 with primary adrenal insufficiency and 190 with secondary adrenal insufficiency. At least one adrenal crisis was reported by 42% of patients, including 47% of those with primary adrenal insufficiency and 35% of patients with the secondary condition. GI infection and fever were the most common precipitating causes of crisis. Identified risk factors for adrenal crisis were, for patients with primary adrenal insufficiency, concomitant nonendocrine disease, and for patients with secondary adrenal insufficiency, female sex and diabetes insipidus.[3]

A study from the Netherlands, by Smans et al, of patients with adrenal insufficiency, found the existence of comorbidity to be the most important risk factor for adrenal crisis, with infections being the most common precipitating factors.[4]

Previous
Next

Epidemiology

Frequency

The incidence of primary adrenocortical insufficiency is variable and depends on the defining cortisol level and the method of testing (ie, ACTH stimulation versus single random cortisol level). The underlying disease also is a factor. Studies of critically ill patients with septic shock demonstrate a de novo (excluding patients with known adrenal insufficiency or patients on glucocorticoid therapy) incidence ranging from 19-54%. Secondary adrenal insufficiency has been demonstrated in 31% of patients admitted to a critical care unit.

Annane et al's landmark 2002 study found a very high rate, ie, 76% of all enrolled patients with septic shock. Of the general perioperative population, in 62,473 anesthetic administrations, only 419 (0.7%) patients required glucocorticoid supplementation and only 3 hypotensive events were thought to be attributable to glucocorticoid deficiency.[5] Studies of patients undergoing cardiac or urologic surgery reveal an incidence of 0.01-0.1%. In a study of 2000 consecutive general hospital autopsies, only 22 (1.1%) revealed bilateral adrenal hemorrhage; however, as many as 15% of patients dying in shock have been demonstrated to have BMAH.

The aforementioned study from the Netherlands, by Smans et al, found the incidence of adrenal crisis among persons with primary adrenal insufficiency to be 5.2 cases per 100 person-years, while in secondary adrenal insufficiency, the incidence was reported as 3.6 cases per 100 person-years.[4]

No description regarding racial data, sexual predilection, or age is available in the literature.

Mortality/Morbidity

In the absence of bilateral adrenal hemorrhage, the survival rate of patients with acute adrenal crisis that is diagnosed promptly and treated appropriately approaches that of patients without acute adrenal crisis with similar severity of illness. Patients who developed BMAH before the availability of hormonal testing or computed tomography (CT) scanning rarely survived. In one series, patients who were diagnosed using CT scanning had an 85% rate of survival. Because the true incidence of adrenal crisis and BMAH are unknown, the actual mortality rate also is unknown.

Previous
 
 
Contributor Information and Disclosures
Author

Lisa Kirkland, MD, FACP, FCCM, MSHA Assistant Professor, Department of Internal Medicine, Division of Hospital Medicine, Mayo Clinic; Vice Chair, Department of Critical Care, ANW Intensivists, Abbott Northwestern Hospital

Lisa Kirkland, MD, FACP, FCCM, MSHA is a member of the following medical societies: American College of Physicians, Society of Hospital Medicine, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

David M Klachko, MD, MEd Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Missouri-Columbia School of Medicine

David M Klachko, MD, MEd is a member of the following medical societies: Alpha Omega Alpha, Missouri State Medical Association, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, Endocrine Society, Sigma Xi

Disclosure: Nothing to disclose.

References
  1. Loriaux DL, Fleseriu M. Relative adrenal insufficiency. Curr Opin Endocrinol Diabetes Obes. 2009 Aug 3. [Medline].

  2. White K, Arlt W. Adrenal crisis in treated Addison's disease: a predictable but under-managed event. Eur J Endocrinol. 2010 Jan. 162(1):115-20. [Medline].

  3. Hahner S, Loeffler M, Bleicken B, et al. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010 Mar. 162(3):597-602. [Medline].

  4. Smans LC, Van der Valk ES, Hermus AR, Zelissen PM. Incidence of adrenal crisis in patients with adrenal insufficiency. Clin Endocrinol (Oxf). 2016 Jan. 84 (1):17-22. [Medline].

  5. Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21. 288(7):862-71. [Medline]. [Full Text].

  6. Weant KA, Sasaki-Adams D, Dziedzic K, et al. Acute relative adrenal insufficiency after aneurysmal subarachnoid hemorrhage. Neurosurgery. 2008 Oct. 63(4):645-9; discussion 649-50. [Medline].

  7. Guillamondegui OD, Gunter OL, Patel S, et al. Acute adrenal insufficiency may affect outcome in the trauma patient. Am Surg. 2009 Apr. 75(4):287-90. [Medline].

  8. Rushworth RL, Falhammar H, Munns CF, Maguire AM, Torpy DJ. Hospital Admission Patterns in Children with CAH: Admission Rates and Adrenal Crises Decline with Age. Int J Endocrinol. 2016. 2016:5748264. [Medline]. [Full Text].

  9. Arlt W. The approach to the adult with newly diagnosed adrenal insufficiency. J Clin Endocrinol Metab. 2009 Apr. 94(4):1059-67. [Medline].

  10. Hahner S, Allolio B. Therapeutic management of adrenal insufficiency. Best Pract Res Clin Endocrinol Metab. 2009 Apr. 23(2):167-79. [Medline].

  11. Ahlawat SK, Jain S, Kumari S, Varma S, Sharma BK. Pheochromocytoma associated with pregnancy: case report and review of the literature. Obstet Gynecol Surv. 1999 Nov. 54(11):728-37. [Medline].

  12. Aono J, Mamiya K, Ueda W. Abrupt onset of adrenal crisis during routine preoperative examination in a patient with unknown Addison's disease. Anesthesiology. 1999 Jan. 90(1):313-4. [Medline].

  13. Arafah BM. Hypothalamic pituitary adrenal function during critical illness: limitations of current assessment methods. J Clin Endocrinol Metab. 2006 Oct. 91(10):3725-45. [Full Text].

  14. Axelrod L. Perioperative management of patients treated with glucocorticoids. Endocrinol Metab Clin North Am. 2003 Jun. 32(2):367-83. [Medline].

  15. Chin R. Adrenal crisis. Crit Care Clin. 1991 Jan. 7(1):23-42. [Medline].

  16. Cronin CC, Callaghan N, Kearney PJ, et al. Addison disease in patients treated with glucocorticoid therapy. Arch Intern Med. 1997 Feb 24. 157(4):456-8. [Medline].

  17. Iga K, Hori K, Gen H. Deep negative T waves associated with reversible left ventricular dysfunction in acute adrenal crisis. Heart Vessels. 1992. 7(2):107-11. [Medline].

  18. Koo DJ, Jackman D, Chaudry IH, Wang P. Adrenal insufficiency during the late stage of polymicrobial sepsis. Crit Care Med. 2001 Mar. 29(3):618-22. [Medline].

  19. Kromah F, Tyroch A, McLean S, Hughes H, Flavin N, Lee S. Relative adrenal insufficiency in the critical care setting: debunking the classic myth. World J Surg. 2011 Aug. 35(8):1818-23. [Medline].

  20. Nicholson G, Burrin JM, Hall GM. Peri-operative steroid supplementation. Anaesthesia. 1998 Nov. 53(11):1091-104. [Medline].

  21. Obenour RA, Ross S. Adrenal Crisis. Hospital Formulary of the University of Tennessee Medical Center. 1999. [Full Text].

  22. Passmore JM Jr. Adrenal Cortex. Clinics in Critical Care Medicine. 1985. 97-134.

  23. Rao RH. Bilateral massive adrenal hemorrhage. Med Clin North Am. 1995 Jan. 79(1):107-29. [Medline].

  24. Rao RH, Vagnucci AH, Amico JA. Bilateral massive adrenal hemorrhage: early recognition and treatment. Ann Intern Med. 1989 Feb 1. 110(3):227-35. [Medline].

  25. Schroeder S, Wichers M, Klingmuller D, et al. The hypothalamic-pituitary-adrenal axis of patients with severe sepsis: altered response to corticotropin-releasing hormone. Crit Care Med. 2001 Feb. 29(2):310-6. [Medline].

  26. Vella A, Nippoldt TB, Morris JC 3rd. Adrenal hemorrhage: a 25-year experience at the Mayo Clinic. Mayo Clin Proc. 2001 Feb. 76(2):161-8. [Medline].

  27. Williams GH, Dluhy RG. Disease of the Adrenal Cortex. In: Braunwald E, Fauci AS, Kasper DL, eds. Harrison's Principles of Internal Medicine. 13th ed. New York, NY: McGraw-Hill; 1994. 1953-76.

  28. Xarli VP, Steele AA, Davis PJ, et al. Adrenal hemorrhage in the adult. Medicine (Baltimore). 1978 May. 57(3):211-21. [Medline].

  29. Zaloga GP. In: Zaloga G, MacGregor D, eds. The Critical Care Drug Handbook. New York, NY: Mosby Yearbook; 1991.

 
Previous
Next
 
Computed tomographic (CT) scans of the abdomen show normal adrenal glands several months before the onset of hemorrhage (upper panel) and enlarged adrenals 2 weeks after an acute episode of bilateral adrenal hemorrhage (lower panel). The attenuation of the adrenal glands, indicated by arrows, is increased after the acute event. Reproduced from Rao RH, Vagnucci AH, Amico JA: Bilateral massive adrenal hemorrhage: early recognition and treatment. Ann Intern Med. Feb 1 1989;110(3):227-35 with permission from the journal.
Enlarged, dense, suprarenal masses
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.