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Adrenal Crisis

Adrenal Crisis excerpt Synonyms and related keywords: acute adrenal crisis, acute adrenocortical insufficiency, acute adrenal insufficiency, addisonian crisis, adrenal apoplexy, cortisol, aldosterone, primary adrenocortical insufficiency, secondary adrenocortical insufficiency, bilateral massive adrenal hemorrhage, BMAH

AUTHOR INFORMATION

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Author: Lisa Kirkland, MD, Senior Associate Consultant, Department of Internal Medicine, Division of Area Internal Medicine, Mayo Clinic, Rochester

Lisa Kirkland, MD, is a member of the following medical societies:

• American College of Physician Executives,
• American College of Physicians-American Society of Internal Medicine,
• Medical Society of Virginia,
• Society of Critical Care Medicine, and
• Southern Medical Association

Editor(s):

• David M Klachko, MBBCh, Associate Fellowship Director, Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Missouri;
• Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, Pharmacy, eMedicine;
• Don S Schalch, MD, Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics;
• Mark Cooper, MD, Head, Vascular Division, Baker Medical Research Institute; Professor of Medicine, Monash University; and
• George T Griffing, MD, Director, Division of General Internal Medicine, Professor, Department of Internal Medicine, St Louis University

INTRODUCTION

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Background: Do not confuse acute adrenal crisis with Addison disease. In 1855, Thomas Addison described a syndrome of long-term adrenal insufficiency, which develops over months to years, with weakness, fatigue, anorexia, weight loss, and hyperpigmentation as the primary symptoms. In contrast, an acute adrenal crisis can present with vomiting, abdominal pain, and hypovolemic shock.

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 to aldosterone. The hormones of importance in acute adrenal crisis are cortisol and aldosterone.

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 also has a significant anti-inflammatory effect through 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, 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.

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.

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

Frequency:

• In the US: 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. 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.

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

• Internationally: International incidence is similar to that in the United States.

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 CT scan 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.

CLINICAL

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History:

• Prior steroid use

• Severe physiologic stress (eg, sepsis, trauma, burns, surgery),
• organisms associated with adrenal crisis (eg,
  • Haemophilus influenzae,
  • Staphylococcus aureus,
  • Streptococcus pneumonia,
  • fungi),
  meningococcemia

• Azotemia

• Anticoagulants, hemorrhagic diathesis

• Newborn, complicated pregnancy

• Adrenocorticotropin therapy, known primary or secondary adrenocortical insufficiency

• AIDS

• Invasive or infiltrative disorders

• Tuberculosis

Physical:

• Unexplained shock, usually refractory to fluid and pressor resuscitation

• Nausea, vomiting, abdominal or flank pain

• Hyperthermia or hypothermia

Causes:

• Rapid withdrawal of long-term steroid therapy

• Ketoconazole

• Phenytoin

• Rifampin

• Mitotane

DIFFERENTIALS

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Septic Shock

Other Problems to be Considered:

Acute abdomen