Introduction
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.
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 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 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 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.
Frequency
United States
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'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.1 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.
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 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.
Clinical
History
- Prior steroid use: Use involves at least 20 mg daily of prednisone or its equivalent for at least 5 days within the past 12 months. Patients receiving doses close to normal physiologic levels require only 1 month to recover normal adrenal function.
- 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
- Topical steroids: Risk of adrenal crisis occurs when used over a large surface area for a prolonged duration, using occlusive dressings and a highly potent drug.
- Inhaled steroids
- Use of a high dose (>0.8mg/d) over a prolonged duration increases risk.
- Fluticasone may cause suppression at lower dose.
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
- Septic shock
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| References |
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References
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Further Reading
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, endocrine disorder
