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Key Points

  • Adrenal crisis is a medical emergency and must be recognized and treated promptly.

  • Administration of steroids, saline, and vasopressors (as needed) should be instituted when adrenal crisis is suspected.

  • Adrenal crisis should be considered in the presence of refractory hypotension.

  • The preferred steroid for adrenal insufficiency is dexamethasone because it does not interfere with the cosyntropin stimulation test.


Cortisol secretion is regulated by adrenocorticotropic hormone (ACTH), which, in turn, is regulated by corticotrophin-releasing hormone (CRH) from the hypothalamus. Aldosterone secretion is regulated by the renin-angiotensin system.

Adrenal insufficiency is the failure of the adrenal cortex to produce adequate amounts of cortisol, aldosterone, or both. Primary adrenal insufficiency (Addison disease) refers to failure of the adrenal gland as a result of tissue destruction, most frequently from an autoimmune process (70% of cases). It is uncommon, affecting 100 per 1 million persons. Risk factors for primary adrenal insufficiency include human immunodeficiency virus (HIV) infection, metastatic cancer (lung, breast, leukemia), infection (bacterial, fungal, viral, tuberculosis), sarcoidosis, or sepsis. HIV infection results in adrenal insufficiency at a much higher rate than in the general population. Up to 25% of patients with HIV have inadequate adrenal reserves. Contributing factors in HIV patients include the human immunodeficiency virus itself, opportunistic infections, and medications.

Secondary adrenal insufficiency is due to inadequate production of ACTH from the pituitary gland. Cortisol production is decreased; however, aldosterone secretion is usually intact because its production is stimulated to a much greater extent by angiotensin. Suppression of the hypothalamic-pituitary-adrenal axis by exogenous steroid administration is the most common cause of adrenal insufficiency. It is based on the dose and duration of treatment. Administrations of steroids for <2 weeks or doses <5 mg per day are unlikely to result in adrenal insufficiency. Steroid administration (withdrawal), pituitary tumors, and trauma place patients at risk for secondary adrenal insufficiency.

Acute adrenal insufficiency (Addison or adrenal crisis) is an emergent condition that occurs in a person who has underlying adrenal suppression who undergoes an acute stress or illness. Some patients have a history of chronic adrenal insufficiency; for others, adrenal crisis is the initial presentation.

Cushing syndrome refers to a situation in which there is a symptomatic excess of glucocorticoids. Prolonged exogenous administration of steroids is the most common cause of Cushing syndrome. Cushing disease is present when Cushing syndrome is due to excessive ACTH secretion from the pituitary gland. Endogenous Cushing syndrome (Cushing disease) is much less common and occurs in 13 per 1 million persons.

In addition to exogenous steroid administration, Cushing syndrome is due to an ACTH-producing tumor of the pituitary gland (70%), adrenal gland (15%), or other (15%). Other tumors producing ACTH include pancreatic cancer, small-cell lung carcinoma, and carcinoid tumors.

Prolonged steroid administration is a risk factor for exogenous Cushing syndrome. Endogenous (Cushing disease) ...

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