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Adrenal insufficiency results when the physiologic demand for glucocorticoids and mineralocorticoids exceeds the supply from the adrenal cortex. The pituitary secretes adrenocorticotropin hormone (ACTH) and associated melanocyte stimulating hormone (MSH). ACTH stimulates the adrenal cortex to secrete cortisol. Cortisol has negative feedback on the pituitary to inhibit secretion of ACTH and MSH.


Primary adrenal insufficiency is due to adrenal gland failure, resulting in low cortisol and aldosterone production. Clinical features include weakness, dehydration, hypotension, anorexia, nausea, vomiting, weight loss, and abdominal pain. Hyperpigmentation of skin and mucous membranes occurs as a result of uninhibited MSH secretion in conjunction with ACTH.

Secondary adrenal insufficiency results from inadequate secretion of ACTH with resultant cortisol deficiency. Aldosterone levels are not affected because of regulation by the renin-angiotensin axis and serum potassium levels. Therefore, hyperpigmentation and hyperkalemia do not occur.

Adrenal crisis is the acute, life-threatening form of adrenal insufficiency. Clinical features described above are severe and accompanied by shock and altered mental status.


All patients with adrenal insufficiency have low plasma cortisol levels. The ACTH level is high in primary and low in secondary adrenal insufficiency. Cortisol and ACTH levels are usually not available in the emergency department, so the diagnosis of primary adrenal insufficiency is based on the presence of the clinical features and lab findings of hyponatremia, hyperkalemia, hypoglycemia, anemia, metabolic acidosis, and prerenal azotemia. Secondary adrenal insufficiency is similarly diagnosed, but hyperkalemia is not seen as aldosterone secretion is normal.

The most common cause of acute adrenal insufficiency is adrenal suppression from prolonged steroid use with either abrupt steroid withdrawal or exposure to increased physiologic stress such as injury, illness, or surgery. It may take up to 1 year for the hypothalamic-pituitary-adrenal axis to recover following prolonged suppression with steroid treatment. Tables 132-1 and 132-2 list causes of primary and secondary adrenal insufficiency, respectively. Consider the diagnosis of adrenal crisis in any patient with unexplained hypotension refractory to pressors, especially if one of the causes listed is known to exist.

Table 132-1

Causes of Primary Adrenal Insufficiency

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