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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.

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Primary adrenal insufficiency is due to adrenal gland failure, resulting in cortisol and aldosterone deficiency. Manifestations include weakness, dehydration, hypotension, anorexia, nausea, vomiting, weight loss, and abdominal pain. Hyperpigmentation of skin and mucous membrane occurs as a result of uninhibited MSH secretion in conjunction with ATCH.

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Secondary adrenal insufficiency results from inadequate secretion of ACTH with resultant cortisol deficiency. Aldosterone levels are not significantly affected because of regulation through the renin-angiotensin system. Therefore, hyperpigmentation and hyperkalemia are not seen.

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

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Congenital adrenal hyperplasia (CAH) results from an enzyme deficiency in cortisol production. Patients typically present in the first month of life with nonspecific symptoms of lethargy, vomiting, poor feeding, and poor weight gain. Examination reveals dehydration, hyperpigmentation, and, in females, clitoromegaly.

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The diagnosis of adrenal insufficiency may be difficult because the clinical features are nonspecific. The diagnosis of primary adrenal insufficiency and CAH is based on the presence of the clinical features and lab findings of hyponatremia, hyperkalemia, hypoglycemia, anemia, metabolic acidosis, and prerenal azotemia. All patients with adrenal insufficiency have low plasma cortisol levels. Secondary adrenal insufficiency will not have findings of hyperkalemia as there is not a deficiency of aldosterone.

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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.

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Table 132-1 Causes of Primary Adrenal Insufficiency
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Table 132-2 Causes of Secondary Adrenal Insufficiency

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