Addison’s disease occurs when more than 90% of the adrenal gland is destroyed. Such massive destruction usually results from an autoimmune process in which circulating antibodies react specifically against the adrenal tissue.

Other causes include tuberculosis, bilateral adrenalectomy, hemorrhage into the adrenal gland, metastatic tumors such as lung and breast carcinoma, infections, such as histoplasmosis, human immunodeficiency virus, and cytomegalovirus and, rarely, a familial tendency toward autoimmune disease.

Secondary adrenal hypofunction that results in glucocorticoid deficiency can stem from hypopituitarism (causing decreased corticotropin secretion), from abrupt withdrawal of long-term corticosteroid therapy (long-term exogenous corticosteroid stimulation suppresses pituitary corticotropin secretion and causes adrenal gland atrophy), or from removal of a nonendocrine, corticotropin-secreting tumor.

Adrenal crisis occurs in a patient with adrenal hypofunction when trauma, surgery, or other physiologic stress exhausts the body’s stores of glucocorticoids.

Adrenal crisis, caused by a critical deficiency of mineralocorticoids and glucocorticoids, is the most serious complication of adrenal hypofunction. Without immediate, vigorous treatment, adrenal crisis leads to vascular collapse, renal failure, coma, and death. Other complications of adrenal hypofunction include hyperpyrexia and psychotic reactions.

Assessment of patient history for adrenal hypofunction may reveal synthetic steroid use, adrenal surgery, or recent infection. The patient may complain of muscle weakness, fatigue, light-headedness when rising from a chair or bed, weight loss, cravings for salty food, decreased tolerance for even minor stress, and various GI disturbances, such as nausea, vomiting, anorexia, and chronic diarrhea. He may also complain of anxiety, irritability, and confusion. Reduced urine output and other symptoms of dehydration may occur. Female patients may have decreased libido due to reduced androgen production, and amenorrhea.

In female patients, inspection may reveal poor coordination, dry skin and mucous membranes related to dehydration, and decreased axillary and pubic hair. The patient with Addison’s disease typically has a conspicuous bronze coloration of the skin that resembles a deep suntan, especially in the creases of the hands and over the metacarpophalangeal joints, elbows, and knees. He may also exhibit a darkening of scars, areas of vitiligo (absence of pigmentation), and increased pigmentation of the mucous membranes, especially the buccal mucosa.

This abnormal coloration results from decreased secretion of cortisol (one of the glucocorticoids), which causes the pituitary gland to simultaneously secrete excessive amounts of melanocytestimulating hormone (MSH) and corticotropin. Secondary adrenal hypofunction doesn’t cause hyperpigmentation because corticotropin and MSH levels are low.

Palpation may disclose a weak, irregular pulse, and auscultation of blood pressure reveals hypotension.

Diagnosis requires demonstration of decreased corticosteroid concentrations in plasma or urine and an accurate classification of adrenal hypofunction as primary or secondary. After baseline plasma and urine steroid testing, the tests listed below follow: