This patient has signs and symptoms of Addison disease, or primary adrenal insufficiency, which results in decreased production of androgen, cortisol, and mineralocorticoids. The most common cause is autoimmune destruction of the adrenal gland. Other causes include adrenoleukodystrophy, hemorrhage, infection, medications, and metastatic cancer. It develops insidiously, and it may present with subtle and nonspecific signs and symptoms, including anorexia, fatigue, GI disturbances, postural dizziness, skin hyperpigmentation, and weight loss. It can also present acutely following a stressful event or illness with life-threatening addisonian or adrenal crisis characterized by hypotension, shock, and volume depletion. Common laboratory abnormalities include hyponatremia and hyperkalemia. Once suspected, the next step in diagnosis is to obtain a serum cortisol level at 8 am. Normally, serum cortisol peaks in the early morning, so a low early morning level is highly suggestive of adrenal insufficiency. If the cortisol level is low, a cosyntropin stimulation test should be performed next. A baseline ACTH level is obtained, IV ACTH is administered, then cortisol levels are measured 30 and 60 minutes later. If the test is normal, other diagnoses should be considered. Low ACTH and cortisol levels are consistent with secondary or tertiary adrenal insufficiency (due to pituitary or hypothalamic disease, respectively). A low cortisol and high ACTH indicates primary adrenal insufficiency, and the cause should be explored by measuring 21-hydroxylase antibodies to evaluate for autoimmune disease and obtaining a CT scan of the adrenal glands to assess for other causes. An acute adrenal crisis should be treated with rapid IV volume repletion, IV hydrocortisone, and supportive care. Chronic adrenal insufficiency is managed with lifelong oral replacement of glucocorticoids (hydrocortisone or prednisone) and mineralocorticoids (fludrocortisone), with an increased stress-dose of glucocorticoids during illness and prior to surgical procedures. Women may benefit from DHEA supplementation to improve mood, libido, and general well-being.

Although they are part of the diagnostic approach, 21-hydroxylase antibody level (A), cosyntropin stimulation test (B), and CT scan of the adrenal glands (C) would not be the initial step in diagnosis.