The evaluation of ACTH-dependent Cushing's syndrome

The causes of endogenous Cushing's syndrome include primary excess ACTH production (ACTH-dependent forms) and primary adrenal cortisol production. Because hypercortisolism suppresses normal ACTH secretion, ACTH levels are low in the primary adrenal forms and are normal or increased in patients with ACTH-dependent Cushing's syndrome. Excess ACTH production by a pituitary corticotrope tumor, termed Cushing's disease, is more common (80%) than nonpituitary, or "ectopic", ACTH secretion (20%). Most patients with ectopic ACTH secretion cannot be differentiated clinically from those with Cushing's disease, so biochemical tests must be used. Inferior petrosal sinus sampling can identify a pituitary source of ACTH because of the increase in petrosal ACTH concentration compared with peripheral blood. This test has near 100% diagnostic accuracy, but it is costly and invasive. The corticotropin-releasing hormone stimulation test and overnight 8 mg dexamethasone suppression test lack these drawbacks, but they have less sensitivity for Cushing's disease (93% and 71%, respectively) when cutpoints that exclude all patients with ectopic ACTH secretion are used. MRI of the pituitary gland reveals a tumor in about 50% of patients with Cushing's disease; conversely, imaging of the chest and abdomen is essential for localizing tumors producing ACTH ectopically.