The diagnosis of Cushing's syndrome requires demonstration of increased cortisol production and abnormal cortisol suppression in response to dexamethasone. For initial screening, measurement of 24-h urinary free cortisol, the 1-mg overnight dexamethasone test [8:00 A.M. plasma cortisol <1.8 µg/dL (50 nmol/L)], or late-night salivary cortisol measurement is appropriate. Repeat testing or performance of more than one screening test may be required. Definitive diagnosis is established in equivocal cases by inadequate suppression of urinary cortisol [<10 µg/d (25 nmol/d)] or plasma cortisol [<5 µg/dL (140 nmol/L)] after 0.5 mg dexamethasone every 6 h for 48 h. Once the diagnosis of Cushing's syndrome is established, further biochemical testing is required to localize the source. This evaluation is best performed by an experienced endocrinologist. Low levels of plasma ACTH levels suggest an adrenal adenoma or carcinoma; inappropriately normal or high plasma ACTH levels suggest a pituitary or ectopic source. In 95% of ACTH-producing pituitary microadenomas, cortisol production is suppressed by high-dose dexamethasone (2 mg every 6 h for 48 h). MRI of the pituitary should be obtained but may not reveal a microadenoma because these tumors are typically very small. Furthermore, because up to 10% of ectopic sources of ACTH may also suppress after high-dose dexamethasone testing, inferior petrosal sinus sampling may be required to distinguish pituitary from peripheral sources of ACTH. Testing with corticotropin-releasing hormone (CRH) also may be helpful in determining the source of ACTH. Imaging of the chest and abdomen is required to localize the source of ectopic ACTH production; small bronchial carcinoids may escape detection by conventional CT. Pts with chronic alcoholism, depression, or obesity may have false-positive results in testing for Cushing's syndrome—a condition named pseudo-Cushing's syndrome. Similarly, pts with acute illness may have abnormal laboratory test results, since major stress alters the normal regulation of ACTH secretion. The management of Cushing's syndrome is summarized in Fig. 171-1.