Cushing's syndrome is usually caused by the secretion of corticotropin or cortisol by a pituitary or adrenal tumor, respectively, or by ectopic secretion of corticotropin. It is possible to determine the specific abnormality in most patients, but it can sometimes be difficult to decide whether the patient has hypercortisolism and whether it is primary or due to major depressive disorder or to the stress of other diseases. Determining the cause of the hypercortisolism involves performing multiple tests in a logical sequence; the results should all be consistent with the same diagnosis. Treatment should aim to cure the hypercortisolism and to eliminate any tumor that threatens the patient's health, while minimizing the chance of an endocrine deficiency or long-term dependence on medications.