Differential diagnosis of Cushing's syndrome

The accurate differential diagnosis of Cushing's syndrome is essential for appropriate and effective treatment. The initial step in the differential diagnosis of Cushing's syndrome is to distinguish between adrenocorticotropic hormone (ACTH)dependent Cushing's syndrome (pituitary or nonpituitary ACTH secreting neoplasm) and ACTH-independent hypercortisolism (due to a functioning adrenal neoplasm, autonomous bilateral adrenal nodular hyperplasia, or factitious/iatrogenic Cushing's syndrome). The measurement of plasma ACTH (immunometric assay) and its response to corticotropin-releasing hormone (CRH) will reliably distinguish ACTH-dependent from ACTH-independent Cushing's syndrome. A common sense approach, considering the patient's age and sex, duration of symptoms, and plasma potassium, ACTH, and urine free cortisol levels, will provide an accurate diagnosis in most. The high-dose dexamethasone suppression test (DST) has no incremental value in the differential diagnosis of Cushing's syndrome and an accuracy of only 80%. Although DST provides great theater, it should be abandoned. Pituitary magnetic resonance imaging (MRI) scans are positive in 25 to 45% of patients with Cushing's disease and in 10 to 15% of patients with ectopic ACTH. If the clinical features suggest pituitary Cushing's, an unequivocally positive MRI scan has good predictive value. The peripheral CRH stimulation test demonstrates a blunted ACTH response to CRH (<35% of basal) in most patients with ectopic ACTH; however, the probability of Cushing's disease is high at all levels of response. Finally, inferior petrosal sinus sampling with CRH stimulation has emerged as the most reliable study in the differential diagnosis of ACTH-dependent Cushing's syndrome.