Differential Diagnosis of Cushing’s Syndrome

Abstract

Determining the cause of spontaneous Cushing’s syndrome is essential so that appropriate therapy can be recommended. Most patients (80%) have an ACTH-secreting neoplasm (pituitary or ectopic), while the rest have an adrenal-dependent (ACTH-independent) etiology. After hypercortisolism has been convincingly established, plasma adrenocorticotropic hormone (ACTH) levels are obtained to subdivide Cushing’s syndrome into ACTH-dependent (>20 pg/ml) or ACTH-independent (<5 pg/ml) categories. Corticotropin-releasing hormone (CRH) stimulation testing can help to define these categories when ACTH levels are equivocal (5–20 pg/ml). Since clinical features are unreliable in distinguishing between subtypes of ACTH-dependent and ACTH-independent Cushing’s syndrome, additional biochemical, radiologic, and angiographic tests are needed. Diagnostic accuracy of high-dose dexamethasone suppression testing and CRH stimulation testing are poor when trying to refine the diagnosis of ACTH-dependent Cushing’s syndrome. Bilateral inferior petrosal sinus ACTH sampling with CRH stimulation has become the gold standard in this setting and should be used when magnetic resonance images of the pituitary do not reveal an unequivocal pituitary abnormality in a patient with clinical and biochemical findings consistent with ACTH-dependent Cushing’s syndrome. In patients with ACTH-independent Cushing’s syndrome, computed tomography of the adrenal glands is performed and will demonstrate either a single nodule (benign or malignant) or bilateral nodular hyperplasia caused by several unique pathophysiological mechanisms.