Improved methods and systems for differentially diagnosing ACTH-dependent Cushing's syndrome are provided herein. Treatment methods can use glucocorticoid receptor antagonists, which differentially affects the ratio of cortisol to ACTH levels in patients having Cushing's Disease versus patients having Ectopic Cushing's Syndrome. Methods for differentially diagnosing ACTH-dependent Cushing's syndrome can include obtaining baseline cortisol and ACTH levels of a patient, treating the patient with a glucocorticoid receptor antagonist (GRA) according to a protocol that would typically substantially elevate cortisol levels, obtaining post-treatment cortisol and ACTH levels of the patient, determining a differential relationship between baseline cortisol and ACTH levels and post-treatment cortisol and ACTH levels and providing a positive diagnosis based on the differential relationship.
