The availability of CRH for clinical use and the data so far generated by clinical investigators interested in its application to the problem of
Cushing's syndrome have resulted in a new approach to the differential diagnosis of
Cushing's syndrome (Fig. 2). Once the diagnosis of
Cushing's syndrome is made with certainty, an initial separation into
ACTH-dependent versus
ACTH-independent categories is made on the basis of the plasma
ACTH response to CRH. Plasma
ACTH levels in excess of 10 pg/mL imply an
ACTH-dependent process. Patients with an
ACTH-dependent process are then divided into eutopic versus ectopic sources on the basis of the central to peripheral gradient of
ACTH measured in the inferior petrosal sinuses simultaneously 3 to 5 minutes after the administration of CRH, 1 microgram/kg. The average post-CRH gradient in patients with eutopic
ACTH-dependent
Cushing's syndrome is 50. The lower bound is 3.3. Ectopic sources have a gradient of less than 2. Patients with
ACTH-independent
Cushing's syndrome can be confidently evaluated with imaging techniques, such as CT or MRI, looking for
adrenal neoplasm or the "normal to small" glands characteristic of micronodular adrenal dysplasia.