Cushing's syndrome and the nodular adrenal gland

Given the above potential pitfalls in a patient with Cushing's syndrome and an abnormal adrenal gland by CT or MR imaging, what recommendations can be made? A proposed algorithm is shown in Figure 1. A patient with suspected Cushing's syndrome first requires biochemical confirmation of hypercortisolism. This is best accomplished by obtaining an elevated 24-hour urinary free cortisol level; the overnight 1-mg dexamethasone test can also be used but is considerably less sensitive and specific. Once Cushing's syndrome is confirmed, the essential decision is whether the hypercortisolism is ACTH-dependent. Multiple plasma ACTH levels should be measured using a sensitive ACTH assay. If the ACTH levels are 'normal' or moderately elevated (i.e., nonsuppressed), proceed to IPSS and an evaluation for pituitary versus ectopic sources of ACTH. If basal ACTH levels are suppressed, perform a CRH test to ensure that the ACTH cannot be stimulated. If the CRH test is positive, proceed with IPSS. If basal and stimulated ACTH levels are low, perform an adrenal CT with thin cuts. If a single lesion is seen, proceed with unilateral adrenalectomy. Most such lesions will prove to be adenomas, but very rare small adrenal carcinomas can be found. If multiple bilateral lesions are seen, proceed with bilateral adrenalectomy (unless the ACTH status is still unclear). Subjects with MAH need to be followed for the development of Nelson's Syndrome, while subjects with PPNAD need to be evaluated for Carney's complex. If adrenal architecture is unclear on CT scan, other modalities including MR imaging and adrenal vein sampling for cortisol levels may be necessary.