To differentiate ACTH-dependent from ACTH-independent Cushing's syndrome after hypercortisolism is established, which tests are used?

To differentiate ACTH-dependent from ACTH-independent Cushing's syndrome after hypercortisolism is established, which tests are used?

• A. Plasma ACTH level and high-dose dexamethasone suppression test
• B. Dexamethasone suppression test alone
• C. Serum cortisol measurement
• D. Urine free cortisol

Answer: (A)

When hypercortisolism is established, the next step is to determine the source of ACTH drive. Measuring plasma ACTH distinguishes ACTH-dependent from ACTH-independent Cushing’s. If ACTH is low, the excess cortisol is coming from the adrenal glands (ACTH-independent). If ACTH is not low, the condition is ACTH-dependent, and the next step is to use a high-dose dexamethasone suppression test to tell pituitary (Cushing disease) from ectopic ACTH production. In pituitary-driven cases, high-dose dexamethasone often suppresses cortisol, whereas in ectopic ACTH syndrome there is little or no suppression. So the combination of plasma ACTH level and a high-dose dexamethasone suppression test best differentiates the sources after confirming hypercortisolism. Dexamethasone suppression tests alone can’t reliably identify the ACTH source, and serum or urine cortisol measurements by themselves show cortisol excess but do not distinguish the underlying cause.

When hypercortisolism is established, the next step is to determine the source of ACTH drive. Measuring plasma ACTH distinguishes ACTH-dependent from ACTH-independent Cushing’s. If ACTH is low, the excess cortisol is coming from the adrenal glands (ACTH-independent). If ACTH is not low, the condition is ACTH-dependent, and the next step is to use a high-dose dexamethasone suppression test to tell pituitary (Cushing disease) from ectopic ACTH production. In pituitary-driven cases, high-dose dexamethasone often suppresses cortisol, whereas in ectopic ACTH syndrome there is little or no suppression. So the combination of plasma ACTH level and a high-dose dexamethasone suppression test best differentiates the sources after confirming hypercortisolism.

Dexamethasone suppression tests alone can’t reliably identify the ACTH source, and serum or urine cortisol measurements by themselves show cortisol excess but do not distinguish the underlying cause.