Which test helps differentiate pituitary from ectopic ACTH production in suspected Cushing syndrome?

• A. High-dose dexamethasone suppression test or CRH stimulation; pituitary sources often suppress with high-dose dex.
• B. Low-dose dexamethasone suppression test.
• C. Insulin tolerance test.
• D. ACTH stimulation test.

Answer: (A)

In suspected Cushing syndrome where the ACTH source is in question, tests that probe how the ACTH-secreting tissue responds to glucocorticoid feedback or to CRH are most informative. A high-dose dexamethasone suppression test can reveal whether cortisol production remains suppressible when a strong glucocorticoid signal is present. Pituitary-driven ACTH production (Cushing disease) is often partially suppressible with high-dose dexamethasone, so cortisol falls. Ectopic ACTH sources, from tumors outside the pituitary, usually resist suppression and continue to drive high cortisol levels. The CRH stimulation test adds confirmation: pituitary sources typically show an increase in ACTH (and cortisol) in response to CRH, while ectopic sources often do not respond.

The other tests don’t differentiate the source as reliably. The low-dose dexamethasone test is used to screen for Cushing syndrome but isn’t good at distinguishing pituitary from ectopic sources. The insulin tolerance test and the ACTH stimulation test assess other aspects of pituitary-adrenal function or adrenal responsiveness, not the origin of ACTH production.