Lack of suppression with both low- and high-dose dexamethasone in a hypercortisolism workup most strongly suggests a source of cortisol excess from which origin?

• A. Pituitary adenoma
• B. Ectopic ACTH
• C. Adrenal tumor
• D. Addison

Answer: (C)

Dexamethasone suppression testing helps distinguish ACTH-dependent from ACTH-independent Cushing syndrome by showing how cortisol responds to glucocorticoid feedback. If cortisol remains high with low-dose dexamethasone, the picture is Cushing syndrome; if high-dose dexamethasone still fails to suppress cortisol, the source is not pituitary ACTH–driven. In pituitary disease, high-dose dexamethasone often lowers cortisol because the pituitary lesion is partially responsive to feedback. But autonomous adrenal cortisol production or ectopic ACTH production typically shows little to no suppression with either dose. When there is lack of suppression with both low- and high-dose dexamethasone, the most likely origin is an adrenal tumor producing cortisol independently of ACTH. Addison disease isn’t a source of hypercortisolism.