Which finding would most strongly indicate a pituitary source of ACTH in suspected Cushing syndrome?

• A. Low ACTH with cortisol elevation
• B. Normal ACTH with cortisol elevation
• C. Elevated ACTH with cortisol suppression on high-dose dexamethasone
• D. Elevated cortisol that does not suppress with high-dose dexamethasone

Answer: (C)

The key idea is using ACTH testing to tell apart ACTH-dependent sources of Cushing syndrome and then using a high-dose dexamethasone test to localize to the pituitary. When cortisol is high and ACTH is elevated (or inappropriately normal) in this setting, a pituitary origin is suspected. In that scenario, giving a high dose of dexamethasone often suppresses cortisol production because the pituitary adenoma still retains some feedback sensitivity to glucocorticoids. This suppression pattern is what points toward a pituitary source. If cortisol stays high despite the high-dose dexamethasone, it suggests ectopic ACTH production rather than a pituitary tumor. So the combination of elevated ACTH with cortisol suppression on a high-dose dexamethasone test most strongly indicates a pituitary source.