If a high-dose dexamethasone suppression test results in cortisol suppression, which source of ACTH is more likely?

• A. Pituitary source
• B. Ectopic source
• C. Adrenal tumor
• D. No ACTH involvement

Answer: (A)

High-dose dexamethasone suppression works because dexamethasone provides strong negative feedback on the pituitary. If cortisol levels fall after giving a high dose, it means the ACTH driving cortisol production is coming from the pituitary and remains responsive to glucocorticoid feedback—this is characteristic of Cushing disease. In contrast, ectopic ACTH production comes from non-pituitary sources and is not suppressed by glucocorticoids, so cortisol stays high. Adrenal tumors can produce cortisol independently of ACTH, and even with high-dose dexamethasone, cortisol often remains elevated because the tumor isn’t governed by pituitary feedback. So cortisol suppression with high-dose dexamethasone points to a pituitary source of ACTH.