In the metyrapone test, what results indicate a normal HPA axis compared with a deficient axis?

• A. Blocks cortisol synthesis; normal axis increases ACTH and 11-deoxycortisol after metyrapone; deficient axis shows blunted or no increase.
• B. Stimulates cortisol synthesis; normal axis decreases ACTH after metyrapone.
• C. Blocks ACTH release; normal axis cortisol decreases.
• D. Measures aldosterone; normal axis increases aldosterone.

Answer: (A)

The metyrapone test assesses the integrity of the HPA axis by blocking cortisol synthesis and watching the downstream hormonal response. Metyrapone inhibits 11-beta-hydroxylase, so cortisol production drops. In a normal, functioning axis, the pituitary senses the fall in cortisol and increases ACTH. The higher ACTH then drives the adrenal pathway to produce more 11-deoxycortisol, causing both ACTH levels and 11-deoxycortisol levels to rise. If the axis is deficient, whether from pituitary/hypothalamic failure or adrenal failure, the expected increase in ACTH and 11-deoxycortisol is blunted or absent, signaling impaired HPA axis function.