A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 26-year-old woman comes to the physician because of fatigue, weight loss, and muscle aches during the past 2 months. There is no personal or family history of serious illness. Her only medication is a multivitamin. A metyrapone stimulation test is performed and the results rule out a diagnosis of adrenal insufficiency. Which of the following changes in laboratory findings are most likely to have been observed in this patient following the administration of the drug?
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A
Increase in serum ACTHCorrect. With normal HPA function, blocking 11-beta-hydroxylase drops cortisol, removing feedback inhibition, so ACTH rises.
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B
Decrease in urinary 17-hydroxycorticosteroidsIncorrect. An intact response causes INCREASED urinary 17-hydroxycorticosteroids (from accumulated 11-deoxycortisol metabolites), not a decrease.
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C
Decrease in serum 11-deoxycortisolIncorrect. 11-deoxycortisol INCREASES because the block is just upstream of cortisol — substrate accumulates rather than depleting.
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D
Increase in serum cortisolIncorrect. Cortisol DECREASES (that's the point of the block); a rise in cortisol would mean the drug didn't work.
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E
Decrease in plasma renin activityIncorrect. Metyrapone blocks 11-beta-hydroxylase in the cortisol pathway and does not directly affect renin secretion, which is governed by renal perfusion and sympathetic tone.
↑ Tap an answer to reveal the reasoning
Answer: A. Metyrapone is an 11-beta-hydroxylase inhibitor — it blocks the final step of cortisol synthesis (conversion of 11-deoxycortisol to cortisol). In a person with an intact HPA axis, blocking cortisol synthesis removes negative feedback on the hypothalamus and pituitary, causing serum ACTH to rise sharply. The rise in ACTH then drives steroidogenesis up to the blocked step, accumulating 11-deoxycortisol (which spills into urine as 17-hydroxycorticosteroids).
Thus a normal/intact response to metyrapone is: increased ACTH, increased 11-deoxycortisol, increased urinary 17-hydroxycorticosteroids, and decreased cortisol. The question states that the test 'rules out' adrenal insufficiency — meaning the response was normal. Therefore an increase in serum ACTH is the expected finding.
In primary or secondary adrenal insufficiency, ACTH fails to rise appropriately (in secondary) or cortisol/11-deoxycortisol fail to respond (in primary). Metyrapone testing has been largely replaced by ACTH stimulation and CRH testing in modern practice, but the physiology remains high-yield.
**Why each option:**
**A.** Correct. With normal HPA function, blocking 11-beta-hydroxylase drops cortisol, removing feedback inhibition, so ACTH rises.
**B.** An intact response causes INCREASED urinary 17-hydroxycorticosteroids (from accumulated 11-deoxycortisol metabolites), not a decrease.
**C.** 11-deoxycortisol INCREASES because the block is just upstream of cortisol — substrate accumulates rather than depleting.
**D.** Cortisol DECREASES (that's the point of the block); a rise in cortisol would mean the drug didn't work.