Metyrapone, an 11‑beta hydroxylase inhibitor, causes a fall in cortisol production followed by an increase in ACTH and 11‑deoxycortisol output if the hypothalamic‑pituitary‑adrenal circuit is intact. The test begins by measuring baseline serum cortisol and plasma 11‑deoxycortisol levels at 0800. Three grams of metyrapone are administered at 2300 hours that evening, and then serum cortisol and plasma 11‑deoxycortisol are measured at 0800 the next morning.

Serum cortisol levels, which are usually elevated in patients with Cushing's Syndrome, fall to less than 7 ug/dL the morning after the metyrapone is administered. The test is not valid if the cortisol levels do not fall. Failure to respond to metyrapone with a rise in 11‑deoxycortisol will usually identify the patient with pituitary or hypothalamic disease and secondary adrenal cortical insufficiency. Patients with pituitary tumors should have a normal 11‑deoxycortisol the morning after taking the metyrapone. Patients with an adrenocortical tumor or ectopic production of ACTH will have suppressed 11‑deoxycortisol levels. The metyrapone test has a sensitivity and specificity approaching 100% for distinguishing between pituitary adenoma and adrenocortical tumors. The test is not universally useful for differentiating between pituitary adenoma and ectopic production of ACTH.

Specimen requirement for serum cortisol is one SST tube of blood. The specimen requirement for 11-deoxycortisol is one green top (heparin) tube of blood.


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