Metyrapone inhibits 11-beta-hydroxylase, resulting in blockage of the conversion of 11-deoxycortisol (compound S) to cortisol. As cortisol serum levels fall, normal persons show a release of ACTH, which results in a further increase in serum 11-deoxycortisol levels. The test is used to differentiate ACTH-secreting pituitary tumor from adrenal tumors or from paraneoplastic syndromes due to ectopic ACTH secreting tumors. It also can be used to distinguish normal persons from patients with secondary adrenal insufficiency, but it will not differentiate primary from secondary adrenal insufficiency. A normal hypothalamic-pituitary axis is needed for a normal response.


Patient Preparation:

(1) Before testing the patient, a normal response to exogenous ACTH should be demonstrated, in order to reduce the risk of adrenal crisis in patients with primary adrenal insufficiency.

(2) The single dose test can be performed on outpatients, but the patient should be monitored during testing.

(3) Usually the dose of metyrapone is given at midnight with specimen collection occurring the following morning.

(4) metyrapone 30 mg/kg (maximum dose 3 grams) is given orally at 11 PM to midnight. Since metyrapone can cause gastric irritation, mild or a light snack is given with the oral dose; this also helps delay metyrapone absorption.


Specimen Collection: A baseline serum sample is collected prior to metyrapone administration. A serum sample is collected at 8 AM the following morning.


Testing: The serum is tested for 11-deoxycortisol, cortisol and ACTH.


Relative Contraindications: In patients with possible primary adrenal insufficiency, this test can precipitate adrenal crisis. The test should be performed with caution in such patients. All patients should be monitored during testing, with supportive measures and cortisone replacement therapy initiated if adrenal crisis should develop.



• normal persons show increased 11-deoxycortisol levels (> 7 µg/dL, normally <= 1 µg/dL), reduced cortisol (< 3 µg/dL) and increased ACTH (> 150 pg/mL).

• Patients with hypopituitarism, Cushing's disease due to adrenal tumors or nonendocrine tumors secreting ACTH will have no response or an impaired response to the metyrapone

• A reduced response is seen in drug therapy with drugs that increase hepatic metyrapone metabolism (phenytoin, phenobarbital) or with steroid therapy (glucocorticoids, oral contraceptives, estrogens)

• An exaggerated response can be seen in pituitary ACTH secreting adenomas (pituitary Cushing's disease)


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