Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (1076 page)

   The utilization of the metyrapone test has become less frequent as a result of the larger availability of plasma ACTH assays. The limited accessibility to metyrapone in certain countries, as well as the limited number of clinical laboratories who have maintained the urinary 17-hydroxycorticosteroid (17-OHCS) and serum 11-deoxycortisol tests, have also further limited the use of the metyrapone test.

   Metyrapone blocks the conversion of 11-deoxycortisol to cortisol by CYP11B1 (11-beta-hydroxylase, P-450c11), the last step in the synthesis of cortisol. It induces a rapid fall of cortisol and an increase of 11-deoxycortisol in serum.

   The metyrapone test can be performed as an overnight single-dose test or as a 2- or 3-day test. It cannot be performed in a patient who is taking any glucocorticoid.

   The 2-day test is used primarily in the differential diagnosis of hypercortisolism.

   The 2-day test is a slight variation on the standard 3-day test: 24-hour urine and 8
AM
blood specimens are collected during and at the end of a baseline day and during and at the end of the day during which the patient takes 750 mg of metyrapone by mouth every 4 hours for six doses.

   Urinary 17-OHCS excretion and serum 11-deoxycortisol are measured.

   The 3-day test is used mainly for the evaluation of adrenal insufficiency.

   The 3-day test is begun by obtaining a baseline 24-hour urine collection. Immediately after completing this collection, the patient begins taking metyrapone (750 mg orally every 4 hours for six doses) with a glass of milk or a small snack to minimize GI symptoms.

   Subsequent 24-hour urine specimens are collected the day of and the day after metyrapone administration for measurement of urinary 17-OHCS and creatinine excretion. Serum 11-deoxycortisol, cortisol, and plasma ACTH can also be measured 4 hours after the last dose of metyrapone.

   The single-dose overnight test can be used for both indications.

   The single-dose test is performed by oral administration of metyrapone (30 mg/kg body weight, or 2 g for <70 kg, 2.5 g for 70–90 kg, and 3 g for >90 kg body weight) at midnight with a glass of milk or a small snack.

   Serum 11-deoxycortisol and cortisol are measured between 7:30 and 9:30
AM
the next morning; plasma ACTH can also be measured.