As developed by Liddle and colleagues, the dexamethasone suppression test measures the response of the Porter-Silber chromogens to the exogenous administration of dexamethasone.12 Urine collections are made for 6 days. Basal, or control, collections are made on days 1 and 2 of the test. Dexamethasone is given at a dose of 2 mg per day on days 3 and 4, and 8 mg per day on days 5 and 6. At some point during the test, the excretion of Porter-Silber chromogens is reduced by half in 95% of patients with Cushing disease (Fig. 74-3). It is reduced by less
than half in patients with other causes of Cushing syndrome. The urine free cortisol also can be used as an end point, but must decrease by 80% or more to indicate that suppression has occurred13 (see Chap. 75).

Metyrapone is a competitive inhibitor of the 11-hydroxylase enzyme (Fig. 74-4). It blocks the biosynthesis of cortisol. This leads to a reduced plasma cortisol concentration. If the feedback axis is intact, adrenocorticotropic hormone (ACTH) secretion increases in an attempt to reestablish normal plasma cortisol concentrations. Because large amounts of 11-deoxy-cortisol are produced, 11-deoxycortisol and its metabolites raise the urinary concentration of Porter-Silber chromogens (Fig. 74-5). The traditional rule of thumb is that a doubling of the basal level of Porter-Silber chromogens indicates an intact feedback axis.14