Reevaluation of the Combined Dexamethasone Suppression-Corticotropin-Releasing Hormone Test for Differentiation of Mild Cushing’s Disease from Pseudo-Cushing’s Syndrome

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The diagnostic accuracy of the combined dexamethasone suppression test (DST)-CRH test for the differential diagnosis between Cushing's disease (CD) and pseudo-Cushing syndrome (PCS) has recently been debated. Our objective was to reevaluate the performance of the DST-CRH test to differentiate CD from PCS and compare it with that of midnight plasma cortisol measurement. The study took place at three specialized tertiary care university hospitals. Fourteen patients with PCS and 17 patients with CD matched for 24-h urinary free cortisol were retrospectively studied. Diagnosis or exclusion of CD was the main outcome measure. A 55 nmol/liter cortisol concentration after dexamethasone (DST) yielded 94% sensitivity, 86% specificity, and 90% diagnostic accuracy. Using the historical 38 nmol/liter threshold for plasma cortisol 15 min after CRH administration, the DST-CRH test achieved 100% sensitivity, 50% specificity, and 77% diagnostic accuracy. Increasing the threshold to 110 nmol/liter improved the specificity and diagnostic accuracy to 86 and 93.5%, respectively. However, diagnostic accuracy was not significantly different from that of the DST. A midnight plasma cortisol concentration of more than 256 nmol/liter was consistent with the diagnosis of CD with 100% sensitivity, specificity, and diagnostic accuracy. The diagnostic performance of the DST-CRH test for the differential diagnosis between PCS and mild CD was lower than previously reported. Although the specificity of the test is improved using a revised cortisol threshold, its diagnostic accuracy is not better than that of the standard DST. Our study supports the preferential use of the DST and midnight plasma cortisol measurement as first-line diagnostic tests in equivocal cases.