Context: The diagnostic accuracy of the combined dexamethasone suppression-CRH test (DST-CRH test) for the differential diagnosis between Cushing's disease (CD) and pseudo-Cushing syndrome (PCS) has recently been debated.

Objective: To reevaluate the performance of the DST-CRH test to differentiate CD from PCS and compare it with that of midnight plasma cortisol measurement.

Setting: 3 specialized tertiary care university hospitals.

Design: 14 patients with PCS and 17 patients with CD matched for 24h urinary free cortisol were retrospectively studied.

Main Outcome Measure: diagnosis or exclusion of CD.

Results: A 55 nmol/l cortisol concentration after dexamethasone (DST) yielded 94% sensitivity, 86% specificity and 90% diagnostic accuracy. Using the historical 38 nmol/l threshold for plasma cortisol 15 min following CRH administration, the DST-CRH test achieved 100% sensitivity, 50% specificity and 77% diagnostic accuracy. Increasing the threshold to 110 nmol/l 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 >256 nmol/l was consistent with the diagnosis of CD with 100% sensitivity, specificity and diagnostic accuracy.

Conclusion: 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.