In order to diagnose Cushing’s Syndrome in patients with multiple and progressive features compatible with the syndrome or an adrenal incidentaloma, three screening tests are routinely used: urinary cortisol (2x 24 hrs), late night salivary cortisol (2x) and the 1 mg overnight dexamethasone suppression test. The evidence for the cut-off values used for these tests was mainly obtained years ago with now obsolete methods.

The objective of this study was to re-examine the validity of these values using state of the art methods traceable to international reference methods and/or international reference standards.

For this purpose a retrospective cohort study was conducted. Since January 2016 all patients suspected for Cushing’s syndrome were screened using urinary cortisol (LC-MSMS), dexamethasone suppression test and salivary cortisol (CORT II, Roche Diagnostics). Final diagnosis was based on laboratory data, clinical data, radiological data and pathological findings after operation. Using the results extracted from the laboratory information system and the final diagnosis, a ROC-curve was generated and the optimal cut-off values were calculated for each screening test.

A total of 243 patients were screened for Cushing Syndrome. Of these, 22 were diagnosed with Cushing’s Syndrome (laboratory results based on current reference limits and clinical data confirming diagnosis). Since these tests are used for Cushing screening we aim at a 100% sensitivity. The newly calculated cut-off values were: 123 nmol/L for the dexamethasone suppression test (spec. 97.2%), 5.7 nmol/L for the salivary cortisol (spec. 93%) and 101 nmol/L for the urinary cortisol (spec. 73.4%).

Re-evaluation of the cut-of values for Cushing Syndrome screening resulted in a higher cut-off value for the dexamethasone suppression test (was 50 nmol/L) and a lower cut-off value for urinary cortisol (was 150 nmol/L). Discussions regarding specificity at cut-off levels of 50 nmol/L versus 30 nmol/L in the dexamethason suppression test thus seem futile.