Is evaluation of cortisol after the dexamethasone suppression test enough? Analysis of the steroid profile after the dexamethasone suppression test using tandem mass spectrometry

Introduction The overnight dexamethasone suppression test (DST) is recommended for the initial testing of Cushing's syndrome. Simultaneous measurement of dexamethasone and cortisol is recommended. This study aimed to determine the cutoff value for dexamethasone measured in DST analysed via liquid chromatography tandem mass spectrometry (2D-LC-MS/MS), and to assess whether analysis of other adrenal steroids than cortisol may improve diagnostic accuracy. Methods A prospective study was conducted including patients with adrenal incidentalomas (n=55), pituitary incidentalomas and symptoms of Cushing's disease (n=18), and healthy controls (n=100) undergoing DST. Plasma levels of ten steroids and dexamethasone were determined via 2D-LC-MS/MS, while cortisol levels were also determined via a chemiluminescence immunoassay. Results The lower 2.5 th percentile of plasma dexamethasone in the control group (cortisol level ˂50 nmol/l) was 3.48 nmol/l, which was set as the cutoff. In the subgroup of patients with adrenal incidentalomas, regardless of the results of DST, subjects exhibited identical changes in the basal adrenal steroid profile: increased 11-deoxycortisol; decreased DHEA and DHEAS levels. After 1 mg dexamethasone administration cortisol and cortisone levels increased, while decreased androstenedione and 17-OHP levels were detected. Statistical significant changes were found in the subgroup of patients with pituitary incidentalomas: increased levels of 11-deoxycortisol, plasma cortisol, cortisone and androstenedione were observed only in those with serum cortisol levels >50 nmol/l. Based on the ROC curves, none of the steroid hormones exhibited higher specificity than cortisol. Conclusion Simultaneous measurement of cortisol and dexamethasone increases DST specificity. The cutoff value for dexamethasone was set to 3.48 nmol/l. None of the adrenal steroids in the DST demonstrated increased specificity; thus, a cortisol concentration ˂50 nmol/l remains the gold standard for ruling out Cushing's syndrome.