Overnight Dexamethasone Suppression Test: Enhanced Accuracy With Late-afternoon Cortisol and Morning/Late-afternoon...

The overnight dexamethasone suppression test (ODST) is precise and highly sensitive; however, its specificity ranges from 80% to 90%.

To assess whether late-afternoon overnight dexamethasone suppression (ODS) cortisol and morning/late-afternoon ODS ACTH measurements improve ODST accuracy.

Prospective, single-center study included healthy adults (n = 60), combined oral contraceptive pill (COCP) users (n = 29), chronic kidney disease (CKD, n = 29), treatment-naïve ACTH-dependent Cushing syndrome (A-CS, n = 33), posttreatment Cushing disease in remission (CD-R, n = 23) or persistence (CD-P, n = 31). Participants underwent the standard 1-mg dexamethasone suppression test; blood samples were collected at 8 to 9 Am for cortisol, ACTH, dexamethasone and at 3 to 4 Pm for cortisol and ACTH.

ODS 4 Pm cortisol was significantly lower than 8 Am in healthy adults (P = .003), COCP (P < .001), CKD (P < .001), and CD-R (P = .001), whereas this difference was not significant in treatment-naïve A-CS and CD-P. ODS 8 Am and 4 Pm cortisol (cutoff: 1.8 μg/dL) showed high specificity in healthy adults (95% and 100%), but its specificity was low in COCP (55% and 79%) and CKD (17% and 52%). ODS 8 Am and 4 Pm ACTH (cutoff: 10 pg/mL) showed high specificity in healthy adults (95%, 100%), COCP (100%, 100%), and CKD (96.6%, 100%), with 100% sensitivity for diagnosing A-CS. The diagnostic accuracy of ODS 4 Pm cortisol, ODS 8 Am ACTH, and ODS 4 Pm ACTH in differentiating CD-R from CD-P was 98.1%, 81.5% and 81.5%, respectively.

Late-afternoon cortisol measurement is a novel modification that enhances ODST specificity. ACTH measurement was particularly useful in COCP and CKD. Before widespread integration in clinical practice, further validation is required.