The 4-mg intravenous dexamethasone suppression test in the diagnosis of Cushing's syndrome

OBJECTIVE: Optimal diagnostic criteria for the 4-mg intravenous dexamethasone suppression test (IVDST) in patients with Cushing's syndrome (CS), compared with normal subjects, have not been established. We evaluated the performance of the 4-mg IVDST for differentiating CS from normal subjects and to define the responses in CS of various aetiologies. DESIGN, SUBJECTS, MEASUREMENTS: Thirty-two control subjects [normal and overweight/obese participants with or without type 2 diabetes) were prospectively studied, and data from 66 patients with Cushing's disease (CD), three with ectopic ACTH syndrome (EAS), 14 with adrenal Cushing's (AC)] and 15 with low probability of CS (LPC) from three tertiary hospitals were retrospectively evaluated. Dexamethasone was infused at 1 mg/h for 4 h. Plasma cortisol and ACTH were measured at -60 min (baseline), -5 min, +3 h, +4 h, +5 h and at +23 and +23.5 h on Day 2. RESULTS: Control subjects (including those with type 2 diabetes) exhibited a marked suppression of cortisol which was maintained until Day 2. Two of 15 patients with LPC had Day 2 cortisol results that overlapped with CS. Patients with CD demonstrated partial suppression, with rebound hypercortisolism on Day 2. Patients with AC and EAS did not suppress cortisol levels. Day 2 cortisol level of >130 nmol/l (or >20% of the baseline) diagnosed CS with 100% sensitivity and 96% specificity. CONCLUSION: While the IVDST allowed complete discrimination between control subjects and CS, 13% of LPC overlapped with CS. Given the small number of EAS, no conclusion can be drawn regarding the utility of this test in the differential diagnosis of CS.