Development and Validation of a 0.5 mg Dexamethasone Suppression Test as an Initial Screening Test for the Diagnosis of ACTH-dependent Cushing's Syndrome

For the diagnosis of Cushing's syndrome (CS), the overnight 1 mg dexamethasone suppression test (DST) has been widely used as a standard low-dose DST. However, it is evident that I mg DST may not be sensitive enough to detect CS when the cortisol cut-off concentration is 5 mu g/dL. Therefore, we developed and validated 0.5 mg DST as a new screening method for diagnosis of ACTH-dependent CS. To compare 0.5 mg DST with 1 mg DST, 110 patients with ACTH-dependent CS were enrolled, including 88 with Cushing's disease (CD), 8 with subclinical CD and 14 with ectopic ACTH syndrome, as well as 134 control subjects. Subjects were given either 0.5 mg or 1 mg dexamethasone orally at 23:00 on different days, with blood samples collected the following morning between 8:00 and 9:00 to determine plasma cortisol concentration. The area under the receiver operator characteristics curve observing the 0.5 mg DST was higher than that of the 1 mg DST. The most sensitive and specific cut-off value of plasma cortisol concentration using 0.5 mg DST was found to be 3.05 mu g/dL with 99.1% sensitivity and 98.4% specificity, identical to the 3 mu g/dL cut-off currently used in the Japanese guideline for diagnosis of subdinical CD. In conclusion, 0.5 mg DST is a sensitive and specific screening test for diagnosis of ACTH-dependent CS. We recommend 0.5 mg DST with a cortisol cut-off concentration of 3 mu g/dL to be used as the initial step in diagnosing ACTH-dependent CS.