Urine Free Cortisol in the High-Dose Dexamethasone Suppression Test for the Differential Diagnosis of the Cushing Syndrome

Objective: To develop criteria for interpreting the high-dose dexamethasone suppression test using urine free Cortisol as an end point for the differential diagnosis of the Cushing syndrome. Design: Retrospective review. Setting: Inpatient research ward. Patients: Patients (118) with surgically confirmed causes of the Cushing syndrome: 94 with pituitary disease, 14 with primary adrenal disease, and 10 with ectopic adrenocorticotropic hormone (ACTH) secretion. Main Outcome Measures: The sensitivity, specificity, and diagnostic accuracy were determined for the high-dose dexamethasone suppression test using urine free Cortisol and using 17-hydroxysteroid excretion. For each analysis, patients with pituitary disease were considered to be "diseased" and patients with nonpituitary disease were considered to be "non-diseased". The level of suppression that gave 100% specificity was determined for each steroid. Results: The accuracy of urine free Cortisol when used as an end point in the high-dose dexamethasone suppression test was equivalent to that of 17-hydroxysteroid excretion. At all levels of sensitivity and specificity, however, the degree of suppression of urine free Cortisol used for the diagnosis of pituitary disease was greater than that of 17-hydroxysteroid excretion. The likelihood ratios for pituitary disease based on urine free Cortisol suppression of > 50%, of > 80%, and of > 90% were 4.2,10.1, and "infinite," respectively. Suppression of urine free Cortisol greater than 90% or suppression of 17-hydroxysteroid excretion greater than 64% was associated with 100% specificity. When these criteria were combined, the percentage of correct predictions (102 of 118 [86%; 95% Cl, 78% to 92%]) was higher than that obtained using either steroid alone (89 of 118 [75%; Cl, 65% to 83%]) (P = 0.009) and higher than that obtained using the traditional criterion of 50% suppression for 17-hydroxysteroid excretion (95 of 118 [80%; Cl, 71% to 87%]) (P = 0.016). Conclusions: In the high-dose dexamethasone suppression test, the degree of suppression of urine free Cortisol used for the diagnosis of pituitary disease is greater than that traditionally used for 17-hydroxysteroid excretion. The diagnostic performance of the test is improved by measuring both urine free Cortisol and 17-hydroxysteroid excretion and by requiring greater suppression of both steroids.