Concomitant Medication Use Can Confound Interpretation of the Combined Dexamethasone-Corticotropin Releasing Hormone Test in Cushing’s Syndrome

Abstract

The ability of combined dexamethasone-corticotropin releasing hormone (Dex-CRH) testing to distinguish pseudo-Cushing's syndrome (PCS) from Cushing's syndrome is controversial. One factor potentially impairing diagnostic efficacy is the concomitant use of commonly prescribed medications that may alter dexamethasone metabolism. Our objective was to assess the diagnostic accuracy of the Dex-CRH test and evaluate the potential impact of concomitant drugs. The study was a retrospective one. Participants included 101 patients [60 Cushing's disease (CD); 41 PCS] who underwent 112 Dex-CRH tests. Patients were divided into two groups, depending on use of medications potentially interfering with dexamethasone metabolism: 58 tests were classified as No Meds (32 CD; 26 PCS) and 54 as Meds (34 CD; 20 PCS). The latter group was further subdivided into patients taking one medication vs. those taking multiple medications. Diagnostic accuracy of different serum cortisol and ACTH thresholds at baseline and 15 min after CRH injection was assessed. The specificity of a baseline post-low-dose-dexamethasone-suppressed test cortisol lower than 1.4 microg/dl (38 nmol/liter) was significantly higher in the No Meds vs. the Meds group (P = 0.014). Sensitivity and specificity using a post-CRH cortisol cutoff of 1.4 microg/dl (38 nmol/liter) were 93.1% (95% confidence interval = 88.4-97.8) and 92.3% (95% confidence interval = 87-97.6) in the No Meds group. The specificity of a cortisol lower than 1.4 microg/dl (38 nmol/l) at 15 min after CRH was significantly higher in patients taking only one medication vs. those on multidrug treatment (P < 0.05). Medications commonly prescribed in hypercortisolemic patients undergoing Dex-CRH testing may contribute to the variable diagnostic accuracy of this test. Prospective studies to address this issue are needed.