Yield of Serum Dexamethasone Measurement for Reducing False-Positive Results of Low-Dose Dexamethasone Suppression Testing

Background: The low-dose dexamethasone suppression test (DST) using a cortisol cutoff of 1.8 mu g/dL has approximate sensitivity of 95% and specificity of 80% for detecting Cushing syndrome. False-positive DST results can be caused by a variety of conditions, by low dexamethasone bioavailability, or by failure to take dexamethasone as instructed. In an effort to reduce false positives caused by low bioavailability or medication noncompliance, we evaluated the yield of serum dexamethasone measurement for identifying invalid results. Methods: Data were queried for orders requesting concurrent measurement of serum cortisol and dexamethasone over a 41-month period. Inclusion criteria were serum cortisol and dexamethasone measured from the same specimen, specimen collection before 9 AM after 1mg dexamethasone administration, and results for both analytes documented in the electronic medical record. Seventy paired measurements were identified with these criteria. Results were categorized into 4 groups based on observed cortisol and dexamethasone concentrations: (a) suppressed cortisol, low dexamethasone; (b) suppressed cortisol, therapeutic dexamethasone; (c) unsuppressed cortisol, low dexamethasone; or (d) unsuppressed cortisol, therapeutic dexamethasone. Results: Overall, 35 (50%) results demonstrated suppressed cortisol and therapeutic dexamethasone levels. The next largest group was unsuppressed cortisol and therapeutic dexamethasone, representing approximately 32% (n = 22) of the study population. Ten result sets (14%) fell into the unsuppressed cortisol and low dexamethasone category, and 3 paired measurements (4%) fit the criteria for suppressed cortisol and low dexamethasone. Conclusions: The measurement of serum dexamethasone following DST reduces the false-positive rate associated with subtherapeutic dexamethasone levels. IMPACT STATEMENT Individuals with manifestations suggestive of Cushing syndrome may be screened using the low-dose DST. False-positive suppression test results can lead to unnecessary interventions and avoidable expenses. In this study, we evaluated a proposed approach to reduce false-positive screens using concurrent measurement of serum dexamethasone and cortisol. The data presented verify that serum dexamethasone measurement is a practical and affordable option for reducing false-positive results caused by low dexamethasone bioavailability or noncompliance with medication administration instructions.