Morning Urinary Cortisol-to-Creatinine Ratio by ECLIA: An Accurate Screen for Cushing Syndrome

Abstract Background In the diagnosis of Cushing syndrome, 24-hour urinary free cortisol (UFC) collection is cumbersome and incomplete collections affect accuracy. The validated liquid chromatography (LCMS-MS) based estimation of UFC is inaccessible in most parts of the world. The morning first-void urinary cortisol–creatinine ratio (UCCR) is convenient for sample collection. This study evaluated the diagnostic accuracy of electrochemiluminescence immunoassay (ECLIA)–based morning first-void UCCR for the diagnosis of Cushing syndrome. Methods Inclusion criteria included either ≥3 clinical features suggestive of CS or ≥1 discriminatory feature with one more feature, or an adrenal incidentaloma. CS diagnosis was confirmed using a gold standard consisting of postoperative histopathology or remission following surgery. All participants underwent measurement of late-night salivary cortisol (LNSC), 24-hour UFC, and morning first-void UCCR using Roche ECLIA platform. Diagnostic performance was assessed using receiver operating characteristic analysis. Results Of 184 patients suspected of CS, 126 completed all study procedures and were included in the final analysis. Thirty-two participants (25.4%) were confirmed to have CS. UCCR showed area under the curve (AUC) of 0.963 (95% CI,0.93–0.99; P < 0.001). At a cutoff of 18.6 nmol/mmol, UCCR showed a sensitivity of 84.4%, specificity of 94.6%, and negative predictive value (NPV) of 94.7%. Diagnostic performance was comparable to 24-hour UFC (AUC 0.95) and LNSC (AUC 0.996). Conclusion ECLIA-based morning first-void UCCR demonstrates excellent diagnostic accuracy for Cushing syndrome, comparable to 24-hour UFC. Together with LNSC it can simplify the screening process for Cushing syndrome and may represent a practical alternative to 24-hour UFC test.