Introduction: Urinary free cortisol (UFC) determination has suboptimal sensitivity (SE) and specificity (SP) especially in mild Cushings syndrome (CS).
Aim: To determine the performance of UFC and its metabolite cortisone (UFE) measured using accurate assays such as HPLC and LCMS/MS in diagnosing patients with CS.
Patients and methods: Sixty-seven patients with CS were compared to 49 sex- and age-matched non-CS. UFF and UFE levels were assessed by HPLC until 2009 and afterwards by LCMS/MS. The mean value of two 24-h urine collections was used for the analysis. SE and SP were calculated at different cut-off values using ROC curve analysis.
Results: UFF and UFE values were significantly higher in patients with CS. However, the diagnostic performance of UFF by HPLC was low with 75.8% SE and 81.1% SP (cut-off value >33.9 μg/24 h). The performance of UFF by LCMS/MS was 88.2% SE and 91.2% SP (cut-off value >47.4 μg/24 h). The performance of UFE was better than UFF by both assays. UFE by LCMS/MS showed 97.1% SE and 91.7 SP% using a cut-off value >88.7 μg/24 h. When CS patients were stratified according to disease severity, UFE by LCMS/MS showed a good diagnostic profile also in mild CS (UFF <2× ULN) with 92.3% SE and 91.7% SP (cut-off value >88.7 μg/24 h). Conversely, the performance of UFF in mild CS was low (84.6% SE and 75% SP; cut-off value >44.2). UFF and UFE showed an optimal diagnostic performance with 100% SE and 100% SP in moderate to severe CS (UFF ≥2× ULN). The performance of urinary steroids was not different according to age, sex, disease aetiology, and disease status in CS.
Conclusions: UFE measured by LCMS/MS seems to be a new and good biomarker in diagnosing CS especially in patients with mild hypercortisolism at higher risk for misdiagnosis with UFF.