Significantly high level of late‐night free cortisol to creatinine ratio in urine specimen in patients with subclinical Cushing's syndrome

Abstract

Absence of a late-night cortisol nadir is a consistent biochemical abnormality in patients with cortisol-producing adenoma. We evaluated the abnormality of late-night urinary free cortisol to creatinine ratio (late-night UFCCR) in patients with subclinical Cushing's syndrome (SCS). Fifty-eight patients with incidentally detected adrenocortical adenomas [SCS: 9; nonfunctioning adenoma (NF): 49] were enrolled as subjects. Values measured in all patients were urinary free cortisol accumulated between 9:00 p.m. and 11:00 p.m. (late-night UFCCR), serum cortisol at 11:00 p.m. (midnight serum cortisol: MSC), serum cortisol after 1-mg overnight dexamethasone suppression test (1mg-DST) and 24-h urinary free cortisol (UFC). Median late-night UFCCR value in SCS was significantly higher than that in NF (P<0·001). Significant correlations were observed between late-night UFCCR and each of serum cortisol after 1mg-DST and MSC (r=0·537, P<0·001 and r=0·556, P<0·001, respectively). There was no significant correlation between serum cortisol after 1mg-DST and 24-h UFC (r=0·211, P=0·112). In receiver operating characteristic analysis for diagnosis of SCS, the areas under the curves of late-night UFCCR and 24-h UFC were 0·937 (95% confidence interval 0·865-1·008) and 0·726 (0·874-0·999), respectively. Late-night UFCCR cut-off value of 4·9nmol/μmolCre showed a sensitivity of 100% and a specificity of 76·6%. Patients with SCS showed higher late-night UFCCR values than those with NF. Late-night UFCCR was significantly correlated with autonomous cortisol production findings. Diagnostic performance of late-night UFCCR was superior to 24-h UFC. These results suggest that late-night UFCCR might represent one of the simple and reliable tests for SCS diagnosis.