Overnight urinary free cortisol determination: a screening test for the diagnosis of Cushing's syndrome

The collection of urine over 24 h to measure free cortisol (UFC) is used to diagnose Cushing's syndrome. However, a complete collection of urine is not easy to achieve and the sampling is frequently inaccurate, so a 24 h collection for the determination of UFC excretion is used as a confirmatory rather than a screening test for Cushing's syndrome. Our objective was to evaluate a more convenient urine collection for screening patients suspected of Cushing's syndrome.

We have studied the possibility of using night-time (from 2000 h to 0800 h) UFC excretion as a screening test for Cushing's syndrome ('overnight UFC').

Thirty patients with proven Cushing's syndrome were studied before treatment (21 cases of Cushing's disease, two cases of ectopic ACTH secretion, seven of adrenal adenoma). The results were compared to those from 150 control obese subjects.

Overnight UFC, and creatininuria (UC), were evaluated at least once in the patients and in all subjects. The 24 h-UFC and UC were determined at least once in the patients and in 56 control subjects.

The overnight UFC/UC ratio clearly separated all but one patient of the two groups: 194 +/- 386 vs 5.7 +/- 3.4 nmol/mumol (P < 0.0005) (ranges 16.2-2024 vs 0.6-17.4, Cushing's syndrome vs controls, respectively). The only patient with Cushing's syndrome who had an overnight UFC/UC ratio that overlapped with that of controls suffered from renal failure. The 24 h UFC/UC ratio of the patients differed from the ratio of controls: 184 +/- 365 vs 8.4 +/- 4.1 nmol/mumol (P < 0.0005) (ranges 14-1639 vs 1.5-21.2, respectively). Four patients with Cushing's syndrome had 24 h UFC/UC ratios lower than the upper control ratio.

The overnight urinary sampling is a simple procedure compared to the 24 h urine collection performed in out-patients. For a sensitivity set at 100%, the specificities were 97% for the overnight UFC/UC ratio and 87% for the 24 h-UFC/UC ratio. This therefore appears to provide a good screening method for Cushing's syndrome.