Diagnostic accuracy of increased urinary cortisol/cortisone ratio to differentiate ACTH dependent Cushing's syndrome

Abstract

Background and aim

Differential diagnosis between Cushing's Disease (CD) and Ectopic ACTH Syndrome (EAS) may be a pitfall for endocrinologists. The increasing use in clinical practice of chromatography and mass spectrometry improves the measurement of urinary free cortisol (UFF) and cortisone (UFE). We have recently observed that cortisol to cortisone ratio (FEr) was higher in a small series of EAS; in this paper we collected a larger number of ACTH-dependent CS to study the role of FEr to characterize the source of corticotropin secretion.

Materials and methods

High-pressure liquid chromatography with UV detection (HPLC-UV, n=35) or liquid chromatography tandem mass spectrometry (LC-MS/MS, n=72) were used to measure UFF, UFE and FEr in 83 patients with CD and 24 with EAS.

Results

UFF, UFE and FEr levels were higher in EAS than in CD (UFF: 6671 vs 549 nmol/24h; UFE: 2069 vs 464 nmol/24h; FEr: 4.13 vs 0.97; all p<0.001). FEr >1.15 (the best ROC-based threshold) was able to distinguish CD from EAS with 75% sensitivity (SE) and 75% specificity (SP), AUC 0.811; results were similar between HPLC-UV (SE 73%, SP 79%, AUC 0.708) and LC-MS/MS (SE 77%, SP 73%, AUC 0.834; p=0.727). The diagnostic accuracy of FEr was similar to that of CRH test or high dose dexamethasone suppression test (respectively p=0.171 and p=0.683), also combined. Finally, FEr was able to increase the number of correct diagnosis in patients with discordant dynamic tests.

Conclusions

Urinary FEr >1.15 was able to suggest EAS, with a diagnostic accuracy similar to that of other dynamic tests proposed to study ACTH-dependent CS.

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