Screening Tests for Cushing's Syndrome: Urinary Free Cortisol Role Measured by LC-MS/MS

Area of Science:

• Endocrinology
• Clinical Diagnostics
• Biochemistry

Background:

• The Endocrine Society recommends the 1-mg dexamethasone suppression test (DST), late-night salivary cortisol (LNSC), or urinary free cortisol (UFC) for initial Cushing's syndrome (CS) screening.
• Evaluating the diagnostic performance of these initial screening tests is crucial for accurate hypercortisolism diagnosis.

Purpose of the Study:

• To compare the diagnostic accuracy of the 1-mg DST, LNSC, and UFC measurements in patients with suspected Cushing's syndrome.

Main Methods:

• Retrospective analysis of 137 patients with suspected hypercortisolism (38 with CS, 99 without).
• UFC measured by liquid chromatography tandem-mass spectrometry.
• LNSC measured by radioimmunoassay; serum cortisol by chemiluminescence immunoassay.

Main Results:

• Urinary free cortisol (UFC) demonstrated high sensitivity (97%) and specificity (91%) with a cutoff of 170 nmol/24 hours.
• The 1-mg dexamethasone suppression test (DST) showed 100% sensitivity at 50 nmol/L and 97% specificity at 138 nmol/L.
• Late-night salivary cortisol (LNSC) had 84% sensitivity and 89% specificity at 14.46 nmol/L.
• UFC exhibited superior positive and negative likelihood ratios compared to DST and LNSC.
• Receiver-operating curve analysis confirmed UFC's diagnostic power was at least as good as all other combinations of tests.

Conclusions:

• Urinary free cortisol (UFC) measurement using liquid chromatography tandem-mass spectrometry offers the highest accuracy for diagnosing Cushing's syndrome in patients with suspected hypercortisolism.
• UFC is a reliable and effective first-line screening test for CS.