Salivary Diurnal Cortisol Testing for Cushing's Syndrome

Diagnostic Performance and Recommendations

The Endocrine Society recommends late-night salivary cortisol (LNSC) as a highly sensitive and specific screening test for Cushing's syndrome, with sensitivity of 92-100% and specificity of 93-100% 1
LNSC demonstrates excellent diagnostic accuracy for detecting Cushing's syndrome, based on the loss of normal circadian nadir of cortisol secretion in patients with Cushing's syndrome 1
At least two or three LNSC measurements are recommended to account for variability and potential cyclic hypercortisolism 1
Sampling should occur at the patient's usual bedtime rather than strictly at midnight, as cortisol nadir is tightly entrained to sleep onset 1

Salivary cortisol represents unbound (free) cortisol, which is the biologically active fraction 2
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) provides superior sensitivity and can detect both cortisol and cortisone, avoiding contamination from topical hydrocortisone 1

For critical illness-related corticosteroid insufficiency (CIRCI), salivary cortisol testing is NOT recommended over serum cortisol testing 2
Patients must avoid night-shift work, disrupted sleep-wake cycles, vigorous exercise, food consumption, alcohol, and topical hydrocortisone preparations to ensure accurate results 1

Provide patients with specific instructions to avoid vigorous physical activity, eating, and alcohol before collection, and to collect samples at usual bedtime 1
Obtain at least 2-3 samples on different nights to detect cyclic hypercortisolism 4
If LNSC is mildly elevated, consider mild Cushing's syndrome and repeat testing with additional confirmatory tests 1