Diagnosing Adrenal Disorders with Salivary Cortisol

Diagnostic Considerations

The Society of Critical Care Medicine and European Society of Intensive Care Medicine recommend against using salivary cortisol for diagnosing critical illness-related corticosteroid insufficiency due to limited evidence and practical challenges (conditional recommendation, very low quality of evidence) 1, 2, 3
Late-night salivary cortisol is a well-established screening test for Cushing's syndrome with sensitivity and specificity exceeding 90% 4
At least 2-3 late-night salivary cortisol samples are recommended for diagnosis of Cushing's syndrome 4
The American College of Endocrinology or similar organizations may recommend late-night salivary cortisol testing for Cushing's syndrome, which exploits the loss of normal circadian cortisol rhythm in Cushing's syndrome 4

Salivary cortisol levels can be affected by demographic variables such as gender and age 1, 2, 3
Collection variables like time and site of sampling, and saliva volume can impact salivary cortisol levels 1, 2, 3
Practical collection issues, including insufficient saliva or blood contamination, can limit the use of salivary cortisol testing 1, 2, 3

Studies comparing salivary cortisol to serum cortisol show inconsistent results, with some finding strong correlations and others finding no significant difference 1, 2, 3
No study has demonstrated that using salivary cortisol to diagnose adrenal disorders leads to improved patient outcomes 1, 2, 3

For Cushing's syndrome screening, late-night salivary cortisol should be collected at usual bedtime rather than at fixed midnight time 4
For adrenal insufficiency diagnosis, serum total cortisol remains the standard approach, and the high-dose (250-μg) ACTH stimulation test is recommended over low-dose testing 1, 2, 3, 5

The Endocrine Society recommends confirming adrenal insufficiency with serum cortisol testing and ACTH stimulation testing, as salivary cortisol alone is not definitive 6

Salivary cortisol measurements show low values, with morning and evening measurements on Day 1 being 0.10 µg/dL and 0.04 µg/dL, respectively, and late morning and evening measurements on Day 2 being 0.09 µg/dL and 0.08 µg/dL, which are below the expected normal ranges 6

The pattern of low cortisol production across all time points suggests inadequate cortisol response, which would be seen in primary or secondary adrenal insufficiency 6
The American Association of Clinical Endocrinologists recommends proceeding with confirmatory serum testing immediately, as salivary cortisol alone cannot definitively diagnose adrenal insufficiency 6

No specific guidelines are provided with associated citations for required confirmatory testing.

In cirrhotic patients, baseline salivary cortisol <0.18 µg/dL suggests relative adrenal insufficiency, which matches the patient's values, according to the European Association for the Study of the Liver 7, 8

Patients with confirmed adrenal insufficiency require immediate glucocorticoid replacement to prevent adrenal crisis, and empiric hydrocortisone should be considered if the patient is acutely ill, according to the Society of Critical Care Medicine 7, 8