Diagnostic Accuracy Study of Morning Salivary Cortisone for Screening Adrenal Insufficiency in a Real-World Cohort
Constantinos Televantos, Phillip J Monaghan, Maria Michaelidou, Lillian Ruiheng Chen, Mohammed Ahmed, Jan Hoong Ho, Shaishav Dhage, Claire Higham, Brian Keevil, Safwaan AdamAbstract
Context
Morning serum cortisol is used to screen for adrenal insufficiency, but requires venepuncture, early morning clinic attendance, and may be affected by altered corticosteroid-binding globulin (CBG) levels. Salivary cortisone is a non-invasive, home-based alternative.
Objective
To assess the diagnostic accuracy of morning salivary cortisone for screening adrenal insufficiency and establish clinically relevant thresholds.
Design
Retrospective cross-sectional diagnostic accuracy study (2017 to 2024).
Setting
Single tertiary oncology and endocrinology center in the United Kingdom.
Participants
Consecutive patients undergoing adrenocorticotropin hormone (ACTH) stimulation test for suspected adrenal insufficiency.
Intervention
Salivary sampling for cortisone and cortisol.
Main Outcome Measures
Sensitivity and specificity of baseline salivary cortisone.
Results
A total of 517 ACTH stimulation tests in 449 participants were included; adrenal insufficiency was confirmed in 104 tests (20.1%). Baseline salivary cortisone accurately predicted adrenal insufficiency (area under the receiver operating characteristic curve [AUC] 0.93, 95% CI [0.91–0.95]), similar to serum cortisol (0.93, 0.90–0.95; p = 0.67) and superior to salivary cortisol (0.87, 0.82–0.91; p = 0.00063). A baseline salivary cortisone rule-out threshold ≥703 ng/dL (19.5 nmol/L) (sensitivity 0.97 [95% CI 0.92–0.99]; specificity 0.59 [0.54–0.63]) and a rule-in threshold <180 ng/dL (5.0 nmol/L) (sensitivity 0.58 [0.48–0.67]; specificity 0.97 [0.95–0.98]) provided the highest net benefit. An intermediate threshold <389 ng/dL (10.8 nmol/L) (sensitivity 0.83 [0.74–0.89]; specificity 0.87 [0.83–0.90]) identified patients for whom glucocorticoid cover should be considered while awaiting confirmatory testing.
Conclusion
Baseline morning salivary cortisone performs at least as well as serum cortisol for adrenal insufficiency screening.