Expanding the use of salivary cortisol as a non-invasive outpatient test in the dynamic evaluation of suspected adrenal insufficiency
Open accessAbstract
Background: Adrenal insufficiency (AI) is potentially life-threatening, and accurate diagnosis is crucial. The first-line diagnostic test, the adrenocorticotrophic hormone (ACTH) stimulation test, measures serum total cortisol. However, this is affected in states of altered albumin or cortisol-binding globulin levels, limiting reliability. Salivary cortisol reflects free bioactive cortisol levels and is a promising alternative. However, few studies are available, and heterogenous methodologies limit applicability. Methods: This study prospectively recruited 42 outpatients undergoing evaluation for AI, excluding participants with altered cortisol-binding states. Serum (immunoassay) and salivary (liquid chromatography tandem mass spectrometry) cortisol levels were sampled at baseline, 30 min, and 60 min following 250 µg synacthen administration. AI was defined as a peak serum cortisol level <500 nmol/L in accordance with guidelines. Results: The study recruited 21 (50%) participants with AI and 21 without AI. There were no significant differences in baseline characteristics, blood pressure, or sodium levels between groups. Following synacthen stimulation, serum and salivary cortisol levels showed good correlation at all timepoints (R2 = 0.74, P < 0.001), at peak levels (R2 = 0.72, P < 0.001), and at 60 min (R2 = 0.72, P < 0.001). A salivary cortisol cut-off of 16.0 nmol/L had a sensitivity of 90.5% and a specificity of 76.2% for the diagnosis of AI. Conclusion: This study demonstrates a good correlation between serum and salivary cortisol levels during the 250 µg synacthen test. A peak salivary cortisol cut-off of 16.0 nmol/L can be used for the diagnosis of AI. It is a less invasive alternative to evaluate patients with suspected AI. Its potential utility in the diagnosis of AI in patients with altered cortisol-binding states should be further studied.
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Salivary samples can be used during the short Synacthen test in the diagnostic work-up for adrenal insufficiency.
“It has previously been shown that salivary samples can be used during the short Synacthen test (SST) in the diagnostic work-up for AI (29-34).”
From Salivary Cortisol and Cortisone Can Circumvent Confounding Effects of Oral Contraceptives in the Short Synacthen Test (2024) · cites this paper as [34]
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Bäcklund, N., Lundstedt, S., Tornevi, A., Wihlbäck, A.-C., Olsson, T., Dahlqvist, P., & Brattsand, G. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad763 · Cited by 13 · see citing works
“It has previously been shown that salivary samples can be used during the short Synacthen test (SST) in the diagnostic work-up for AI (29-34).”
- Authors
- Tan, S. Y. T., Tan, H. C., Zhu, L., Loh, L. M., Lim, D. S. T., Swee, D. S., Chan, Y. L., Lim, H. B., Ling, S. L., Ou, E. J., Teo, W. E., Zhang, X. P., Goh, H. F., & Kek, P. C.
- Affiliations
- Singapore General Hospital (SG)
- Corresponding author
- Tan, Sarah Ying Tse
- Tan, Hong Chang
- Venue
- Endocrine Connections
- Publisher
- Bioscientifica
- Published
- 2023-02-17
- Volume
- 12
- Issue
- 4
- ISSN
- 2049-3614 (ISSN-L)
- PMC
- PMC10083658
- OpenAlex
- W4321172749
- Cited by
- 10
- References
- 62
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 1
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Endocrine Connections (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Keywords
- adrenal insufficiency, salivary cortisol, ACTH stimulation test, serum cortisol, corticosteroid-binding globulin, non-invasive diagnosis, diagnostic thresholds, liquid chromatography-tandem mass spectrometry
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