A comparison of salivary steroid levels during diagnostic tests for adrenal insufficiency
Open accessAbstract
Numerous diagnostic tests are used to evaluate the hypothalamic-pituitary-adrenal axis (HPA axis). The gold standard is still considered the insulin tolerance test (ITT), but this test has many limitations. Current guidelines therefore recommend the Synacthen test first when an HPA axis insufficiency is suspected. However, the dose of Synacthen that is diagnostically most accurate and sensitive is still a matter of debate. We investigated 15 healthy men with mean/median age 27.4/26 (SD±4.8) years, and mean/median BMI (body mass index) 25.38/24.82 (SD±3.2) kg/m2. All subjects underwent 4 dynamic tests of the HPA axis, specifically 1 μg, 10 μg, and 250 μg Synacthen (ACTH) tests and an ITT. Salivary cortisol, cortisone, pregnenolone, and DHEA (dehydroepiandrosterone) were analysed using liquid chromatography-tandem mass spectrometry. During the ITT maximum salivary cortisol levels over 12.5 nmol/l were found at 60 minutes. Maximum cortisol levels in all of the Synacthen tests were higher than this; however, demonstrating that sufficient stimulation of the adrenal glands was achieved. Cortisone reacted similarly as cortisol, i.e. we did not find any change in the ratio of cortisol to cortisone. Pregnenolone and DHEA were higher during the ITT, and their peaks preceded the cortisol peak. There was no increase of pregnenolone or DHEA in any of the Synacthen tests. We demonstrate that the 10 μg Synacthen dose is sufficient stimulus for testing the HPA axis and is also a safe and cost-effective alternative. This dose also largely eliminates both false negative and false positive results.
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The validity of the calculated lower reference limits for salivary cortisol and cortisone is strengthened by the similarities to previously published cutoffs.
“The validity of our calculated LRLs for salivary cortisol and cortisone is strengthened by the similarities to previously published cutoffs (25, 30, 36, 42).”
From Salivary Cortisol and Cortisone Can Circumvent Confounding Effects of Oral Contraceptives in the Short Synacthen Test (2024) · cites this paper as [30]
The Results report stimulated salivary cortisol and cortisone levels in healthy participants, including values above 12.5 and 27.8 nmol/L during the insulin tolerance test. The paper does not designate these values as calculated lower reference limits or compare them with the citing authors’ limits, so the claimed similarity to published cutoffs is not established by this source alone. (LLM, conf=0.78)
Experimental — accuracy not yet measuredSalivary 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 [30]
The Methods and Results describe collecting saliva during Synacthen tests and measuring a salivary cortisol response. The Discussion says salivary cortisol behaved similarly to serum cortisol, supporting its potential use during testing. But the study included only healthy men, so it did not establish that salivary sampling works in the diagnostic work-up of patients with suspected adrenal insufficiency; the indexed passages provide no page numbers. (LLM, conf=0.82)
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Sorted by citations
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“The validity of our calculated LRLs for salivary cortisol and cortisone is strengthened by the similarities to previously published cutoffs (25, 30, 36, 42).”
ResultTan, 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., et al. (2023) · Endocrine Connections · doi:10.1530/ec-23-0004 · Cited by 10 · see citing works
- Authors
- Dušková, M., Šimůnková, K., Vítků, J., Sosvorová, L., Jandíková, H., Pospíšilová, H., Šrámková, M., Kosák, M., Kršek, M., Hána, V., Žánová, M., Springer, D., & Stárka, L.
- Affiliations
- Institute of Endocrinology (CZ)
- Charles University (CZ)
- Corresponding author
- Dušková, Michaela
- Šimůnková, Kateřina
- Vítků, Jana
- Jandíková, Hana
- Pospíšilová, Hana
- Šrámková, Monika
- Kosák, Mikuláš
- Kršek, Michal
- Hána, Václav
- Žánová, Magdaléna
- Springer, Drahomíra
- Stárka, Luboslav
- ORCID
- Venue
- Prague Medical Report
- Published
- 2016
- Volume
- 117
- Issue
- 1
- Pages
- 18-33
- ISSN
- 0036-5327 (ISSN-L)
- 1214-6994
- 2336-2936
- OpenAlex
- W2309978719
- Cited by
- 11
- References
- 38
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 2
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Prague Medical Report (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministerstvo Zdravotnictví Ceské Republiky
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- adrenal insufficiency, hypothalamic-pituitary-adrenal axis, ACTH stimulation test, insulin tolerance test, salivary cortisol, salivary cortisone, pregnenolone, dehydroepiandrosterone, diagnostic accuracy, healthy men
- MeSH terms
- Adrenal Insufficiency, Adult, Chromatography, Liquid, Cosyntropin, Dehydroepiandrosterone, Diagnostic Tests, Routine, Hormones, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Pituitary-Adrenal System, Pregnenolone, Saliva, Healthy Volunteers
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