Use of salivary cortisol and cortisone in the high- and low-dose synacthen test
Abstract
CONTEXT: Salivary cortisone reflects serum cortisol levels, is more sensitive than salivary cortisol at lower values of serum cortisol and is noninvasive. OBJECTIVE: To investigate the relationship between serum cortisol and salivary cortisol and cortisone following low- and high-dose synacthen. DESIGN AND SETTING: Prospective pharmacodynamic studies in clinical research facilities. PARTICIPANTS AND INTERVENTION: Thirty-five dexamethasone-suppressed, healthy adult males underwent an intravenous synacthen test: N = 23 low-dose (1 mcg), N = 12 high-dose (250 mcg). Paired serum and salivary samples were taken at 15 sampling points over 120 minutes. MAIN OUTCOME MEASURE: Serum cortisol and salivary cortisol and cortisone were analysed for correlations and by a mixed-effects model. RESULTS: At baseline, the correlation between serum cortisol and salivary cortisol was weak with many samples undetectable (r = .45, NS), but there was a strong correlation with salivary cortisone (r = .94, P < .001). Up to 50 minutes following synacthen, the correlation coefficient between serum cortisol and salivary cortisol and cortisone was <0.8, but both had a stronger correlation at 60 minutes (salivary cortisol r = .89, P < .001, salivary cortisone r = .85, P < .001). The relationship was examined excluding samples in the dynamic phase (baseline to 60 minutes). Salivary cortisol and cortisone showed a close relationship to serum cortisol. Salivary cortisone showed the stronger correlation: salivary cortisol r = .82, P < .001, salivary cortisone r = .96, P < .001. CONCLUSION: Following synacthen, both salivary cortisol and cortisone reflect serum cortisol levels, but there is a lag in their rise up to 60 minutes. The results support further research for possible future use of a 60-minute salivary cortisone measurement during the synacthen test.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline.
Nieman, L. K., Biller, B. M. K., Findling, J. W., Newell-Price, J., Savage, M. O., Stewart, P. M., & Montori, V. M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0125 · Cited by 2,718 · see citing works
Bornstein, S. R., Allolio, B., Arlt, W., Barthel, A., Don-Wauchope, A., Hammer, G. D., Husebye, E. S., Merke, D. P., Murad, M. H., Stratakis, C. A., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1710 · Cited by 1,769 · see citing works
Charmandari, E., Nicolaides, N. C., & Chrousos, G. P. (2014) · The Lancet · doi:10.1016/s0140-6736(13)61684-0 · Cited by 644 · see citing works
DICKSTEIN, G., SHECHNER, C., NICHOLSON, W. E., ROSNER, I., SHEN-ORR, Z., ADAWI, F., & LAHAV, M. (1991) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-72-4-773 · Cited by 457 · see citing works
Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis
Kazlauskaite, R., Evans, A. T., Villabona, C. V., Abdu, T. A. M., Ambrosi, B., Atkinson, A. B., Choi, C. H., Clayton, R. N., Courtney, C. H., Gonc, E. N., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0710 · Cited by 385 · see citing works
Diagnosis of Adrenal Insufficiency
Dorin, R. I., Qualls, C. R., & Crapo, L. M. (2003) · Annals of Internal Medicine · doi:10.7326/0003-4819-139-3-200308050-00009 · Cited by 374 · see citing works
Ospina, N. S., Al Nofal, A., Bancos, I., Javed, A., Benkhadra, K., Kapoor, E., Lteif, A. N., Natt, N., & Murad, M. H. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1700 · Cited by 247 · see citing works
Salivary cortisone is a potential biomarker for serum free cortisol
Perogamvros, I., Keevil, B. G., Ray, D. W., & Trainer, P. J. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1215 · Cited by 222 · see citing works
Self-citationPerogamvros, I., Owen, L. J., Newell-Price, J., Ray, D. W., Trainer, P. J., & Keevil, B. G. (2009) · Journal of Chromatography B · doi:10.1016/j.jchromb.2009.09.014 · Cited by 140 · see citing works
Self-citationDebono, M., Harrison, R. F., Whitaker, M. J., Eckland, D., Arlt, W., Keevil, B. G., & Ross, R. J. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3694 · Cited by 128 · see citing works
Self-citationArafah, B., Nishiyama, F. J., Tlaygeh, H., & Hejal, R. (2007) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2007-0181 · Cited by 121 · see citing works
Responses of plasma adrenocortical steroids to low dose ACTH in normal subjects
Daidoh, H., Morita, H., Mune, T., Murayama, M. A., Hanafusa, J., Ni, H., Shibata, H., & Yasuda, K. (1995) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1995.tb02037.x · Cited by 120 · see citing works
Jung, C., Greco, S., Nguyen, H. H., Ho, J. T., Lewis, J. G., Torpy, D. J., & Inder, W. J. (2014) · BMC Endocrine Disorders · doi:10.1186/1472-6823-14-91 · Cited by 114 · see citing works
Nye, E. J., Grice, J., Hockings, G. I., Strakosch, C., Crosbie, G., Walters, M., & Jackson, R. V. (1999) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jcem.84.10.6062 · Cited by 88 · see citing works
Low-dose ACTH (1 µg) salivary test: a potential alternative to the classical blood test
Marcus‐Perlman, Y., Tordjman, K., Greenman, Y., Limor, R., Shenkerman, G., Osher, E., & Stern, N. (2006) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2006.02451.x · Cited by 62 · see citing works
Magnotti, M., & Shimshi, M. (2008) · Endocrine Practice · doi:10.4158/ep.14.2.233 · Cited by 62 · see citing works
Nye, E. J. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.10.3648 · Cited by 62 · see citing works
Perogamvros, I., Owen, L. J., Keevil, B. G., Brabant, G., & Trainer, P. J. (2010) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03582.x · Cited by 61 · see citing works
Contreras, L. N., Arregger, A. L., Persi, G. G., González, N., & Cardoso, E. M. L. (2004) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2004.02144.x · Cited by 60 · see citing works
Deutschbein, T., Unger, N., Mann, K., & Petersenn, S. (2009) · European Journal of Endocrinology · doi:10.1530/eje-08-0600 · Cited by 52 · see citing works
Blair, J., Lancaster, G., Titman, A., Peak, M., Newlands, P., Collingwood, C., Chesters, C., Moorcroft, T., Wallin, N., Hawcutt, D. B., et al. (2013) · Clinical Endocrinology · doi:10.1111/cen.12302 · Cited by 38 · see citing works
Ng, S. M., Agwu, J. C., & Dwan, K. M. (2016) · Archives of Disease in Childhood · doi:10.1136/archdischild-2015-308925 · Cited by 36 · see citing works
Salivary cortisol and cortisone responses to tetracosactrin (synacthen)
Cornes, M. P., Ashby, H. L., Khalid, Y., Buch, H. N., Ford, C., & Gama, R. (2015) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/0004563215577838 · Cited by 27 · see citing works
Mak, I. Y. F., Au Yeung, B. Y. T., Ng, Y. W., Choi, C. H., Iu, H. Y. P., Shek, C. C., & Tiu, S. C. (2017) · Journal of the Endocrine Society · doi:10.1210/js.2016-1056 · Cited by 20 · see citing works
The short Synacthen test: a questionnaire survey of current usage
Elder, C. J., Sachdev, P., & Wright, N. P. (2012) · Archives of Disease in Childhood · doi:10.1136/archdischild-2012-301713 · Cited by 19 · see citing works
Measurement of salivary cortisone to assess the adequacy of hydrocortisone replacement
Raff, H. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1228 · Cited by 19 · see citing works
Salivary cortisol or cortisone?
Raff, H., & Findling, J. W. (2010) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.192 · Cited by 14 · see citing works
Brixey-McCann, R., Tennant, S., Geen, J., Armston, A., Barth, J. H., Keevil, B., Rees, A., & Evans, C. (2015) · Endocrine Abstracts · doi:10.1530/endoabs.38.p22 · Cited by 8 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [17]17. Kazlauskaite R, Evans AT, Villabona CV, et al. Corticotropin Tests for Hypothalamic-PituitaryAdrenal Insufficiency: A Metaanalysis. Journal of Clinical Endocrinology & Metabolism. 2008;93(11):4245-4253.
Cited by
Sorted by citations
Reduced sound-evoked and resting-state BOLD fMRI connectivity in tinnitus
Hofmeier, B., Wolpert, S., Aldamer, E. S., Walter, M., Thiericke, J. P., Braun, C., Zelle, D., Rüttiger, L., Klose, U., & Knipper, M. (2018) · NeuroImage Clinical · doi:10.1016/j.nicl.2018.08.029 · Cited by 82 · see citing works
Primary adrenal insufficiency in children: Diagnosis and management
Kırkgöz, T., & Güran, T. (2018) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2018.05.010 · Cited by 80 · see citing works
Raff, H., & Phillips, J. M. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00186 · Cited by 53 · see citing works
Bacila, I. A., Adaway, J., Hawley, J. M., Mahdi, S., Krone, R. E., Patel, L., Alvi, S., Randell, T. L., Gevers, E. F., Dattani, M., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00031 · Cited by 44 · see citing works
Botia, M., Escribano, D., Martı́nez-Subiela, S., Tvarijonaviciute, A., Tecles, F., López-Arjona, M., & Cerón, J. M. C. (2023) · Metabolites · doi:10.3390/metabo13010106 · Cited by 37 · see citing works
Stimulated Salivary Cortisol as a Noninvasive Diagnostic Tool for Adrenal Insufficiency
Kim, Y. J., Kim, J. H., Hong, A. R., Park, K. S., Kim, S. W., Shin, C. S., & Kim, S. Y. (2020) · Endocrinology and Metabolism · doi:10.3803/enm.2020.707 · Cited by 30 · see citing works
Burgos, N., Ghayee, H. K., & Ospina, N. S. (2019) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000473 · Cited by 27 · see citing works
Garnacho‐Castaño, M. V., Palau-Salvà, G., Serra‐Payá, N., Ruiz-Hermosel, M., Berbell, M., Viñals, X., Bataller, M. G., Carbonell, T., Vilches-Saez, S., Pleguezuelos, E., et al. (2020) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-020-00388-z · Cited by 22 · see citing works
Elder, C. J., Vilela, R., Johnson, T. N., Taylor, R. N., Kemp, E. H., Keevil, B. G., Cross, A. S., Ross, R. J. M., & Wright, N. P. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa323 · Cited by 16 · see citing works
Resztak, M., Czyrski, A., & Sobiak, J. (2025) · Pharmacological Reports · doi:10.1007/s43440-025-00732-7 · Cited by 16 · see citing works
Vaiani, E., Lazzati, J. M., Ramírez, P., Costanzo, M., Gil, S., Dratler, G., Zaidman, V., Chaler, E., & Belgorosky, A. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00304 · Cited by 14 · see citing works
El‐Farhan, N., Tennant, S., Rees, S. E., Evans, C., & Rees, A. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad576 · Cited by 14 · see citing works
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
“Interestingly, recent data also show good diagnostic properties for salivary cortisone sampling on awakening as a screening test for AI (45, 46).”
BackgroundTan, 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
Investigating cortisol excess or deficiency: a practical approach
Hanna, F., Issa, B. G., Kevil, B., & Fryer, A. A. (2019) · BMJ · doi:10.1136/bmj.l6039 · Cited by 9 · see citing works
Ciancia, S., van den Berg, S. A. A., & van den Akker, E. L. T. (2023) · Children · doi:10.3390/children10091569 · Cited by 8 · see citing works
Kalaria, T., Agarwal, M., Kaur, S., Hughes, L., Sharrod-Cole, H., Chaudhari, R., Gherman-Ciolac, C., Chopra, R., Okeke, V., Ford, C., et al. (2020) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/0004563220961745 · Cited by 7 · see citing works
Dennedy, M. C. (2018) · Clinical Endocrinology · doi:10.1111/cen.13585 · Cited by 3 · see citing works
Hypothalamic–pituitary–adrenal suppression
Kelsall, A., & Newell-Price, J. D. C. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00139-4
Date, K. L., Baster, K., Caunt, S., Cohen, J., Debono, M., Fearnside, J., Johnson, T. N., Ross, R. J. M., Taylor, R. N., & Elder, C. J. (2024) · BMJ Open · doi:10.1136/bmjopen-2024-094830
AbdulWahab, A., Alsiddig, R., Al-Naimi, A. R., Maarafiya, M., Abushahin, A., Hani, Y., Singh, R., Jerobin, J., Bettahi, I., & Abu‐Hasan, M. (2026) · Journal of Asthma and Allergy · doi:10.2147/jaa.s600420
- Authors
- Elder, C. J., Harrison, R. F., Cross, A. S., Vilela, R., Keevil, B. G., Wright, N. P., & Ross, R. J.
- Affiliations
- University of Sheffield (GB)
- Department of Clinical Biochemistry University Hospital of South Manchester NHS Trust Manchester UK
- Sheffield Children's NHS Foundation Trust (GB)
- Corresponding author
- Ross, Richard J.
- ORCID
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2017-11-29
- Volume
- 88
- Issue
- 6
- Pages
- 772-778
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2767762237
- Cited by
- 21
- References
- 28
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 4 · 2020: 4 · 2019: 5 · 2018: 3
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Funders
- Medical Research Council
- Glasgow Children's Hospital Charity
- 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
- salivary cortisol, salivary cortisone, serum cortisol, ACTH stimulation test, dexamethasone suppression
- MeSH terms
- Adult, Cortisone, Cosyntropin, Humans, Hydrocortisone, Male, Middle Aged, Prospective Studies, Saliva, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review