Hypothalamic-pituitary-adrenal axis suppression: the value of salivary cortisol and cortisone in assessing hypothalamic-pituitary-adrenal recovery
Abstract
BACKGROUND: The 0.25 mg short synacthen test is used to assess recovery from hypothalamic-pituitary-adrenal suppression due to chronic glucocorticoid administration. We assessed the potential role of salivary cortisol and cortisone in predicting hypothalamic-pituitary-adrenal function using the short synacthen test as the gold standard test. METHOD: Between 09:00 and 10:30, salivary and blood samples were collected just prior to a short synacthen test to assess hypothalamic-pituitary-adrenal axis recovery in patients previously treated with oral glucocorticoids. The cut-off for a normal short synacthen test was a 30-min cortisol ≥450 nmol/L. RESULTS: Fifty-six short synacthen tests were performed on 47 patients. Of these, 15 were normal. The area under receiver operating characteristic curves for serum cortisol, salivary cortisone and salivary cortisol were 0.772, 0.785 and 0.770, respectively. From the receiver operating characteristic analysis, the cut-offs for baseline serum cortisol (≥365 nmol/L) and salivary cortisone (≥37.2 nmol) predicted hypothalamic-pituitary-adrenal axis recovery with 100% specificity in 26.7% of pass short synacthen tests, whereas salivary cortisol predicted none. Baseline serum cortisol (≤170 nmol/L), salivary cortisone (≤9.42 nmol/L) and salivary cortisol (≤1.92 nmol/L) predicted hypothalamic-pituitary-adrenal suppression with 100% sensitivity in 58.5%, 53.7% and 51.2% of failed short synacthen tests, respectively. Using these cut-offs, baseline serum cortisol, salivary cortisone and salivary cortisol could reduce the need for short synacthen tests by 50%, 46% and 37%, respectively. CONCLUSION: Although marginally inferior to early morning serum cortisol, early morning salivary cortisone may be used as a first-line test for assessing hypothalamic-pituitary-adrenal function. We plan to incorporate salivary cortisone into a home-based patient pathway to identify patients with hypothalamic-pituitary-adrenal recovery, continuing hypothalamic-pituitary-adrenal suppression and those who require a short synacthen test.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [42]
Cites
Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol
Van Cauter, E. (1996) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.81.7.2468 · Cited by 951 · 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
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
El‐Farhan, N., Pickett, A., Ducroq, D., Bailey, C., Mitchem, K., Morgan, N., Armston, A., Jones, L., Evans, C., & Rees, D. A. (2013) · Clinical Endocrinology · doi:10.1111/cen.12039 · Cited by 158 · see citing works
Woods, C. P., Argese, N., Chapman, M., Boot, C., Webster, R., Dabhi, V., Grossman, A. B., Toogood, A. A., Arlt, W., Stewart, P. M., et al. (2015) · European Journal of Endocrinology · doi:10.1530/eje-15-0608 · Cited by 152 · see citing works
Perogamvros, 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
Klose, M., Lange, M., Rasmussen, A. K., Skakkebæk, N. E., Hilsted, L., Haug, E., Andersen, M., & Feldt-Rasmussen, U. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1791 · Cited by 140 · see citing works
Qureshi, A. C., Bahri, A., Breen, L. A., Barnes, S. C., Powrie, J. K., Thomas, S. M., & Carroll, P. V. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.02784.x · Cited by 133 · see citing works
Debono, 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
Impact of age, sex and body mass index on cortisol secretion in 143 healthy adults
Roelfsema, F., van Heemst, D., Iranmanesh, A., Takahashi, P., Yang, R., & Veldhuis, J. D. (2017) · Endocrine Connections · doi:10.1530/ec-17-0160 · Cited by 100 · see citing works
Is a 0900-h serum cortisol useful prior to a short Synacthen test in outpatient assessment?
le Roux, C., Meeran, K., & Alaghband-Zadeh, J. (2002) · Annals of Clinical Biochemistry: International Journal of Laboratory Medicine · doi:10.1258/0004563021901919 · Cited by 77 · see citing works
Pofi, R., Feliciano, C., Sbardella, E., Argese, N., Woods, C. P., Grossman, A. B., Jafar-Mohammadi, B., Gleeson, H., Lenzi, A., Isidori, A. M., et al. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-00529 · Cited by 67 · 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
Maguire, A., Biesheuvel, C. J., Ambler, G. R., Moore, B., McLean, M. P., & Cowell, C. T. C. T. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.03100.x · Cited by 46 · see citing works
The effect of serum matrix and gender on cortisol measurement by commonly used immunoassays
Dodd, A., Ducroq, D., Neale, S., Wise, M., Mitchem, K., Armston, A., Barth, J., El-Farhan, N., Rees, D., & Evans, C. (2014) · Annals of Clinical Biochemistry: International Journal of Laboratory Medicine · doi:10.1177/0004563213514567 · Cited by 34 · 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
Self-citationUse of salivary cortisol and cortisone in the high- and low-dose synacthen test
Elder, C. J., Harrison, R. F., Cross, A. S., Vilela, R., Keevil, B. G., Wright, N. P., & Ross, R. J. (2018) · Clinical Endocrinology · doi:10.1111/cen.13509 · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kalaria, T., Buch, H., Agarwal, M., Chaudhari, R., Gherman‐Ciolac, C., Chopra, R., Okeke, V., Kaur, S., Hughes, L., Sharrod‐Cole, H., et al. (2022) · Clinical Endocrinology · doi:10.1111/cen.14388 · Cited by 14 · see citing works
Self-citationBitencourt, M. R., Batista, R. L., Biscotto, I. P., & Carvalho, L. R. S. (2022) · Archives of Endocrinology and Metabolism · doi:10.20945/2359-3997000000493 · 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
“The validity of our calculated LRLs for salivary cortisol and cortisone is strengthened by the similarities to previously published cutoffs (25, 30, 36, 42).”
ResultZhai, P., Liu, H., Zhang, Y., Huang, T., Xiong, C., Liu, Y., Wang, G., Chen, X., Tan, J., Jiao, C., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1193266 · Cited by 3 · see citing works
Perioperative Management of Endocrine Problems in Pediatric Cardiac Surgery Patients
Hashemipour, M., Dehkordi, E. H., Mostofizadeh, N., Soheilipour, F., Ghasemi, M., Mazaheri, A., & Rostampour, N. (2023) · Springer eBooks · doi:10.1007/978-3-031-10442-8_45
Honour, J. W. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-818124-9.00011-5
- Authors
- Kalaria, T., Agarwal, M., Kaur, S., Hughes, L., Sharrod-Cole, H., Chaudhari, R., Gherman-Ciolac, C., Chopra, R., Okeke, V., Ford, C., Buch, H., & Gama, R.
- Affiliations
- The Royal Wolverhampton NHS Trust (GB)
- Blood Sciences, Royal Wolverhampton NHS Trust, Wolverhampton, UK
- Endocrinology and Diabetes, Royal Wolverhampton NHS Trust, Wolverhampton, UK
- University of Wolverhampton (GB)
- Corresponding author
- Kalaria, Tejas
- Venue
- Annals of Clinical Biochemistry International Journal of Laboratory Medicine
- Publisher
- SAGE Publications
- Published
- 2020-10-13
- Volume
- 57
- Issue
- 6
- Pages
- 456-460
- ISSN
- 0004-5632 (ISSN-L)
- 1758-1001
- OpenAlex
- W3087829160
- Cited by
- 7
- References
- 17
- Citations by year
- 2024: 2 · 2023: 3 · 2022: 1 · 2020: 1
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Clinical Biochemistry International Journal of Laboratory Medicine (publishedVersion)
- PubMed (publishedVersion)
- 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 › Pituitary Gland Disorders and Treatments
- Keywords
- salivary cortisone, salivary cortisol, ACTH stimulation test, chronic glucocorticoid therapy, serum cortisol, home-based assessment, diagnostic thresholds
- MeSH terms
- Administration, Oral, Aged, Cortisone, Female, Glucocorticoids, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Middle Aged, Pituitary-Adrenal System, Saliva
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
