Reference ranges of late-night salivary cortisol and cortisone measured by LC-MS/MS and accuracy for the diagnosis of cushing's syndrome
Abstract
Purpose International guidelines recommend salivary cortisol for the diagnosis of Cushing's syndrome. Despite mass spectrometry-based assays are considered the analytical gold-standard, there is still the need to define reference intervals and diagnostic accuracy of such methodology.Methods 100 healthy volunteers and 50 consecutive patients were enrolled to compare LC-MS/MS and electrochemiluminescence assay for the determination of late-night salivary cortisol and cortisone. Moreover, we aimed to determine reference intervals of salivary steroids in a population of healthy individuals and diagnostic accuracy in patients with suspected hypercortisolism and in a population including also healthy individuals.Results Method comparison highlighted a positive bias (51.8%) of immunoassay over LC-MS/MS. Reference intervals of salivary cortisol (0.17-0.97 µg/L), cortisone (0.84-4.85 µg/L) and ratio (0.08-0.30) were obtained. The most accurate thresholds of salivary cortisol for the diagnosis of hypercortisolism were 1.15 µg/L in the population with suspected hypercortisolism (AUC 1) and 1.30 µg/L in the population including also healthy individuals (AUC 1). Cut-off values of salivary cortisone (7.23 µg/L; Se 92.9%, Sp 97.2%, AUC 0.960 and Se 92.9%, Sp 99.1%, AUC 0.985 in suspected hypercortisolism and in overall population, respectively) and cortisol-to-cortisone ratio (0.20; Se 85.7%, Sp 80.6%, AUC 0.820 and Se 85.7%, Sp 85.5%, AUC 0.855 in suspected hypercortisolism and in overall population, respectively) were accurate and similar in both populations.Conclusion LC-MS/MS is the most accurate analytical platform for measuring salivary steroids. Obtained reference intervals are coherent with previously published data and diagnostic accuracy for diagnosis of overt hypercortisolism proved highly satisfactory.
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LNSC is well-established as a first-line screening test for patients with CS.
“LNSC is well-established as a first-line screening test for patients with CS (7–10).”
From The diagnostic value of salivary cortisol and salivary cortisone in patients with suspected hypercortisolism (2022) · cites this paper as [10]
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- Authors
- Ponzetto, F., Settanni, F., Parasiliti-Caprino, M., Rumbolo, F., Nonnato, A., Ricciardo, M., Amante, E., Priolo, G., Vitali, S., Anfossi, L., Arvat, E., Ghigo, E., Giordano, R., & Mengozzi, G.
- Affiliations
- University of Turin (IT)
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- ORCID
- Venue
- Journal of Endocrinological Investigation
- Published
- 2020-08-09
- Volume
- 43
- Issue
- 12
- Pages
- 1797-1806
- ISSN
- 0391-4097 (ISSN-L)
- 1720-8386
- OpenAlex
- W3048270531
- Cited by
- 25
- References
- 45
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 1
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Endocrinological Investigation (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Keywords
- Cushing's syndrome, salivary cortisol, salivary cortisone, reference values, LC-MS/MS assay, electrochemiluminescence immunoassay, method comparison, diagnostic accuracy
- MeSH terms
- Adolescent, Adult, Chromatography, Liquid, Circadian Rhythm, Cortisone, Cushing Syndrome, Female, Humans, Hydrocortisone, Male, Middle Aged, Pituitary-Adrenal Function Tests, Predictive Value of Tests, Reference Values, Saliva, Reproducibility of Results, Case-Control Studies, Tandem Mass Spectrometry, Young Adult, Healthy Volunteers
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