Diagnostic performance of a newly developed salivary cortisol and cortisone measurement using an LC–MS/MS method with simple and rapid sample preparation
Abstract
Background Late-night salivary cortisol level is one of the first-line tests recommended by the Endocrine Society for the diagnosis of endogenous hypercortisolism. Most routine laboratories measure cortisol levels using immunoassay tests which fail to determine low cortisol levels accurately due to the numerous interfering substances. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with simple and rapid sample preparation was developed for the simultaneous measurement of cortisol and cortisone and its performance in the diagnosis of endogenous hypercortisolism was evaluated.Methods 324 late-night saliva samples were analyzed from which 272 samples were derived from patients with a suspected diagnosis of endogenous hypercortisolism. Salivary cortisol levels were assayed using an electrochemiluminescent immunoassay (ECLIA, Cortisol II, Roche), and simultaneous measurement of cortisol and cortisone was performed using an LC-MS/MS method.Results A strong correlation between cortisol results measured using ECLIA and LC-MS/MS (r 2 = 0.892) was demonstrated. Receiver operating characteristics (ROC) analysis showed good diagnostic performance of cortisol and cortisone levels assayed using LC-MS/MS method and for cortisol measured using ECLIA.Conclusions Late-night salivary cortisol and cortisone are useful parameters for the diagnosis of hypercortisolism. Using samples obtained from patients where the diagnosis of hypercortisolism is extremely challenging cut-off values for midnight salivary cortisol and cortisone measured by LC-MS/MS method were established.
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Diagnostic accuracy has not been shown to differ clearly between immunoassays and LC-MS/MS methods.
“However, no clear difference in diagnostic accuracy between IA and LC-MS/MS methods has been demonstrated [48].”
From Salivary cortisol and cortisone in diagnosis of Cushing's syndrome: a comparison of six different analytical methods (2023) · cites this paper as [48]
In most studies, LNSC was analyzed with immunochemical methods, which have lower analytical specificity than LC-MS/MS due to a risk of cross-reactions between cortisol and other steroid metabolites.
“In most of these studies LNSC was analyzed with immunochemical methods, i.e. methods with lower analytical specificity than LC-MS/MS due to a risk of cross-reactions between cortisol and other steroid metabolites (19, 20).”
From The diagnostic value of salivary cortisol and salivary cortisone in patients with suspected hypercortisolism (2022) · cites this paper as [19]
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- Authors
- Mészáros, K., Karvaly, G., Márta, Z., Magda, B., Tőke, J., Szücs, N., Tóth, M., Rácz, K., & Patócs, A.
- Affiliations
- Semmelweis University (HU)
- Corresponding author
- Patócs, A.
- Venue
- Journal of Endocrinological Investigation
- Published
- 2017-08-16
- Volume
- 41
- Issue
- 3
- Pages
- 315-323
- ISSN
- 0391-4097 (ISSN-L)
- 1720-8386
- OpenAlex
- W2747997849
- Cited by
- 27
- References
- 30
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 4
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Endocrinological Investigation (publishedVersion)
- PubMed (publishedVersion)
- Semmelweis University Repository (Semmelweis University) (submittedVersion)
- Funders
- Bionics Innovation Center (Grant for Medicinal Bionics)
- Magyar Tudományos Akadémia (Lendulet 2013)
- 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, endogenous hypercortisolism, electrochemiluminescence immunoassay, diagnostic thresholds, sample preparation
- MeSH terms
- Biological Assay, Chromatography, Liquid, Cortisone, Cushing Syndrome, Humans, Hydrocortisone, Prognosis, ROC Curve, Saliva, Biomarkers, Case-Control Studies, Tandem Mass Spectrometry
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