79
views
0
recommends
+1 Recommend
2 collections
    0
    shares

          The flagship journal of the Society for Endocrinology. Learn more

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Late-night salivary cortisol and cortisone should be the initial screening test for Cushing’s syndrome

      research-article

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Endogenous Cushing’s syndrome (CS) poses considerable diagnostic challenges. Although late-night salivary cortisol (LNSC) is recommended as a first-line screening investigation, it remains the least widely used test in many countries. The combined measurement of LNSC and late-night salivary cortisone (LNS cortisone) has shown to further improve diagnostic accuracy. We present a retrospective study in a tertiary referral centre comparing LNSC, LNS cortisone, overnight dexamethasone suppression test, low-dose dexamethasone suppression test and 24-h urinary free cortisol results of patients investigated for CS. Patients were categorised into those who had CS (21 patients) and those who did not (33 patients). LNSC had a sensitivity of 95% and a specificity of 91%. LNS cortisone had a specificity of 100% and a sensitivity of 86%. With an optimal cut-off for LNS cortisone of >14.5 nmol/L the sensitivity was 95.2%, and the specificity was 100% with an area under the curve of 0.997, for diagnosing CS. Saliva collection is non-invasive and can be carried out at home. We therefore advocate simultaneous measurement of LNSC and LNS cortisone as the first-line screening test to evaluate patients with suspected CS.

          Related collections

          Most cited references23

          • Record: found
          • Abstract: found
          • Article: not found

          The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline.

          The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushing's syndrome. The Task Force included a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage the Task Force incorporated needed changes in response to written comments. After excluding exogenous glucocorticoid use, we recommend testing for Cushing's syndrome in patients with multiple and progressive features compatible with the syndrome, particularly those with a high discriminatory value, and patients with adrenal incidentaloma. We recommend initial use of one test with high diagnostic accuracy (urine cortisol, late night salivary cortisol, 1 mg overnight or 2 mg 48-h dexamethasone suppression test). We recommend that patients with an abnormal result see an endocrinologist and undergo a second test, either one of the above or, in some cases, a serum midnight cortisol or dexamethasone-CRH test. Patients with concordant abnormal results should undergo testing for the cause of Cushing's syndrome. Patients with concordant normal results should not undergo further evaluation. We recommend additional testing in patients with discordant results, normal responses suspected of cyclic hypercortisolism, or initially normal responses who accumulate additional features over time.
            • Record: found
            • Abstract: found
            • Article: not found

            Measuring cortisol in serum, urine and saliva - are our assays good enough?

            Cortisol is a steroid hormone produced in response to stress. It is essential for maintaining health and wellbeing and leads to significant morbidity when deficient or present in excess. It is lipophilic and is transported bound to cortisol-binding globulin (CBG) and albumin; a small fraction (∼10%) of total serum cortisol is unbound and biologically active. Serum cortisol assays measure total cortisol and their results can be misleading in patients with altered serum protein concentrations. Automated immunoassays are used to measure cortisol but lack specificity and show significant inter-assay differences. Liquid chromatography - tandem mass spectrometry (LC-MS/MS) offers improved specificity and sensitivity; however, cortisol cut-offs used in the short Synacthen and Dexamethasone suppression tests are yet to be validated for these assays. Urine free cortisol is used to screen for Cushing's syndrome. Unbound cortisol is excreted unchanged in the urine and 24-h urine free cortisol correlates well with mean serum-free cortisol in conditions of cortisol excess. Urine free cortisol is measured predominantly by immunoassay or LC-MS/MS. Salivary cortisol also reflects changes in unbound serum cortisol and offers a reliable alternative to measuring free cortisol in serum. LC-MS/MS is the method of choice for measuring salivary cortisol; however, its use is limited by the lack of a single, validated reference range and poorly standardized assays. This review examines the methods available for measuring cortisol in serum, urine and saliva, explores cortisol in disease and considers the difficulties of measuring cortisol in acutely unwell patients and in neonates.
              • Record: found
              • Abstract: found
              • Article: not found

              Salivary cortisone is a potential biomarker for serum free cortisol.

              Salivary cortisol measurement is used as a practical surrogate for serum free cortisol. However, parotid tissue harbors 11β-hydroxysteroid dehydrogenase (11β-HSD2) activity converting cortisol to cortisone. This study was designed to assess the impact of parotid 11β-HSD2 activity on the measurement of salivary cortisol. PATIENTS, DESIGN, AND OUTCOME MEASURES: Study participants with changes in circulating corticosteroid-binding globulin (CBG) (±oral contraceptive, functionally CBG null) and controls were studied during adrenal stimulation by ACTH and postoral and iv hydrocortisone administration. Simultaneous serum and saliva samples were collected for the measurement of total serum cortisol (SerF) by immunoassay, and unbound cortisol and cortisone in serum (FreeF and FreeE) and saliva (SalF and SalE) by liquid chromatography-tandem mass spectrometry. ACTH stimulation increased SerF, FreeF, SalF, SalE, but not FreeE in all individuals. SerF significantly decreased after stopping oral contraceptive administration, but FreeF, SalF and SalE remained unchanged. In the hydrocortisone administration study, individual FreeF and SalE curves were nearly identical and SalE closely reflected FreeF in all participants, irrespective of CBG changes. The highest correlation in all (n = 537) matched serum-saliva samples was between SalE and FreeF (r = 0.95, P < 0.0001), and there was no evidence of 11β-HSD2 saturation. Salivary cortisol is a useful surrogate for circulating free cortisol, but its concentration is determined both by serum free cortisol and parotid metabolism to cortisone. We have shown that salivary cortisone closely reflects free serum cortisol after adrenal stimulation and hydrocortisone administration and is unaffected by CBG changes. Salivary cortisone has potential as a useful surrogate for serum free cortisol in research and clinical assessment, and further research in states of chronic glucocorticoid excess is now needed.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                07 June 2022
                01 July 2022
                : 11
                : 7
                : e220050
                Affiliations
                [1 ]Department of Endocrinology , Imperial College Healthcare NHS Trust, London, UK
                [2 ]Imperial College School of Medicine , Department of Biochemistry, Imperial College Healthcare NHS Trust, London, UK
                [3 ]Division of Diabetes , Endocrinology and Metabolism, Imperial College London, London, UK
                [4 ]Department of Biochemistry , Imperial College Healthcare NHS Trust, London, UK
                Author notes
                Correspondence should be addressed to F Wernig: f.wernig@ 123456imperial.ac.uk
                Author information
                http://orcid.org/0000-0003-4538-4071
                http://orcid.org/0000-0002-0309-129X
                http://orcid.org/0000-0003-1256-5407
                http://orcid.org/0000-0001-5914-9318
                Article
                EC-22-0050
                10.1530/EC-22-0050
                9254321
                35671282
                3ba2c22e-b343-4e47-be86-9d2422fd0c24
                © The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 18 May 2022
                : 07 June 2022
                Categories
                Research

                salivary cortisol,salivary cortisone,cushing’s syndrome,screening

                Comments

                Comment on this article

                Related Documents Log