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Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing's syndrome

Bäcklund, Nils ; Brattsand, Göran ; Israelsson, Marlen ; Ragnarsson, Oskar ; Burman, Pia LU ; Edén Engström, Britt ; Høybye, Charlotte ; Berinder, Katarina ; Wahlberg, Jeanette and Olsson, Tommy , et al. (2020) In European Journal of Endocrinology 182(6). p.569-582
Abstract

Objective: The challenge of diagnosing Cushing's syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST). Design and methods: Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th... (More)

Objective: The challenge of diagnosing Cushing's syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST). Design and methods: Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves. Results: The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70-99%) and specificity of 96% (91-98%) for cortisol, and a 100% (84-100%) sensitivity and 95% (90-98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75-100%) sensitivity and 96% (92-99%) specificity with cortisol, and 100% (83-100%) sensitivity and 94% (89-97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h. Conclusion: Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better.

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Contribution to journal
publication status
published
subject
in
European Journal of Endocrinology
volume
182
issue
6
pages
14 pages
publisher
Society of the European Journal of Endocrinology
external identifiers
  • pmid:32213657
  • scopus:85084187749
ISSN
1479-683X
DOI
10.1530/EJE-19-0872
language
English
LU publication?
yes
id
bbee6383-6f24-4ded-b244-64435614964d
date added to LUP
2020-06-02 15:33:19
date last changed
2020-09-23 08:11:22
@article{bbee6383-6f24-4ded-b244-64435614964d,
  abstract     = {<p>Objective: The challenge of diagnosing Cushing's syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST). Design and methods: Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves. Results: The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70-99%) and specificity of 96% (91-98%) for cortisol, and a 100% (84-100%) sensitivity and 95% (90-98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75-100%) sensitivity and 96% (92-99%) specificity with cortisol, and 100% (83-100%) sensitivity and 94% (89-97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h. Conclusion: Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better.</p>},
  author       = {Bäcklund, Nils and Brattsand, Göran and Israelsson, Marlen and Ragnarsson, Oskar and Burman, Pia and Edén Engström, Britt and Høybye, Charlotte and Berinder, Katarina and Wahlberg, Jeanette and Olsson, Tommy and Dahlqvist, Per},
  issn         = {1479-683X},
  language     = {eng},
  number       = {6},
  pages        = {569--582},
  publisher    = {Society of the European Journal of Endocrinology},
  series       = {European Journal of Endocrinology},
  title        = {Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing's syndrome},
  url          = {http://dx.doi.org/10.1530/EJE-19-0872},
  doi          = {10.1530/EJE-19-0872},
  volume       = {182},
  year         = {2020},
}