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Salivary cortisol and cortisone in diagnosis of Cushing's syndrome - A comparison of six different analytical methods

Bäcklund, Nils ; Brattsand, Göran ; Lundstedt, Staffan ; Aardal, Elisabeth ; Bartuseviciene, Inga ; Berinder, Katarina ; Höybye, Charlotte ; Burman, Pia LU ; Edén Engström, Britt and Isaksson, Anders LU , et al. (2023) In Clinical Chemistry and Laboratory Medicine 61(10). p.1780-1791
Abstract

Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushing's syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS. Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate... (More)

Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushing's syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS. Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves. URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4-3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7-1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5-16.6 nmol/L at 23:00 h and 3.0-3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs ≥0.96. We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cushing's syndrome, immunoassay, LC-MS/MS, method comparison, salivary cortisol, salivary cortisone
in
Clinical Chemistry and Laboratory Medicine
volume
61
issue
10
pages
1780 - 1791
publisher
De Gruyter
external identifiers
  • pmid:37013440
  • scopus:85151863068
ISSN
1434-6621
DOI
10.1515/cclm-2023-0141
language
English
LU publication?
yes
id
92fa7eff-2b03-432a-be86-c6719077684d
date added to LUP
2023-07-20 12:40:59
date last changed
2024-04-20 00:52:33
@article{92fa7eff-2b03-432a-be86-c6719077684d,
  abstract     = {{<p>Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushing's syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS. Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves. URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4-3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7-1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5-16.6 nmol/L at 23:00 h and 3.0-3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs ≥0.96. We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.</p>}},
  author       = {{Bäcklund, Nils and Brattsand, Göran and Lundstedt, Staffan and Aardal, Elisabeth and Bartuseviciene, Inga and Berinder, Katarina and Höybye, Charlotte and Burman, Pia and Edén Engström, Britt and Isaksson, Anders and Blomgren, Anders and Ragnarsson, Oskar and Rüetschi, Ulrika and Wahlberg, Jeanette and Olsson, Tommy and Dahlqvist, Per}},
  issn         = {{1434-6621}},
  keywords     = {{Cushing's syndrome; immunoassay; LC-MS/MS; method comparison; salivary cortisol; salivary cortisone}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{1780--1791}},
  publisher    = {{De Gruyter}},
  series       = {{Clinical Chemistry and Laboratory Medicine}},
  title        = {{Salivary cortisol and cortisone in diagnosis of Cushing's syndrome - A comparison of six different analytical methods}},
  url          = {{http://dx.doi.org/10.1515/cclm-2023-0141}},
  doi          = {{10.1515/cclm-2023-0141}},
  volume       = {{61}},
  year         = {{2023}},
}