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Publications (10 of 12) Show all publications
Bäcklund, N., Lundstedt, S., Tornevi, A., Wihlbäck, A.-C., Olsson, T., Dahlqvist, P. & Brattsand, G. (2024). Salivary cortisol and cortisone can circumvent confounding effects of oral contraceptives in the short synacthen test. Journal of Clinical Endocrinology and Metabolism
Open this publication in new window or tab >>Salivary cortisol and cortisone can circumvent confounding effects of oral contraceptives in the short synacthen test
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2024 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197Article in journal (Refereed) Epub ahead of print
Abstract [en]

Context: Adrenal insufficiency (AI) is usually diagnosed by low plasma cortisol levels following a short Synacthen test (SST). Most plasma cortisol is bound to corticosteroid-binding globulin, which is increased by estrogen in combined estrogen-progestin oral contraceptives (COCs). Women with AI using COCs are therefore at risk of having an apparently normal plasma cortisol level during SST, which would not adequately reflect AI.

Objective: To test whether salivary cortisol or cortisone during SST is more robust against the COC effect and to calculate the lower reference limits (LRLs) for these to be used as tentative diagnostic cutoffs to exclude AI.

Methods: Forty-one healthy women on COCs and 46 healthy women without exogenous estrogens performed an SST with collection of plasma and salivary samples at 0, 30, and 60 min after Synacthen injection. The groups were compared using regression analysis with age as covariate and the LRLs were calculated parametrically.

Results: SST-stimulated plasma cortisol levels were significantly higher in the COC group versus controls, while mean salivary cortisol and cortisone levels were slightly lower in the COC group. Importantly, COC use did not significantly alter LRLs for salivary cortisol or cortisone. The smallest LRL difference between groups was seen for salivary cortisone.

Conclusion: Salivary cortisol and especially salivary cortisone are considerably less affected by COC use than plasma cortisol during SST. Due to similar LRLs, a common cutoff for salivary cortisol and cortisone during SST can be used to exclude AI in premenopausal women irrespective of COC use.

Place, publisher, year, edition, pages
Oxford University Press, 2024
Keywords
short Synacthen test, salivary cortisol, salivary cortisone, oral contraceptives, adrenal insufficiency, reference limits
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-222629 (URN)10.1210/clinem/dgad763 (DOI)001140071500001 ()38173358 (PubMedID)
Funder
Region VästerbottenUmeå University
Available from: 2024-03-22 Created: 2024-03-22 Last updated: 2024-03-25
Imamovic, M., Bäcklund, N., Lundstedt, S., Brattsand, G., Aardal, E., Olsson, T. & Dahlqvist, P. (2023). Confounding effects of liquorice, hydrocortisone, and blood contamination on salivary cortisol but not cortisone. Endocrine Connections, 12(1), Article ID e220324.
Open this publication in new window or tab >>Confounding effects of liquorice, hydrocortisone, and blood contamination on salivary cortisol but not cortisone
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2023 (English)In: Endocrine Connections, E-ISSN 2049-3614, Vol. 12, no 1, article id e220324Article in journal (Refereed) Published
Abstract [en]

Objective: To determine the effects of liquorice consumption, topical hydrocortisone, and blood contamination on salivary cortisol and cortisone concentrations.

Design and methods: Thirty healthy volunteers were randomized to a low, medium, or high dose of liquorice. Late-night saliva samples were collected using a Salivette® collection device at baseline, during 1 week of daily liquorice consumption, and during 4 weeks' washout. Saliva sampling was also performed before and after the application of topical hydrocortisone on the skin. Furthermore, in a subgroup (n  = 16), saliva and venous blood were collected from each individual and mixed to achieve graded blood contamination in saliva. Salivary cortisol and cortisone were analyzed with liquid chromatography-tandem mass spectrometry.

Results: Significant increases in salivary cortisol concentrations were observed during medium- (+49%) and high-dose (+97%) liquorice intake, which returned to baseline 4 days after liquorice withdrawal. Topical hydrocortisone on fingers holding the collection swab increased salivary cortisol concentrations >1000-fold with concomitant pronounced elevation of the cortisol:cortisone ratio. Salivary cortisol increased significantly after contamination with blood ≥0.5%. Visual examination could safely detect these samples. Salivary cortisone concentrations were unaffected by liquorice consumption and blood contamination, and only marginally affected by topical hydrocortisone.

Conclusion: Liquorice, topical hydrocortisone, and blood contamination may all cause elevated salivary cortisol concentrations. Improved sampling instructions and visual examination of the sample may minimize these risks. Salivary cortisone is essentially unaffected by the different preanalytical confounders and may be used as a first-line screening test for Cushing's syndrome.

Place, publisher, year, edition, pages
Bioscientifica, 2023
Keywords
Cushing’s syndrome, salivary cortisol, salivary cortisone, liquorice, sample contamination
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-208130 (URN)10.1530/ec-22-0324 (DOI)000971893300001 ()36383173 (PubMedID)2-s2.0-85151875249 (Scopus ID)
Funder
Region Västerbotten
Available from: 2023-05-10 Created: 2023-05-10 Last updated: 2024-03-26Bibliographically approved
Bäcklund, N., Brattsand, G., Lundstedt, S., Aardal, E., Bartuseviciene, I., Berinder, K., . . . Dahlqvist, P. (2023). Salivary cortisol and cortisone in diagnosis of Cushing's syndrome: a comparison of six different analytical methods. Clinical Chemistry and Laboratory Medicine, 61(10), 1780-1791
Open this publication in new window or tab >>Salivary cortisol and cortisone in diagnosis of Cushing's syndrome: a comparison of six different analytical methods
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2023 (English)In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 61, no 10, p. 1780-1791Article in journal (Refereed) Published
Abstract [en]

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Place, publisher, year, edition, pages
Walter de Gruyter, 2023
Keywords
Cushing's syndrome, immunoassay, LC-MS/MS, method comparison, salivary cortisol, salivary cortisone
National Category
Analytical Chemistry Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-206793 (URN)10.1515/cclm-2023-0141 (DOI)000964106600001 ()37013440 (PubMedID)2-s2.0-85151863068 (Scopus ID)
Funder
Region Västerbotten
Available from: 2023-04-24 Created: 2023-04-24 Last updated: 2024-03-26Bibliographically approved
Bäcklund, N., Brattsand, G., Israelsson, M., Ragnarsson, O., Burman, P., Edén Engström, B., . . . Dahlqvist, P. (2020). Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing's syndrome. European Journal of Endocrinology, 182(6), 569-582
Open this publication in new window or tab >>Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing's syndrome
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2020 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 182, no 6, p. 569-582Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Bioscientifica, 2020
National Category
Endocrinology and Diabetes Analytical Chemistry
Identifiers
urn:nbn:se:umu:diva-180275 (URN)10.1530/EJE-19-0872 (DOI)000626969000002 ()32213657 (PubMedID)2-s2.0-85084187749 (Scopus ID)
Available from: 2021-02-16 Created: 2021-02-16 Last updated: 2024-03-25Bibliographically approved
Israelsson, M., Brattsand, R. & Brattsand, G. (2018). 20α- and 20β-dihydrocortisone may interfere in LC-MS/MS determination of cortisol in saliva and urine. Annals of Clinical Biochemistry, 55(3), 341-347
Open this publication in new window or tab >>20α- and 20β-dihydrocortisone may interfere in LC-MS/MS determination of cortisol in saliva and urine
2018 (English)In: Annals of Clinical Biochemistry, ISSN 0004-5632, E-ISSN 1758-1001, Vol. 55, no 3, p. 341-347Article in journal (Refereed) Published
Abstract [en]

Background: LC-MS/MS methods offer high selectivity in cortisol determinations. However, endogenous steroid metabolites may still interfere and compromise the results, for example in the diagnosis of Cushing's syndrome. Erroneously elevated cortisol may, in particular, be misleading at the low concentrations found in salivary samples obtained at late night and after dexamethasone suppression.

Methods: Interferences in our LC-MS/MS method used for determination of cortisol in saliva and urine were identified by comparing their retention times and mass spectra with those of pure candidate substances. The chromatographic conditions used in our LC-MS/MS method, including column and mobile phase gradient, were varied in order to separate the target compound from the interferences.

Results: Two interferences, which were co-eluting or eluting close to cortisol in our original method, were successfully separated from cortisol by adjustment of the chromatographic conditions. These interferences were found in both urine and saliva and were identified as the two endogenous cortisol isomers 20- and 20-dihydrocortisone. The isomers share molecular mass and mass spectrometric fragmentation pattern with cortisol using electrospray ionization in the positive-ion mode. Both give rise to the transitions m/z 363.1>121.1, 363.1>115.1 and 363.1>97.1. In our original LC-MS/MS setup, the 20-dihydrocortisone co-eluted with cortisol in the chromatography step resulting in false high determinations.

Conclusions: Cortisol determination by LC-MS/MS may suffer from erroneously elevated results unless 20- and 20-dihydrocortisone are chromatographically separated from cortisol.

Place, publisher, year, edition, pages
Sage Publications, 2018
Keywords
cortisol, hydrocortisone, 20-dihydrocortisone, liquid chromatography-tandem mass spectrometry, liva, urine, Cushing's syndrome
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:umu:diva-148025 (URN)10.1177/0004563217724178 (DOI)000432043400003 ()28726485 (PubMedID)2-s2.0-85046773037 (Scopus ID)
Available from: 2018-05-30 Created: 2018-05-30 Last updated: 2024-03-25Bibliographically approved
Brattsand, G., Isaksson, A., Bjellerup, P. & Becker, C. (2018). Endokrina sjukdomar (10ed.). In: Elvar Theodorsson & Maria Berggren Söderlund (Ed.), Laurells Klinisk kemi i praktisk medicin: (pp. 283-344). Lund: Studentlitteratur AB
Open this publication in new window or tab >>Endokrina sjukdomar
2018 (Swedish)In: Laurells Klinisk kemi i praktisk medicin / [ed] Elvar Theodorsson & Maria Berggren Söderlund, Lund: Studentlitteratur AB, 2018, 10, p. 283-344Chapter in book (Refereed)
Place, publisher, year, edition, pages
Lund: Studentlitteratur AB, 2018 Edition: 10
National Category
Clinical Laboratory Medicine
Research subject
Clinical Chemistry
Identifiers
urn:nbn:se:umu:diva-154017 (URN)978-91-44-11974-8 (ISBN)
Available from: 2018-12-11 Created: 2018-12-11 Last updated: 2024-03-25Bibliographically approved
Li, A., Grönlund, E. & Brattsand, G. (2014). Automated white blood cell counts in cerebrospinal fluid using the body fluid mode on the platform Sysmex XE-5000. Scandinavian Journal of Clinical and Laboratory Investigation, 74(8), 673-680
Open this publication in new window or tab >>Automated white blood cell counts in cerebrospinal fluid using the body fluid mode on the platform Sysmex XE-5000
2014 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 74, no 8, p. 673-680Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The Sysmex XE-5000 offers automated quantification of red blood cells and white blood cells (WBCs) in body fluids, with differentiation of polymorphonuclear cells (PMNs) and mononuclear cells (MNCs). METHODS: We evaluated automated WBC counting in cerebrospinal fluid (CSF) using the body fluid mode on the Sysmex XE-5000, comparing it with flow cytometry as the reference method, and also with manual counting by microscopy. Experimental analysis for linearity and limit of detection was performed by diluting isolated WBCs in cell-free CSF. To study the ability to discriminate between PMNs and MNCs, samples were spiked using MNCs separated from peripheral blood. Comparison of WBC counts between a counting chamber and the XE-5000 was performed for 198 CSF samples. RESULTS: In the experimental set-up, within-run (CV 19%) and between-day imprecision (CV 15.3%) in quantitating total number of WBC on XE-5000 was acceptable for WBC counts >= 25x10(6)/L. Compared with expected cell counts, mean bias was +/- 2.6% for flow cytometry, +/- 5.5% for XE-5000 and -73.2% for manual counting. Differentiation between PMNs and MNCs was in concordance with flow cytometry. In comparisons of clinical CSF samples, overall agreement between the XE-5000 and manual counting was observed in 81% of the samples, but mean difference in WBC differentiation was higher for PMN (51.1x10(6)/L) than for MNC (7.95x10(6)/L). CONCLUSION: Despite limited precision at low WBC counts, XE-5000 could be a favourable alternative to the labour-intensive, time-consuming and less reliable manual counting and cuts turnaround times in routine CSF-based diagnosis.

Place, publisher, year, edition, pages
Informa Healthcare, 2014
Keywords
leukocyte count, neutrophils, monocyte, cerebrospinal fluid, automated exam
National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:umu:diva-97229 (URN)10.3109/00365513.2014.939994 (DOI)000344926400003 ()25180445 (PubMedID)2-s2.0-84908611644 (Scopus ID)
Available from: 2014-12-18 Created: 2014-12-12 Last updated: 2024-03-25Bibliographically approved
Brattsand, G., Nordin, G., Isaksson, A., Bjellerup, P., Stridsberg, M., Hård, L., . . . Larsson, K. (2012). Equalis/SFKK rekommenderar harmonisering av enheter vid hormonbestämningar för säkrare vård [Letter to the editor]. Läkartidningen, 109(39-40), 1773-1773
Open this publication in new window or tab >>Equalis/SFKK rekommenderar harmonisering av enheter vid hormonbestämningar för säkrare vård
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2012 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 39-40, p. 1773-1773Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Läkartidningen Förlag AB, 2012
National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:umu:diva-67080 (URN)23097890 (PubMedID)
Available from: 2013-03-12 Created: 2013-03-12 Last updated: 2024-03-25Bibliographically approved
Brattsand, G., Nordin, G., Isaksson, A., Bjellerup, P., Stridsberg, M., Hård, L., . . . Larsson, K. (2012). Equalis/SFKK rekommenderar harmonisering av enheter vid hormonbestämningar -Något också för Norden?. Klinisk Biokemi i Norden, 24(4), 20-27
Open this publication in new window or tab >>Equalis/SFKK rekommenderar harmonisering av enheter vid hormonbestämningar -Något också för Norden?
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2012 (Swedish)In: Klinisk Biokemi i Norden, ISSN 1101-2013, Vol. 24, no 4, p. 20-27Article in journal (Refereed) Published
Abstract [sv]

Equalis och Svensk Förening för Klinisk Kemi (SFKK) rekommenderar att de kliniska laboratorierna i Sverige använder enhetliga måttenheter vid hormonbestämningar för ökad jämförbarhet och patientsäkerhet. Vid analys i serum eller plasma med nuvarande metoder rekommenderas följande enheter:

• Adrenokortikotropt hormon (ACTH): pmol/L

• Insulin: mIE/L

• Parathormon (PTH): pmol/L

• Prolaktin: mIE/L

• Tillväxthormon (GH): μg/L

• Östradiol: pmol/L

• Aldosteron: pmol/L

• Reninkoncentration: mIE/L

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-71253 (URN)
Available from: 2013-05-23 Created: 2013-05-23 Last updated: 2024-03-25Bibliographically approved
Li, A. & Brattsand, G. (2011). Stability of serum samples and hemolysis interference on the high sensitivity troponin T assay: Letter to the editor. Clinical Chemistry and Laboratory Medicine, 49(2), 335-336
Open this publication in new window or tab >>Stability of serum samples and hemolysis interference on the high sensitivity troponin T assay: Letter to the editor
2011 (English)In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 49, no 2, p. 335-336Article in journal (Refereed) Published
Keywords
hemolysis, interference, stability, troponin T
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-40741 (URN)10.1515/CCLM.2011.035 (DOI)21077790 (PubMedID)
Available from: 2011-03-08 Created: 2011-03-08 Last updated: 2024-03-25Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-9474-6513

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