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Cited by 12Stress Responses and CortisolClinical Laboratory Practices and Quality ControlAdrenal Hormones and Disorders

Confounding effects of liquorice, hydrocortisone, and blood contamination on salivary cortisol but not cortisone

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Imamovic, Marcus, Bäcklund, Nils, Lundstedt, Staffan, Brattsand, Göran, Aardal, Elisabeth, Olsson, Tommy, Dahlqvist, Per·2023·Endocrine Connections
DOI 10.1530/ec-22-0324PMC PMC9782436
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Abstract

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.

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  • Salivary cortisone has been shown to correlate better with plasma free cortisol than salivary cortisol and to be less susceptible to preanalytical confounders.

    “Salivary cortisone has been shown to correlate better with plasma free cortisol than salivary cortisol and to be less susceptible to preanalytical confounders (20, 23, 27, 28).”

    From Salivary Cortisol and Cortisone Can Circumvent Confounding Effects of Oral Contraceptives in the Short Synacthen Test (2024) · cites this paper as [27]

    The Discussion (page unavailable) says salivary cortisone is essentially unaffected by the preanalytical confounders studied—liquorice, blood contamination, and topical hydrocortisone—while salivary cortisol may be falsely elevated. The paper does not report that salivary cortisone correlates better with plasma free cortisol than salivary cortisol; searches for that comparison found no supporting passage. (LLM, conf=0.86)

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  • Salivary cortisone may have an advantage over salivary cortisol as a diagnostic analyte, since it is considerably more robust against confounding factors including blood contamination, topical hydrocortisone, and licorice consumption.

    “Salivary cortisone may have an advantage over salivary cortisol as a diagnostic analyte, since it is considerably more robust against confounding factors including blood contamination, topical hydrocortisone, and licorice consumption (23, 27).”

    From Salivary Cortisol and Cortisone Can Circumvent Confounding Effects of Oral Contraceptives in the Short Synacthen Test (2024) · cites this paper as [27]

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Cited by

Sorted by citations

Authors
Imamovic, M., Bäcklund, N., Lundstedt, S., Brattsand, G., Aardal, E., Olsson, T., & Dahlqvist, P.
Affiliations
  • Umeå University (SE)
  • Linköping University (SE)
Corresponding author
Imamovic, Marcus
ORCID
Venue
Endocrine Connections
Publisher
Bioscientifica
Published
2023-01-01
Volume
12
Issue
1
ISSN
2049-3614 (ISSN-L)
DOI
10.1530/ec-22-0324
PMC
PMC9782436
OpenAlex
W4309163895
Cited by
12
References
12
Citations by year
2026: 4 · 2025: 1 · 2024: 4 · 2023: 3
FWCI
1.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Endocrine Connections (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Västerbotten Läns Landsting
  • Umeå Universitet
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
salivary cortisol, salivary cortisone, licorice, topical hydrocortisone, blood contamination, cortisol/cortisone ratio, saliva sampling

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