The effect of serum matrix and gender on cortisol measurement by commonly used immunoassays
Abstract
Background: Considerable intermethod bias has been observed between cortisol immunoassays, with some also displaying a gender difference. Cortisol immunoassay performance is affected by serum matrix effects such as changes in steroid binding proteins and presence of interfering steroids which can be altered in various clinical settings. This study investigates cortisol immunoassay bias in pregnancy, renal failure and intensive care patients. Methods: Serum remaining after routine analysis from pregnant patients, patients on the intensive care unit and patients with renal failure were obtained prior to disposal and used to create 20 anonymous samples per group. A male and female serum pool was prepared and spiked with cortisol. Samples were aliquoted and distributed to four hospitals for cortisol analysis by immunoassays from four different manufacturers. Cortisol was also measured by an isotope dilution-gas chromatography–mass spectrometry method for comparison of assay bias. Results: Differences in cortisol immunoassay bias were observed across the different patient groups. A negative bias compared to pooled serum samples was observed for pregnancy serum, whilst a more positive bias was seen in renal failure and intensive care patients. Variation in bias was greatest in renal failure with the Roche E170 the most affected and the Abbott architect the least (interquartile ranges 44% and 14%, respectively). Conclusions: Cortisol immunoassay bias may be affected by gender and differences in serum matrix from patients with various clinical conditions. Users of cortisol assays should be aware of differing matrix effects on their assay and the relevance of these for the interpretation of clinical results.
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Immunoassays are often limited by cross-reactivities, matrix effects, and high measurement uncertainty at low concentrations.
“IAs have advantages such as small sample volumes, high degree of automation, quick turnover times and a relatively low cost, but are often limited by cross-reactivities, matrix effects and high measurement uncertainty at low concentrations [6,7].”
From Salivary cortisol and cortisone in diagnosis of Cushing's syndrome: a comparison of six different analytical methods (2023) · cites this paper as [7]
Immunoassays have advantages including small sample volumes, high automation, quick turnover, and relatively low cost.
“IAs have advantages such as small sample volumes, high degree of automation, quick turnover times and a relatively low cost, but are often limited by cross-reactivities, matrix effects and high measurement uncertainty at low concentrations [6,7].”
From Salivary cortisol and cortisone in diagnosis of Cushing's syndrome: a comparison of six different analytical methods (2023) · cites this paper as [7]
Commercial immunoassays are prone to sex-specific biases and matrix effects in selected patient groups when compared with a GC-MS reference measurement procedure.
“Comparisons of cortisol results to a GC-MS reference measurement procedure (RMP) have previously demonstrated that commercial immunoassays are prone to both sex-specific biases and matrix effects in select patient populations (8 ).”
From Serum cortisol: an up-to-date assessment of routine assay performance (2016) · cites this paper as [8]
This study benefits from using single donor samples for comparison, providing a true representation of each assay's performance for individual samples.
“In contrast to EQA schemes and previous studies (8 ), this study benefits from using single donor samples for comparison.Although pooling samples can provide sufficient volume for large-scale studies, it can also alter the sample matrix and potentially bias results.Our approach instead provides a true representation of the performance of each assay for individual samples.”
From Serum cortisol: an up-to-date assessment of routine assay performance (2016) · cites this paper as [8]
Previous work speculated that cortisol underrecovery may be attributed to increased cortisol-binding globulin concentrations secondary to pregnancy or oral contraceptive pill medication.
“Previous work has speculated that cortisol underrecovery may be attributed to increased CBG concentra-tions secondary to pregnancy (8 ) or OCP medication (9 ).”
From Serum cortisol: an up-to-date assessment of routine assay performance (2016) · cites this paper as [8]
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- Authors
- Dodd, A., Ducroq, D., Neale, S., Wise, M., Mitchem, K., Armston, A., Barth, J., El-Farhan, N., Rees, D., & Evans, C.
- Affiliations
- Department of Medical Biochemistry and Immunology, University Hospital of Wales, Cardiff, UK
- Quality Laboratory, WEQAS, Cardiff, UK
- University Hospital of Wales (GB)
- Adult Critical Care, University Hospital of Wales, Cardiff, UK
- Department of Clinical Biochemistry, Prince Charles Hospital, Merthyr Tydfil, UK
- University Hospital Southampton NHS Foundation Trust (GB)
- Blood Sciences, Old Medical School, Leeds Teaching Hospitals Trust, Leeds, UK
- Department of Medicine, Royal Gwent Hospital, Newport, UK
- Centre for Endocrine and Diabetes Sciences, School of Medicine, Cardiff University, Cardiff, UK
- ORCID
- Evans, C
- Venue
- Annals of Clinical Biochemistry: International Journal of Laboratory Medicine
- Publisher
- SAGE Publications
- Published
- 2013-12-20
- Volume
- 51
- Issue
- 3
- Pages
- 379-385
- ISSN
- 0004-5632 (ISSN-L)
- 1758-1001
- OpenAlex
- W2039920314
- Cited by
- 34
- References
- 9
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 4 · 2022: 3 · 2020: 4 · 2018: 2 · 2017: 6 · 2016: 2 · 2015: 4 · 2014: 4
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Clinical Biochemistry International Journal of Laboratory Medicine (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- cortisol, gender differences, pregnancy, renal failure, intensive care unit patients, steroid binding proteins, Abbott Architect
- MeSH terms
- Blood Chemical Analysis, Female, Humans, Hydrocortisone, Immunoassay, Male, Pregnancy, Sex Factors
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