Analytical bias of automated immunoassays for six serum steroid hormones
assessed by LC-MS/MS

Debeljak, Željko; Marković, Ivana; Pavela, Jasna; Lukić, Iva; Mandić, Dario; Mandić, Sanja; Horvat, Vesna; Šerić, Vatroslav

doi:10.11613/bm.2020.030701

Cited by 19 publications

(9 citation statements)

References 18 publications

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“…The limited agreement in aldosterone results between CLIA and LCSMS is evident. Whilst this poor correlation has been previously established ( 25 , 26 , 27 ), and we have noted a similar degree of discordance in our own laboratory in samples taken from patients without COVID-19 (unpublished data), the effect in COVID-19 patients is exaggerated. Solvent extraction significantly improves the correlation between methods suggesting a water-soluble metabolite may be cross-reacting in the direct immunoassay; this has also been previously demonstrated using extraction immunoassay ( 15 ).…”

Section: Discussionsupporting

confidence: 76%

See 1 more Smart Citation

Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay

Wiegand

Halsall

Cowan

et al. 2022

Endocrine Connections

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Objective: Previous studies have reported conflicting findings regarding aldosterone levels in patients hospitalised with COVID-19. We therefore used the gold-standard technique of liquid chromatography tandem mass-spectrometry (LCMSMS) to address this uncertainty. Design: All patients admitted to Addenbrooke’s Hospital Cambridge with COVID-19 between March 10, 2020 and May 13, 2021, and in whom a stored blood sample was available for analysis, were eligible for inclusion. Methods: Aldosterone was measured by LCMSMS and by immunoassay; cortisol and renin were determined by immunoassay. Results: Using LCMSMS, aldosterone was below the limit of detection (<70 pmol/L) in 74 (58.7%) patients. Importantly, this finding was discordant with results obtained using a commonly employed clinical immunoassay (Liaison Diasorin®), which over-estimated aldosterone compared to the LCMSMS assay (intercept 14.1 [95% CI -34.4 to 54.1] + slope 3.16 [95% CI 2.09 to 4.15] pmol/L). The magnitude of this discrepancy did not clearly correlate with markers of kidney or liver function. Solvent extraction prior to immunoassay improved the agreement between methods (intercept -14.9 [95% CI -31.9 to -4.3] and slope 1.0 [95% CI 0.89 to 1.02] pmol/L) suggesting the presence of a water-soluble metabolite causing interference in the direct immunoassay. We also replicated a previous finding that blood cortisol concentrations were often increased, with increased mortality in the group with serum cortisol levels >744 nmol/L (p=0.005). Conclusion: When measured by LCMSMS, aldosterone was found to be profoundly low in a significant proportion of patients with COVID-19 at the time of hospital admission. This has likely not been detected previously due to high levels of interference with immunoassays in patients with COVID-19, and this merits further prospective investigation.

show abstract

Section: Discussionsupporting

confidence: 76%

“…The limited agreement in aldosterone results between CLIA and LCSMS is evident. Whilst this poor correlation has been previously established [25][26][27],…”

Section: Discussionmentioning

confidence: 82%

Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay

Wiegand

Halsall

Cowan

et al. 2022

Endocrine Connections

View full text Add to dashboard Cite

show abstract

“…The limited agreement in aldosterone results between CLIA and LCSMS is evident. Whilst this poor correlation has been previously established [24, 25], the effect in COVID-19 patients is exaggerated. Solvent extraction significantly improves the correlation between methods suggesting a water soluble metabolite may be cross reacting in the direct immunoassay; this has also been previously demonstrated using extraction immunoassay [15].…”

Section: Discussionmentioning

confidence: 76%

Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay

Wiegand

Halsall

Cowan

et al. 2022

Preprint

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ObjectivePrevious studies have reported conflicting findings regarding aldosterone levels in patients hospitalised with COVID-19. We therefore used the gold-standard technique of liquid chromatography tandem mass-spectrometry (LCMSMS) to address this uncertainty.DesignAll patients admitted to Cambridge University Hospitals with COVID-19 between March 10, 2020 and May 13, 2021, and in whom a stored blood sample was available for analysis, were eligible for inclusion.MethodsAldosterone was measured by LCMSMS and by immunoassay; cortisol and renin were determined by immunoassay.ResultsUsing LCMSMS, aldosterone was below the limit of detection (<70 pmol/L) in 74 (58.7%) patients. Importantly, this finding was discordant with results obtained using a commonly employed clinical immunoassay (Liaison Diasorin®), which over-estimated aldosterone compared to the LCMSMS assay (intercept 14.1 [95% CI -34.4 to 54.1] + slope 3.16 [95% CI 2.09 to 4.15] pmol/L). The magnitude of this discrepancy did not clearly correlate with markers of kidney or liver function. Solvent extraction prior to immunoassay improved the agreement between methods (intercept -14.9 [95% CI -31.9 to -4.3] and slope 1.0 [95% CI 0.89 to 1.02] pmol/L) suggesting the presence of a water-soluble metabolite causing interference in the direct immunoassay. We also replicated a previous finding that blood cortisol concentrations were often increased, with increased mortality in the group with serum cortisol levels >744 nmol/L (p=0.005).ConclusionWhen measured by LCMSMS, aldosterone was found to be profoundly low in a significant proportion of patients with COVID-19 at the time of hospital admission. This has likely not been detected previously due to high levels of interference with immunoassays in patients with COVID-19, and this merits further prospective investigation.

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“…On the other hand, in our study LC–MS/MS was used. LC–MS/MS has some advantages over the immunoassays used in earlier studies: thanks to the chromatographic separation and selectivity of mass spectrometry, LC–MS/MS is not so prone to interferences produced by the related compounds that may exist in maternal serum 27,28 . Significant analytical bias was detected for a number of different steroid hormone concentrations, including DHEA‐S, assessed by immunoassays.…”

Section: Discussionmentioning

confidence: 99%

Requirement for oxytocin augmentation in spontaneous parturition is associated with the maternal serum steroid hormones assessed by liquid chromatography coupled to the tandem mass spectrometry

Kadivnik

Debeljak

Mandić

et al. 2021

J of Obstet and Gynaecol

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Aim The aim of research was to evaluate the maternal serum concentration of selected endogenous steroid hormones during spontaneous parturition at term and to determinate their association with the need for oxytocin augmentation. Methods Blood of 108 healthy pregnant women whose parturition started with the regular spontaneous uterine contractions was drawn at the beginning of the labor. Liquid chromatography coupled to the tandem mass spectrometry device was utilized for measurement of sex hormone binding globulin, aldosterone, androstenedione, cortisol, cortisone, corticosterone, dehydroepiandrosterone, dehydroepiandrosteron sulphate, 17‐hydroxyprogesterone, progesterone, and testosterone. Mann–Whitney U test, chi‐square test, univariate and multivariate logistic regression, and receiver operating characteristic (ROC) analysis were used for the data analysis. Results Reference ranges of the selected hormones assessed by liquid chromatography coupled to the tandem mass spectrometry in maternal serum were established. Statistically significant differences in the serum concentration of corticosterone, dehydroepiandrosterone, and androstenedione between mothers requiring oxytocin augmentation and the rest of women having spontaneous parturition were found (p = 0.002, p = 0.008, and p = 0.04, respectively). Concentrations were lower in the group of mothers who required oxytocin infusion for progression of labor. ROC analysis showed that all the mothers with dehydroepiandrosterone serum concentration above 21.6 nmol/L have lower chance to use oxytocin infusion for the labor progression ( area under the curve (AUC) = 0.649, sensitivity = 71.7%, specificity = 59.6%, p = 0.006). Conclusion This research provided reference ranges for the selected maternal serum steroid hormones at the beginning of parturition. Association of corticosterone, dehydroepiandrosterone, and androstenedione with the need for the oxytocin infusion usage has been established. Dehydroepiandrosterone could be potential predictor of oxytocin infusion augmentation for progression of the parturition.

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Analytical bias of automated immunoassays for six serum steroid hormones assessed by LC-MS/MS

Cited by 19 publications

References 18 publications

Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay

Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay

Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay

Requirement for oxytocin augmentation in spontaneous parturition is associated with the maternal serum steroid hormones assessed by liquid chromatography coupled to the tandem mass spectrometry

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