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Verification of sex- and age-specific reference intervals for 13 serum steroids determined by mass spectrometry: evaluation of an indirect statistical approach

  • Sophie C. Anker EMAIL logo , Jakob Morgenstern , Jakob Adler , Maik Brune , Sebastian Brings , Thomas Fleming , Elisabeth Kliemank , Markus Zorn , Andreas Fischer , Julia Szendroedi , Lars Kihm and Johanna Zemva
Published/Copyright: December 20, 2022
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 61 Issue 3

Abstract

Objectives

Conventionally, reference intervals are established by direct methods, which require a well-characterized, obviously healthy study population. This elaborate approach is time consuming, costly and has rarely been applied to steroid hormones measured by mass spectrometry. In this feasibility study, we investigate whether indirect methods based on routine laboratory results can be used to verify reference intervals from external sources.

Methods

A total of 11,259 serum samples were used to quantify 13 steroid hormones by mass spectrometry. For indirect estimation of reference intervals, we applied a “modified Hoffmann approach”, and verified the results with a more sophisticated statistical method (refineR). We compared our results with those of four recent studies using direct approaches.

Results

We evaluated a total of 81 sex- and age-specific reference intervals, for which at least 120 measurements were available. The overall agreement between indirectly and directly determined reference intervals was surprisingly good as nearly every fourth reference limit could be confirmed by narrow tolerance limits. Furthermore, lower reference limits could be provided for some low concentrated hormones by the indirect method. In cases of substantial deviations, our results matched the underlying data better than reference intervals from external studies.

Conclusions

Our study shows for the first time that indirect methods are a valuable tool to verify existing reference intervals for steroid hormones. A simple “modified Hoffmann approach” based on the general assumption of a normal or lognormal distribution model is sufficient for screening purposes, while the refineR algorithm may be used for a more detailed analysis.

Keywords: liquid-chromatography; liquid–liquid-extraction; mass spectrometry; reference intervals; steroids
Corresponding author: Sophie C. Anker, Department of Internal Medicine I and Clinical Chemistry, University Hospital Heidelberg, Heidelberg, Germany, E-mail:
Sophie C. Anker and Jakob Morgenstern have contributed equally to this work.

  1. Research funding: Non-declared.

  2. Author contribution: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the responsible Ethics Board of the Medical Faculty of the University of Heidelberg (S-566/2021).

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2022-0603).

Received: 2022-06-22
Accepted: 2022-11-16
Published Online: 2022-12-20
Published in Print: 2023-02-23

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2022-0603
Keywords for this article
liquid-chromatography; liquid–liquid-extraction; mass spectrometry; reference intervals; steroids

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Cell population data: much more to explore
  4. Reviews
  5. Differences between high-sensitivity cardiac troponin T and I in stable populations: underlying causes and clinical implications
  6. Choosing which in-hospital laboratory tests to target for intervention: a scoping review
  7. Opinion Papers
  8. Definitions and major prerequisites of direct and indirect approaches for estimating reference limits
  9. An algorithm for PCT-guided antimicrobial therapy: a consensus statement by Japanese experts
  10. General Clinical Chemistry and Laboratory Medicine
  11. The usefulness of implementing minimum retest intervals in reducing inappropriate laboratory test requests in a Dutch hospital
  12. Using three external quality assurance schemes to achieve equivalent international normalized ratio results in primary and secondary healthcare
  13. Optimizing the screening of alpha-1 antitrypsin deficiency using serum protein electrophoresis
  14. Anti-Ki/anti-PA28γ autoantibodies contribute to the HEp-2 indirect immunofluorescence nuclear speckled pattern
  15. Simultaneous quantification of tryptophan metabolites by liquid chromatography tandem mass spectrometry during early human pregnancy
  16. Reference Values and Biological Variations
  17. Verification of sex- and age-specific reference intervals for 13 serum steroids determined by mass spectrometry: evaluation of an indirect statistical approach
  18. Cancer Diagnostics
  19. Mucin 13 (MUC13) as a candidate biomarker for ovarian cancer detection: potential to complement CA125 in detecting non-serous subtypes
  20. Increased levels of N6-methyladenosine in peripheral blood RNA: a perspective diagnostic biomarker and therapeutic target for non-small cell lung cancer
  21. Cardiovascular Diseases
  22. Diagnostic utility of total NT-proBNP testing by immunoassay based on antibodies targeting glycosylation-free regions of NT-proBNP
  23. Infectious Diseases
  24. Serial measurement of circulating calprotectin as a prognostic biomarker in COVID-19 patients in intensive care setting
  25. Evaluation of ichroma™ COVID-19 interferon gamma release assay for detection of vaccine-induced immunity in healthcare workers
  26. Application of ultrasensitive assay for SARS-CoV-2 antigen in nasopharynx in the management of COVID-19 patients with comorbidities during the peak of 2022 Shanghai epidemics in a tertiary hospital
  27. Developing a machine learning prediction algorithm for early differentiation of urosepsis from urinary tract infection
  28. Letters to the Editor
  29. A panhaemocytometric approach to COVID-19: the importance of cell population data on Sysmex XN-series analysers in severe disease
  30. Critical appraisal of “choosing which in-hospital laboratory tests to target for intervention: a scoping review”
  31. What is the best external quality control sample for your laboratory?
  32. Pre-analytical variability of the Lumipulse immunoassay for plasma biomarkers of Alzheimer’s disease
  33. Biological variation of serum iron from the European biological variation study (EuBIVAS)
  34. Tube shaking and pneumatic transportation: impact on presepsin concentrations measured by both fully automated and POCT analyzers
  35. Endogenous isobaric interference on serum 17 hydroxyprogesterone by liquid chromatography-tandem mass spectrometry methods
  36. A simulation model for organization and management skills assessment that meets ISO 15189
  37. Congress Abstracts
  38. Annual meeting of the Royal Belgian Society of Laboratory Medicine: “Men’s health”
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