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. 2022 Jan 7;17(1):e0261715.
doi: 10.1371/journal.pone.0261715. eCollection 2022.

Establishing laboratory-specific reference intervals for TSH and fT4 by use of the indirect Hoffman method

Sylwia Płaczkowska  1 , Małgorzata Terpińska  1   2 , Agnieszka Piwowar  3
Affiliations

Establishing laboratory-specific reference intervals for TSH and fT4 by use of the indirect Hoffman method

Sylwia Płaczkowska et al. PLoS One. .

Abstract

Background: The results of examinations of laboratory parameters are the basis of appropriate medical decisions. The availability of reliable and accurate reference intervals (RIs) for each laboratory parameter is an integral part of its appropriate interpretation. Each medical laboratory should confirm their RIs. Up-to-date reference intervals for thyroid function hormones are still a matter of ongoing controversy. The aim of the study was the application of the indirect Hoffman method to determine RIs for TSH and fT4 based on the large data pools stored in laboratory information systems and the comparison of these RIs to generally used RIs.

Material and methods: The TSH and fT4 routine examination results of hospitalized and outpatient populations were collected over five years (2015-2019), and reference limits were established by the improved Hoffmann method after the exclusion of outliers. Comparative verification of established RIs was conducted with the RIs values provided by test manufacturers and literature data.

Results: Various RIs were observed in different age groups in the examined populations. For TSH, RIs varied between different age groups, with a narrower range of RIs in the studied adult population and a shift of both reference boundaries toward higher values in comparison to manufacturers' data among children. RIs estimated for fT4 were very similar to the manufacturer and literature data.

Conclusion: Thyroid hormone levels change during a person's lifetime and vary between sexes, but this difference does not always influence the clinical interpretation of laboratory results in the context of RIs. The use of indirect methods is justified due to the ease and low cost of their application.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Number of outliers excluded from the entire data base by the two-sided Tuckey test (1.5IQR) for each studied age group.
Fig 2
Fig 2. A representative Q-Q plot of distribution of lnTSH for participants aged ≥18 and <40.
Fig 3
Fig 3
RIs for TSH (panel A) and fT4 (panel B) in all participants included in the analysis groups and among males and females in each age group.
See this image and copyright information in PMC

References

    1. Ozarda Y. Reference intervals: Current status, recent developments and future considerations. Vol. 26, Biochemia Medica. Biochemia Medica, Editorial Office; 2016. p. 5–16. doi: 10.11613/BM.2016.001 - DOI - PMC - PubMed
    1. CLSI and IFCC. C28-A3 document; Defining, establishing and verifying reference intervals in the clinical laboratory: approved guideline-third edition, 2008;28:1–76.
    1. Jones GRD, Haeckel R, Loh TP, Sikaris K, Streichert T, Katayev A, et al.. Indirect methods for reference interval determination–review and recommendations. Clin Chem Lab Med [Internet]. 57(1):20–9. doi: 10.1515/cclm-2018-0073 - DOI - PubMed
    1. Barth JH, Spencer JD, Goodall SR, Luvai A. Reference intervals for thyroid hormones on Advia Centaur derived from three reference populations and a review of the literature. Ann Clin Biochem [Internet]. 2016. Apr 5;53(3):385–9. doi: 10.1177/0004563216636897 - DOI - PubMed
    1. Lo Sasso B, Vidali M, Scazzone C, Agnello L, Ciaccio M. Reference interval by the indirect approach of serum thyrotropin (TSH) in a Mediterranean adult population and the association with age and gender. Clin Chem Lab Med [Internet]. 2019. Sep 25 [cited 2020 Nov 4];57(10):1587–94. doi: 10.1515/cclm-2018-0957 - DOI - PubMed