TSH reference intervals in adolescents in the iodine deficiency region. Comparison of direct and indirect approaches for estimating reference limits

Plekhanova O.S.

JSC Medsi Group;
Ural State Medical University

ORCID: 0000-0002-4271-0583

Tsvirenko S.V.

Ural State Medical University

ORCID: 0000-0003-0185-0050

Kiyaev A.V.

Ural State Medical University;
Regional Children Hospital

ORCID: 0000-0002-5578-5242

Saveliev L.I.

Ural State Medical University;
Regional Children Hospital;
Research Institute of Medical Cell Technologies

SPIN RSCI: 1427-5514
Scopus AuthorID: 55535477300
ORCID: 0000-0002-5180-6560

TSH reference intervals in adolescents in the iodine deficiency region. Comparison of direct and indirect approaches for estimating reference limits

Authors:

Plekhanova O.S., Tsvirenko S.V., Kiyaev A.V., Saveliev L.I.

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Journal: Laboratory Service. 2025;14(1): 21‑31

DOI: 10.17116/labs20251401121

Downloaded: 1

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To cite this article:

Plekhanova OS, Tsvirenko SV, Kiyaev AV, Saveliev LI. TSH reference intervals in adolescents in the iodine deficiency region. Comparison of direct and indirect approaches for estimating reference limits. Laboratory Service. 2025;14(1):21‑31. (In Russ.)
https://doi.org/10.17116/labs20251401121

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BACKGROUND

Due to the difficulties of recruiting reference groups for direct determination of reference intervals, methods for reference intervals calculating using laboratory database data have been proposed in the literature. At the moment, the properties and limitations of existing methods are not sufficiently described; for example, the issue of the influence of data from patients with established pathology, the results of which are within the RI limits, remains unresolved, including for skewed distributions of analytes.

THE AIM OF THE STUDY

Was to evaluate the possibilities of indirect methods for determining RI in adolescents for TSH in a population including the results from individuals with established thyroid pathology.

MATERIALS AND METHODS

The RI limits were calculated with indirect method using data from the entire database (all, n=1179, boys, n=542, girls, n=637), most of whose TSH pathological values were within the RI limits: TMC, RefineR, Kosmic, Bhattacharaya

RESULTS

The calculated limits by RefineR and TMC of the database TSH were verified. Results of calculating the simulated data were successful to varying degrees with different percentages and the distance of pathological data from the middle of the distribution of conditionally healthy individuals.

CONCLUSIONS

Results with conditionally pathological values that are within the RI limits can significantly affect the quality of RI limits calculations with indirect methods. The best way to calculate RI for TSH should be considered the TMC method as the one that best meets the criteria when calculating data from the database and when conducting simulation.

Keywords:

reference intervals

indirect calculation

indirect reference intervals

TSH

adolescents

Authors:

Plekhanova O.S.

JSC Medsi Group;
Ural State Medical University

ORCID: 0000-0002-4271-0583

Tsvirenko S.V.

Ural State Medical University

ORCID: 0000-0003-0185-0050

Kiyaev A.V.

Ural State Medical University;
Regional Children Hospital

ORCID: 0000-0002-5578-5242

Saveliev L.I.

Ural State Medical University;
Regional Children Hospital;
Research Institute of Medical Cell Technologies

SPIN RSCI: 1427-5514
Scopus AuthorID: 55535477300
ORCID: 0000-0002-5180-6560

Received:

17.02.2025

Accepted:

19.02.2025

List of references:

CLSI Document C28—A3c. Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline — third edition. Wayne, Pa., USA: CLSI; 2010.
ГОСТ Р ИСО 15189—2015. Медицинские лаборатории. Частные требования к качеству и компетенции. М. 2015.
ISO 15189-2015. Medical laboratories — Particular requirements for quality and competence. M. 2015. (In Russ.).
ГОСТ Р 53022.3—2008. Требования к качеству клинических лабораторных исследований. Часть 3. Правила оценки клинической информативности лабораторных тестов.
Clinical laboratory technologies. Requirements for quality of clin- ical laboratory tests. Part 3. Assessment of laboratory tests clinical significance. (In Russ.).
Evgina SA, Klimenkova OA, Plekhanova OS, Mayansky NA. Analysis of legal documents in the field of reference intervals. Laboratory Service. 2023;12(2):44-50. (In Russ.). https://doi.org/10.17116/labs20231202144
Plekhanova OS, Kalacheva OS, Saveliev LI, Moshkin AV. Sources of reference intervals used by laboratories. Survey results of 160 laboratories. Laboratory Service. 2023;12(2):7-14. (In Russ.) https://doi.org/10.17116/labs2023120217
Hoffmann RG. Statistics in the practice of medicine. JAMA. 1963;185:864-873.
Wosniok W, Haeckel R. A new indirect estimation of reference intervals: truncated minimum chi-square (TMC) approach. Clinical Chemistry and Laboratory Medicine (CCLM). 2019;57(12): 1933-1947. https://doi.org/10.1515/cclm-2018-1341
Holmes DT, Buhr KA. Widespread Incorrect Implementation of the Hoffmann Method, the Correct Approach, and Modern Alternatives. American Journal of Clinical Pathology. 2019;151(3): 328-336. https://doi.org/10.1093/ajcp/aqy149
Bhattacharya CG. A simple method of resolution of a distribution into Gaussian components. Biometrics. 1967;23:115-135. https://doi.org/10.2307/2528285
Ammer T, Schützenmeister A, Prokosch HU, Rauh M, Rank CM, Zierk J. RefineR: A Novel Algorithm for Reference Interval Estimation from Real-World Data. Sci Rep. 2021;11:16023. https://doi.org/10.1038/s41598-021-95301-2
Zierk J, Arzideh F, Kapsner LA, et al. Reference Interval Estima- tion from Mixed Distributions using Truncation Points and the Kolmogorov-Smirnov Distance (kosmic). Sci Rep. 2020;10:1704. Assessed december 2021. https://kosmic.diz.uk-erlangen.de/https://doi.org/10.1038/s41598-020-58749-2
Chesher D. Bellview: A tool to perform Bhattacharya analysis on lab oratory data. Accessed 4 February 2025.
Farrell CL, Nguyen L. Indirect Reference Intervals: Harnessing the Power of Stored Laboratory Data. Clin Biochem Rev. 2019;40(2):99-111. https://doi.org/10.33176/AACB-19-00022
Haeckel R, Wosniok W, Streichert T and Members of the Section Guide Limits of the DGKL, «Review of potentials and limitations of indirect approaches for estimating reference limits/intervals of quantitative procedures in laboratory medicine». Journal of Laboratory Medicine. 2021;45:2:35-53. https://doi.org/10.1515/labmed-2020-0131
Dirks N, den Elzen W, Hillebrand J, Jansen H, Boekel E, Brinkman J, Buijs M, Demir A, Dijkstra I, Endenburg S, Engbers P, Gootjes J, Janssen M, Kniest-de Jong W, Kok M, Kamphuis S, Kruit A, Michielsen E, Wolthuis A, Boelen A, & Heijboer A. Should we depend on reference intervals from manufacturer package inserts? Comparing TSH and FT4 reference intervals from four manufacturers with results from modern indirect methods and the direct method. Clinical Chemistry and Laboratory Medicine (CCLM). 2024;62(7):1352-1361. https://doi.org/10.1515/cclm-2023-1237
Kiyaev AV, Savelyev LI, Gerasimova LYu, Koroleva NP, Boyarsky SN, Tsirenko SV. The reference values of thyroid hormone and the prevalence of subclinical thyroid dysfunctions in adolescents in a mild iodine deficiency area. Problems of Endocrinology. 2008;54(4):14-17. (In Russ.). https://doi.org/10.14341/probl200854414-17
EFLM Biological Variation Database. Accessed February 1, 2025. https://biologicalvariation.eu
German Society of Clinical Chemistry and Laboratory Medicine. Decision limits/guideline values. Accessed 14 Feb 2025. https://www.dgkl.de/arbeitsgruppen/entscheidungsgrenzen-richtwerte
Henny J, Vassault A, Boursier G, Vukasovic I, Brguljan PM, Lohmander M. Recommendation for the review of biological reference intervals in medical laboratories. Clin Chem Lab Med. 2016;54:1893-1900.

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