Biological Variation of Thyroid Stimulating Hormone, Free Triiodothyronine and Free Thyroxine in Healthy Subjects in Turkey

Overview

Journal Biochem Med (Zagreb)

Specialty Biochemistry

Date 2025 Feb 20

PMID 39974197

Authors

Raziye Yildiz

Hayat Ozkanay

Fatma Demet Arslan

Mehmet Koseoglu

Affiliations

Soon will be listed here.

Abstract

Introduction: Biological variation (BV) data are necessary for interpretation of test results and assessment of analytical performance. We aimed to determine the BV estimates for thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine(fT4) in healthy subjects in Turkey and compare them with the literature findings.

Materials And Methods: A total of 21 Turkish healthy volunteers (12 males and 9 females) were included in the study. Blood samples were collected once a week for five weeks, and the analysis was performed using the chemiluminescent immunoassay method on an Advia Centaur XP (Siemens Diagnostic, Tarrytown, USA). Analytical variation (CV), within-subject BV (CV) and between-subject BV (CV) were calculated. Analytical goals, individuality index (II) and reference change value (RCV) were derived from these data. Statistical analysis was performed using BioVar: BV analysis tool v.1.0.

Results: For TSH, fT3 and fT4, CV (confidence interval, CI) were 3.3% (2.9 to 3.8), 1.7% (1.5 to 1.9) and 2.7% (2.4 to 3.1); CV (CI) were 22.3% (19.3 to 26.3), 4.4% (3.8 to 5.3) and 5.1% (4.3 to 6.1); CV (CI) were 26.6% (19.2 to 39.8), 9.2% (6.9 to 13.6) and 8.2% (6.1 to 12.1), respectively. For TSH, fT3 and fT4, desirable total errors were 27.1%, 6.2% and 6.6%; II values were calculated as 0.84, 0.48 and 0.61; and RCV% values (decrease; increase) were - 40.3;67.6, - 10.4;11.6 and - 12.7;14.5, respectively.

Conclusions: Our study provides updated BV data for thyroid function tests (TFTs) in healthy subjects in Turkey. As TFTs have shown a high degree of individuality, RCV should be preferred rather than population-based reference ranges in the assessment of serum concentrations. Our BV estimates were compatible with European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) BV meta-analysis data obtained using different immunoassay methods in different populations.

References

Bartlett W, Braga F, Carobene A, Coskun A, Prusa R, Fernandez-Calle P . A checklist for critical appraisal of studies of biological variation. Clin Chem Lab Med. 2015; 53(6):879-85. DOI: 10.1515/cclm-2014-1127. View

Yamada S, Horiguchi K, Akuzawa M, Sakamaki K, Shimomura Y, Kobayashi I . Seasonal Variation in Thyroid Function in Over 7,000 Healthy Subjects in an Iodine-sufficient Area and Literature Review. J Endocr Soc. 2022; 6(6):bvac054. PMC: 9070835. DOI: 10.1210/jendso/bvac054. View

Carobene A, Franzini C, Ceriotti F . Comparison of the results from two different External Quality Assessment Schemes supports the utility of robust quality specifications. Clin Chem Lab Med. 2011; 49(7):1143-9. DOI: 10.1515/CCLM.2011.196. View

Carobene A, Strollo M, Jonker N, Barla G, Bartlett W, Sandberg S . Sample collections from healthy volunteers for biological variation estimates' update: a new project undertaken by the Working Group on Biological Variation established by the European Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem Lab Med. 2016; 54(10):1599-608. DOI: 10.1515/cclm-2016-0035. View

Ricos C, Arbos M . Quality goals for hormone testing. Ann Clin Biochem. 1990; 27 ( Pt 4):353-8. DOI: 10.1177/000456329002700412. View

Fernandez-Calle P, Diaz-Garzon J, Bartlett W, Sandberg S, Braga F, Beatriz B . Biological variation estimates of thyroid related measurands - meta-analysis of BIVAC compliant studies. Clin Chem Lab Med. 2021; 60(4):483-493. DOI: 10.1515/cclm-2021-0904. View

Liu Y, Cao Y, Liu X, Wu L, Cai W . Evaluation of the analytical performance of endocrine analytes using sigma metrics. J Clin Lab Anal. 2020; 35(1):e23581. PMC: 7843286. DOI: 10.1002/jcla.23581. View

Vanderpump M . The epidemiology of thyroid disease. Br Med Bull. 2011; 99:39-51. DOI: 10.1093/bmb/ldr030. View

Aarsand A, Roraas T, Fernandez-Calle P, Ricos C, Diaz-Garzon J, Jonker N . The Biological Variation Data Critical Appraisal Checklist: A Standard for Evaluating Studies on Biological Variation. Clin Chem. 2017; 64(3):501-514. DOI: 10.1373/clinchem.2017.281808. View

10.

Ankrah-Tetteh T, Wijeratne S, Swaminathan R . Intraindividual variation in serum thyroid hormones, parathyroid hormone and insulin-like growth factor-1. Ann Clin Biochem. 2008; 45(Pt 2):167-9. DOI: 10.1258/acb.2007.007103. View

11.

Yildiz Z, Dagdelen L . Reference intervals for thyroid disorders calculated by indirect method and comparison with reference change values. Biochem Med (Zagreb). 2023; 33(1):010704. PMC: 9807239. DOI: 10.11613/BM.2023.010704. View

12.

Andersen S, Pedersen K, Bruun N, Laurberg P . Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab. 2002; 87(3):1068-72. DOI: 10.1210/jcem.87.3.8165. View

13.

Polo Polo M, Ricos Aguila C, Catalan Gili R, Juvany Roig R . [Clinical application of the biological variability data of the thyroid hormones]. Med Clin (Barc). 1992; 99(14):529-31. View

14.

Emre H, Karpuzoglu F, Coskun C, Sezer E, Ozturk O, Ucar F . Utilization of biological variation data in the interpretation of laboratory test results - survey about clinicians' opinion and knowledge. Biochem Med (Zagreb). 2020; 31(1):010705. PMC: 7745156. DOI: 10.11613/BM.2021.010705. View

15.

Vasileiou M, Gilbert J, Fishburn S, Boelaert K . Thyroid disease assessment and management: summary of NICE guidance. BMJ. 2020; 368:m41. DOI: 10.1136/bmj.m41. View

16.

Maes M, Mommen K, Hendrickx D, Peeters D, DHondt P, Ranjan R . Components of biological variation, including seasonality, in blood concentrations of TSH, TT3, FT4, PRL, cortisol and testosterone in healthy volunteers. Clin Endocrinol (Oxf). 1997; 46(5):587-98. DOI: 10.1046/j.1365-2265.1997.1881002.x. View

17.

Coskun A, Sandberg S, Unsal I, Cavusoglu C, Serteser M, Kilercik M . Personalized Reference Intervals in Laboratory Medicine: A New Model Based on Within-Subject Biological Variation. Clin Chem. 2020; 67(2):374-384. DOI: 10.1093/clinchem/hvaa233. View

18.

Mairesse A, Wauthier L, Courcelles L, Luyten U, Burlacu M, Maisin D . Biological variation and analytical goals of four thyroid function biomarkers in healthy European volunteers. Clin Endocrinol (Oxf). 2020; 94(5):845-850. DOI: 10.1111/cen.14356. View

19.

Van Uytfanghe K, Ehrenkranz J, Halsall D, Hoff K, Loh T, Spencer C . Thyroid Stimulating Hormone and Thyroid Hormones (Triiodothyronine and Thyroxine): An American Thyroid Association-Commissioned Review of Current Clinical and Laboratory Status. Thyroid. 2023; 33(9):1013-1028. PMC: 10517335. DOI: 10.1089/thy.2023.0169. View

20.

Bottani M, Aarsand A, Banfi G, Locatelli M, Coskun A, Diaz-Garzon J . European Biological Variation Study (EuBIVAS): within- and between-subject biological variation estimates for serum thyroid biomarkers based on weekly samplings from 91 healthy participants. Clin Chem Lab Med. 2021; 60(4):523-532. DOI: 10.1515/cclm-2020-1885. View