The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Login
EN
+7 (495) 482-4118
+7 (495) 482-0604
+8 800 250-18-12
  • (toll-free number for subscriptions)
    Mon-Fri from 10 a.m. to 6 p.m.

  • © 1998-2025
+7 (495) 482-43-29
EN
All journals
Journal
Year
Year
Search result: 0

Dirks N.F.

W.P.J. den Elzen

Hillebrand J.J.

Jansen H.I.

ten Boekel E.

Brinkman J.

Buijs M.M.

Demir A.Y.

Dijkstra I.M.

Endenburg S.C.

Engbers P.

Gootjes J.

M.J.W. Janssen

W.H.A. Kniest-de Jong

Kok M.B.

Kamphuis S.

Kruit A.

Michielsen E.

Wolthuis A.

Boelen A.

Heijboer A.C.

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

Authors:

Dirks N.F., W.P.J. den Elzen, Hillebrand J.J., Jansen H.I., ten Boekel E., Brinkman J., Buijs M.M., Demir A.Y., Dijkstra I.M., Endenburg S.C., Engbers P., Gootjes J., M.J.W. Janssen, W.H.A. Kniest-de Jong, Kok M.B., Kamphuis S., Kruit A., Michielsen E., Wolthuis A., Boelen A., Heijboer A.C.

More about the authors

Journal: Laboratory Service. 2024;13(3): 50‑60

DOI: 10.17116/labs20241303150

Views: 285

Downloaded: 4

Buy for 300₽
Contact the author
Table of contents

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
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

To cite this article:

Dirks NF, WPJ den Elzen, Hillebrand JJ, et al. . 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. Laboratory Service. 2024;13(3):50‑60. (In Russ.)
https://doi.org/10.17116/labs20241303150

 
Подписка 2025-2 (Laboratory Service)
МСФ на ЯМ
Close metadata
Recommended articles:
TSH refe­rence inte­rvals in adolescents in the iodine defi­ciency region. Comparison of direct and indi­rect approaches for esti­mating refe­rence limits. Labo­ratory Service. 2025;(1):21-31

OBJECTIVE

Correct interpretation of thyroid function tests relies on correct reference intervals (RIs) for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). ISO15189 mandates periodic verification of RIs, but laboratories struggle with cost-effective approaches. We investigated whether indirect methods (utilizing historical laboratory data) could replace the direct approach (utilizing healthy reference individuals) and compared results with manufacturer-provided RIs for TSH and FT4.

MATERIAL AND METHODS

We collected historical data (2008—2022) from 13 Dutch laboratories to re-establish RIs by employing indirect methods, TMC (for TSH) and refineR (for FT4). Laboratories used common automated platforms (Roche, Abbott, Beckman or Siemens). Indirect RIs (IRIs) were determined per laboratory per year and clustered per manufacturer (>1.000.000 data points per manufacturer). Direct RIs (DRIs) were established in 125 healthy individuals per platform.

RESULTS

TSH IRIs remained robust over the years for all manufacturers. FT4 IRIs proved robust for three manufacturers (Roche, Beckman and Siemens), but the IRI upper reference limit (URL) of Abbott showed a decrease of 2 pmol/L from 2015. Comparison of the IRIs and DRIs for TSH and FT4 showed close agreement using adequate age-stratification. Manufacturer-provided RIs, notably Abbott, Roche and Beckman exhibited inappropriate URLs (overall difference of 0.5—1.0 µIU/mL) for TSH. For FT4, the URLs provided by Roche, Abbott and Siemens were overestimated by 1.5—3.5 pmol/L.

CONCLUSIONS

These results underscore the importance of RI verification as manufacturer-provided RIs are often incorrect and RIs may not be robust. Indirect methods offer cost-effective alternatives for laboratory-specific or platform-specific verification of RIs.

Keywords:

direct method
indirect method
reference intervals
thyroid disease

Authors:

Dirks N.F.

W.P.J. den Elzen

Hillebrand J.J.

Jansen H.I.

ten Boekel E.

Brinkman J.

Buijs M.M.

Demir A.Y.

Dijkstra I.M.

Endenburg S.C.

Engbers P.

Gootjes J.

M.J.W. Janssen

W.H.A. Kniest-de Jong

Kok M.B.

Kamphuis S.

Kruit A.

Michielsen E.

Wolthuis A.

Boelen A.

Heijboer A.C.

Received:

05.09.2024

Accepted:

11.10.2024

List of references:

  1. CLSI. Defining, establishing, and verifying reference intervals in the clinical laboratory; Approved guideline — Third Edition. CLSI document EP28-A3c. Wayne PA: Clinical and Laboratory Standards Institute; 2008.
  2. Ozcurumez MK, Haeckel R. Biological variables influencing the estimation of reference limits. Scand J Clin Lab Invest. 2018; 78(5):337-345.  https://doi.org/10.1080/00365513.2018.1471617
  3. Tate JR, Yen T, Jones GR. Transference and validation of reference intervals. Clin Chem. 2015;61:1012-1015. https://doi.org/10.1373/clinchem.2015.243055
  4. Haeckel R, Wosniok W. The importance of correct stratifications when comparing directly and indirectly estimated reference intervals. Clin Chem Lab Med. 2021;59:1628-33.  https://doi.org/10.1515/cclm-2021-0353
  5. Clinical and Laboratory Standards Institute (CLSI). Measurement procedure comparison and bias estimation using patient samples; approved guideline — third edition. CLSI document EP09-A3. Wayne PA: CLSI; 2013.
  6. Haeckel R, Wosniok W, Streichert T, 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. J Lab Med. 2021;45:35-53.  https://doi.org/10.1515/labmed-2020-0131
  7. Ammer T, Schützenmeister A, Prokosch HU, Zierk J, Rank CM, Rauh M. RIbench: A Proposed Benchmark for the Standardized Evaluation of Indirect Methods for Reference Interval Estimation. Clin Chem. 2022 Nov 03;68(11):1410-1424. https://doi.org/10.1093/clinchem/hvac142
  8. Wosniok W, Haeckel R. A new indirect estimation of reference intervals: truncated minimum chi-square (TMC) approach. Clin Chem Lab Med. 2019;57:1933-1947. https://doi.org/10.1515/cclm-2018-1341
  9. 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 Aug 06;11(1):16023. https://doi.org/10.1038/s41598-021-95301-2
  10. Haeckel R, Wosniok W, Arzideh F. Equivalence limits of reference intervals for partitioning of population data. Relevant differences of reference limits. Laboratoriums Medizin. 2016;40(3):199-205.  https://doi.org/10.1515/labmed-2016-0002
  11. Ozarda Y, Ichihara K, Jones G, Streichert T, Ahmadian R, IFCC, C-RIDL. Comparison of reference intervals derived by direct and indirect methods based on compatible datasets obtained in Turkey. Clin Chim Acta. 2021;520:186-195.  https://doi.org/10.1016/j.cca.2021.05.030
  12. Algeciras-Schimnich A, Bruns DE, Boyd JC, Bryant SC, La Fortune KA, Grebe SKG. Failure of current laboratory protocols to detect lot-to-lot reagent differences: findings and possible solutions. Clin Chem. 2013;59:1187-1194. https://doi.org/10.1373/clinchem.2013.205070
  13. Katzman BM, Ness KM, Algeciras-Schimnich A. Evaluation of the CLSI EP26-A protocol for detection of reagent lot-to-lot differences. Clin Biochem. 2017;50:768-771.  https://doi.org/10.1016/j.clinbiochem.2017.03.012
  14. Ma C, Cheng X, Xue F, Li, X, Yin Y, Wu, J, et al. Validation of an approach using only patient big data from clinical laboratories to establish reference intervals for thyroid hormones based on data mining. Clin Biochem. 2020;80:25-30.  https://doi.org/10.1016/j.clinbiochem.2020.03.012
  15. Arzideh F, Özcürümez M, Albers E, Haeckel R, Strecihert T. Indirect estimation of reference intervals using first or last results and results from patients without repeated measurements. J Lab Med. 2021;45:103-109.  https://doi.org/10.1515/labmed-2020-0149
  16. Thienpont LM, Van Uytfanghe K, Van Houcke S, Das B, Faix JD, MacKenzie F, et al. A progress report of the IFCC committee for standardization of thyroid function tests. Eur Thyroid J. 2014;3:109-116.  https://doi.org/10.1159/000358270
  17. Thienpont LM, Van Uytfanghe Beastall G, Faix JD, Ieiri T, Miller WG, et al. Report of the IFCC working group for standardization of thyroid function tests; part 1: thyroid-stimulating hormone. Clin Chem. 2010;56:902-911.  https://doi.org/10.1373/clinchem.2009.140178
  18. Thienpont LM, Van Uytfanghe Beastall G, Faix JD, Ieiri T, Miller WG, et al. Report of the IFCC working group for standardization of thyroid function tests; part 2: free thyroxine and free triiodothyronine. Clin Chem. 2010;56:912-920.  https://doi.org/10.1373/clinchem.2009.140194
  19. Thienpont LM, Faix JD, Beastall G. Standardization of free thyroxine and harmonization of thyrotropin measurements: a request for input from endocrinologists and other physicians. Thyroid. 2015;25:1379-1380. https://doi.org/10.1089/thy.2015.0309
  20. Raverot V, Bonjour M, du Payrat AJ, Perrin P, Roucher-Boulez F, Lasolle H, et al. Age- and sex-specific TSH upper-limit reference intervals in the general French population: there is a need to adjust our actual practices. J Clin Med. 2020;9(3):792.  https://doi.org/10.1530/endoabs.70.aep898
  21. Coene KL, Demir AY, Broeren MAC, Verschuure P, Lentjes EGWM, Boer AK. Subclinical hypothyroidism: a “laboratory-induced” condition? Eur J Endocrinol. 2015;173:499-505.  https://doi.org/10.1530/eje-15-0684
  22. Osinga JAJ, Derakhshan A, Palomaki GE, Ashoor G, Männistö T, Maraka S, et al. TSH and FT4 reference intervals in pregnancy: a systematic review and individual participant data meta-analysis. J Clin Endocrinol Metab 2022;107:2925-2933. https://doi.org/10.1210/clinem/dgac425
  23. Jansen HI, Bult MM, Bisschop PH, Boelen A, Heijboer AC, Hillebrand JJ. Increased fT4 concentrations in patients using levothyroxine without complete suppression of TSH. Endocr Connect. 2023;12:e220538. https://doi.org/10.1530/ec-22-0538

Close metadata

Contact the author
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

Contact us
If you have any questions, complaints or suggestions, please use this feedback form.
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.
Submit Application

You can become an author of one of our magazines, send a request and we will consider it in during the day.

Name
Phone
E-mail
Message
Login
Registration
E-mail
Password
Forgot Password?

Log in to the site using your account in one of the services

Password recovery
E-mail
Login
Register

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.