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Licensed Unlicensed Requires Authentication Published by De Gruyter February 25, 2022

Dubiously increased FT4 and FT3 levels in clinically euthyroid patients: clinical finding or analytical pitfall?

  • Martin Külz EMAIL logo , Stephan Fellner , Jörg Rocktäschel , Uta Ceglarek , Anja Willenberg and Jürgen Kratzsch

Abstract

Objectives

We systematically investigated normally or subclinically increased thyroid stimulating hormone (TSH) values associated with unexpectedly increased thyroxine (FT4) and free triiodothyronine (FT3) in findings of patients without any thyroid disease. Moreover, we looked for alternatives to overcome such states with an improved diagnostic procedure and to investigate the pathogenetic background of the respective patients.

Methods

Samples with TSH concentrations within the range of 0.4–10 mU/L combined with increased concentrations of FT4 (n=120; Cobas, Roche) were collected over a period of around six years. Cobas FT4 results were compared with measurements from Liaison (DiaSorin) and Architect (Abbott) FT4 assays. For further validation all samples were measured for total thyroxine (TT4) (Cobas, Roche). Finally, FT3 and TT3 as complementary parameters were measured in samples with leftover material. To overcome potential analytical disturbances from stimulating heterophilic antibodies, we used heterophilic blocking tubes (HBTs).

Results

From the 120 samples with increased FT4 concentrations by Cobas, 51/120 were also increased by Liaison, and 26/120 by Architect. However, the measurement of TT4 indicated only n=10/120 increased values. The number of increased FT3 (n=71) measurements was higher in Architect>Cobas>Liaison (28>27>9). TT3 levels of 70/71 samples were within the reference interval. HBTs were inappropriate to reduce unspecific immunoreactivity in our samples. No clear pathogenetic background could be elucidated in the anamnesis of individual patients.

Conclusions

To overcome dubious constellations of TSH, FT4, and FT3, it is helpful to measure TT4 and TT3 for control or to use an immunoassay with an alternative assay design for the respective parameters.


Corresponding author: Martin Külz, Institute for Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, (ILM) Leipzig University, Paul-List-Str. 13–15, 04103 Leipzig, Germany, Email:

Funding source: pes Medizinische Diagnosesysteme GmbH

Acknowledgments

The authors would like to thank all patients, technicians, and technical staff for contributing to this study.

  1. Research funding: This study was supported by a research grant from pes Medizinische Diagnosesysteme GmbH, Germany.

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

  3. Informed consent: Informed consent was obtained from all individuals included in this study.

  4. Ethical approval: Ethics approval (383/19 and 082-10-19042010) was available for this study.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2021-1211).


Received: 2021-11-18
Accepted: 2022-02-13
Published Online: 2022-02-25
Published in Print: 2022-05-25

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