The role of a new polyclonal competitive thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer with structural disease but low levels of serum thyroglobulin by immunometric and LC-MS/MS methods

Abstract

Purpose

The aims of this study were to assess the role of an in-house competitive thyroglobulin assay (Tg-c) in the follow-up of metastatic differentiated thyroid carcinoma (DTC) patients who presented underestimated Tg measurements by immunometric assays (Tg-IMA) and to compare the results with IMA and LC-MS/MS Tg methods.

Methods

This prospective study included 40 patients. Twenty-one with metastatic disease: 14 had Tg-IMA levels inappropriately low or undetectable (eight patients with positive and six with borderline TgAb) and seven had high Tg-IMA levels. Nineteen had an excellent response to therapy. The competitive assay employs a polyclonal antibody produced in rabbits immunized with human Tg, Tg labeled with biotin, and for the solid phase separation, a monoclonal anti-rabbit IgG antibody adsorbed to microtiter plates.

Results

All 14 patients with structural disease and underestimated levels of Tg-IMA presented detectable Tg-c levels. The median Tg-c level in the group with positive TgAb was 183 µg/L (range: 22–710 µg/L), and 58 µg/L (range 23–148 µg/L) in the borderline TgAb group. The levels of Tg-LC-MS/MS were detectable in some patients (range < 0.5–18 µg/L). All seven patients with high Tg-IMA presented also high levels of Tg-c. Only 2/19 patients with excellent response had Tg-c levels above the functional sensitivity.

Conclusions

The competitive assay was able to detect Tg in all patients, even in the presence of serum TgAb, and may be an option in patients with underestimated Tg-IMA and relevant structural disease.

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Acknowledgements

The authors are very grateful to Dr. Maria Conceição Mamone for her expertise in thyroid cytopathology, to Dr. Elza Ikejiri for performing thyroid ultrasounds and to Angela Faria and Yeda Queiroga for their efficient laboratory administration. We are very grateful to the Head and Neck Surgical Team, particularly Drs. Flavio Hojaij, Marcel Palumbo, and Fabio Brodskyn.

Funding

This study was supported by Fleury, Medicina e Saúde.

Author contributions

All authors have given substantial contributions to the conception, acquisition, and analysis of the data of this work. All of them had also revised and approved the final version. L.G. and C.C.D.N. had special participation in the acquisition and analysis of the data. L.G., R.P.M.B., and R.M.B.M. were the main responsible for drafting this paper. J.G.H.V. and T.S.K. were the manly developers of the competitive assay. C.P.C. was the responsible for the statistic analysis. R.M.B.M., J.G.H.V., and R.P.M.B. had fundamental participation in the conception and design of this work. R.P.M.B. also coordinated all steps. All authors read and approved the final paper.

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Correspondence to Rosa Paula M. Biscolla.

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Conflict of interest

R.P.M.B., J.G.H.V., and R.M.B.M. are investigators of the Fleury Group.

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All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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All subjects signed the written informed consent and the institute’s committee on human research approved the study protocol.

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Guastapaglia, L., Kasamatsu, T.S., Nakabashi, C.C.D. et al. The role of a new polyclonal competitive thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer with structural disease but low levels of serum thyroglobulin by immunometric and LC-MS/MS methods. Endocrine (2020). https://doi.org/10.1007/s12020-020-02526-8

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Keywords

  • Thyroglobulin
  • LC-MS/MS
  • Competitive assay
  • Thyroglobulin antibodies and thyroid cancer