Stimulating thyrotropin receptor antibodies in early pregnancy

Nanna Maria Uldall-Torp; Lærke Andersen; Hannah Jaekyung Kim; Niels Henrik Bruun; Jesper Karmisholt; Stig Andersen; Stine Linding Andersen

doi:10.1515/cclm-2024-0258

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Article

Stimulating thyrotropin receptor antibodies in early pregnancy

Nanna Maria Uldall-Torp , Lærke Andersen , Hannah Jaekyung Kim , Niels Henrik Bruun , Jesper Karmisholt , Stig Andersen and Stine Linding Andersen

Published/Copyright: April 19, 2024

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 11

Abstract

Objectives

Thyrotropin-receptor antibodies (TRAb) are used to diagnose Graves’ hyperthyroidism in pregnant women. Bioassays provide a measure of thyrotropin-receptor stimulatory antibodies (TSI) specifically. The objective was to measure TSI in pregnant women for establishment of a pregnancy-specific cut-off and comparison with immunoassay measurements of TRAb.

Methods

The retrospective Danish study was performed within the North Denmark Region Pregnancy Cohort (2011–2015) that includes stored biobank samples from early pregnancy (median week 10) with immunoassay measurements of thyroid function parameters and TRAb. TSI were measured in the same samples using the Turbo TSI bioassay (Quidel/Ortho-Clinical Diagnostics) with a recommended cut-off of 0.0241 IU/L in non-pregnant adults. A pregnancy-specific TSI cut-off (95-percentile) was established using Regression on Order Statistics.

Results

The established TSI cut-off was 0.0418 IU/L (95 % CI: 0.0417–0.0419). Among women with early pregnancy hyperthyroidism (n=438), 43 women (9.8 %) were TSI positive using the established cut-off, and these women had lower TSH (median 0.008 mIU/L) compared to women with TSI levels below 0.0241 (median TSH 0.040 mIU/L) or in the range from 0.0241 to 0.0418 (median TSH 0.033 mIU/L). Among the 438 women with early pregnancy hyperthyroidism, 22 women were positive for TSI and TRAb, 388 were negative for both, and 28 women were positive for either TSI or TRAb.

Conclusions

This is the first study on TSI measurements in a large cohort of early pregnant women. A pregnancy-specific cut-off for TSI was established and agreement in the classification with immunoassay measurements of TRAb was seen in 94 % of cases.

Keywords: Graves’ disease; hyperthyroidism; thyroid disease; thyrotropin-receptor antibodies (TRAb); thyrotropin-receptor stimulatory antibodies (TSI)

Corresponding author: Nanna Maria Uldall-Torp, MD, Department of Clinical Biochemistry, Aalborg University Hospital, Hobrovej 18-22, 9000 Aalborg, Denmark, E-mail: nanna.torp@rn.dk

Funding source: Quidel/Ortho-Clinical Diagnostics

Award Identifier / Grant number: supported the Turbo TSI bioassay measurements

Research ethics: The study was approved by the North Denmark Region Committee on Health Research Ethics (N-20150015) and registered according to the General Data Protection Regulation in the North Denmark Region (2015-34).
Informed consent: Not applicable.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission. NT and SLA conceptualized the study. NT performed data analyses and wrote the first draft of the manuscript. LA and HJK performed the TSI measurements. All authors contributed to the interpretation and approved the final manuscript.
Competing interests: The authors state no conflict of interest.
Research funding: Quidel/Ortho-Clinical Diagnostics supported the Turbo TSI bioassay measurements.
Data availability: Restrictions apply to the availability of data generated or analyzed during this study to preserve patient confidentiality or because they were used under license according to the GDPR regulations. The corresponding author will on request detail the restrictions and any conditions under which access to some data may be provided.

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Received: 2024-02-27

Accepted: 2024-04-08

Published Online: 2024-04-19

Published in Print: 2024-10-28

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Articles in the same Issue

https://doi.org/10.1515/cclm-2024-0258

Keywords for this article

Graves’ disease; hyperthyroidism; thyroid disease; thyrotropin-receptor antibodies (TRAb); thyrotropin-receptor stimulatory antibodies (TSI)