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TSH and FT4 reference interval recommendations and prevalence of gestational thyroid dysfunction: quantification of current diagnostic approaches

Osinga, Joris A. J., Derakhshan, Arash, Feldt-Rasmussen, Ulla, Huang, Kun, Vrijkotte, Tanja G. M., Männistö, Tuija, Bassols, Judit, López-Bermejo, Abel, Aminorroaya, Ashraf, Vafeiadi, Marina, Broeren, Maarten A. C., Palomaki, Glenn E., Ashoor, Ghalia, Chen, Liangmiao, Lu, Xuemian, Taylor, Peter N. ORCID:, Tao, Fang-Biao, Brown, Suzanne J., Sitoris, Georgiana, Chatzi, Lida, Vaidya, Bijay, Popova, Polina V., Vasukova, Elena A., Kianpour, Maryam, Suvanto, Eila, Grineva, Elena N., Hattersley, Andrew, Pop, Victor J. M., Nelson, Scott M., Walsh, John P., Nicolaides, Kypros H., D'Alton, Mary E., Poppe, Kris G., Chaker, Layal, Bliddal, Sofie and Korevaar, Tim I. M. 2024. TSH and FT4 reference interval recommendations and prevalence of gestational thyroid dysfunction: quantification of current diagnostic approaches. The Journal of Clinical Endocrinology & Metabolism 109 (3) , pp. 868-878. 10.1210/clinem/dgad564

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Context Guidelines recommend use of population- and trimester-specific TSH and FT4 reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. Methods We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using non-pregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. Results The study population comprised 52,496 participants from 18 cohorts. Compared to the use of trimester-specific reference intervals, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction and non-pregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. Conclusion Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable over- and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Oxford University Press
ISSN: 0021-972X
Date of First Compliant Deposit: 5 October 2023
Date of Acceptance: 21 September 2023
Last Modified: 06 Mar 2024 15:03

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