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

Joris A J Osinga*, Arash Derakhshan, Ulla Feldt-Rasmussen, Kun Huang, Tanja G M Vrijkotte, Tuija Männistö, Judit Bassols, Abel López-Bermejo, Ashraf Aminorroaya, Marina Vafeiadi, Maarten A C Broeren, Glenn E Palomaki, Ghalia Ashoor, Liangmiao Chen, Xuemian Lu, Peter N Taylor, Fang-Biao Tao, Suzanne J Brown, Georgiana Sitoris, Lida ChatziBijay Vaidya, Polina V Popova, Elena A Vasukova, Maryam Kianpour, Eila Suvanto, Elena N Grineva, Andrew Hattersley, Victor J M Pop, Scott M Nelson, John P Walsh, Kypros H Nicolaides, Mary E D'Alton, Kris G Poppe, Layal Chaker, Sofie Bliddal, Tim I M Korevaar

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
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Context: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (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 nonpregnancy 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 with the use of trimester-specific RIs, 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 nonpregnancy 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 overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

Original languageEnglish
Pages (from-to)868-878
Number of pages11
JournalThe Journal of clinical endocrinology and metabolism
Issue number3
Early online date22 Sept 2023
Publication statusPublished - 1 Mar 2024

Bibliographical note

Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society.


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