TSH and FT4 reference interval recommendations and prevalence of gestational thyroid dysfunction: quantification of current diagnostic approaches
Open accessAbstract
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.
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Recent meta-analyses have identified clinically relevant TSH and FT4 concentrations in pregnancy, and the need for assay and trimester-specific reference ranges.
“Recent meta-analyses have identified clinically relevant TSH and FT4 concentrations in pregnancy, 22 and the need for assay and trimester-specific reference ranges.23”
From Hypothyroidism (2024) · cites this paper as [23]
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References 34 · Cited by 27
- Authors
- Osinga, J. A. J., Derakhshan, A., Feldt-Rasmussen, U., Huang, K., Vrijkotte, T. G. M., Männistö, T., Bassols, J., López-Bermejo, A., Aminorroaya, A., Vafeiadi, M., Broeren, M. A. C., Palomaki, G. E., Ashoor, G., Chen, L., Lu, X., Taylor, P. N., Tao, F.-B., Brown, S. J., Sitoris, G., Chatzi, L., Vaidya, B., Popova, P. V., Vasukova, E. A., Kianpour, M., Suvanto, E., Grineva, E. N., Hattersley, A., Pop, V. J. M., Nelson, S. M., Walsh, J. P., Nicolaides, K. H., D’Alton, M. E., Poppe, K. G., Chaker, L., Bliddal, S., & Korevaar, T. I. M.
- Affiliations
- Erasmus MC (NL)
- Department of Medical Endocrinology and Metabolism, Copenhagen University Hospital, Rigshospitalet , 2100 Copenhagen , Denmark
- Anhui Medical University (CN)
- Amsterdam Public Health (NL)
- Oulu University Hospital (FI)
- Institut d'Investigació Biomèdica de Girona (ES)
- Pediatric Endocrinology Research Group, Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta Hospital , 17007 Girona , Spain
- Isfahan University of Medical Sciences (IR)
- University of Crete (GR)
- Máxima Medisch Centrum (NL)
- Brown University (US)
- Harris Birthright Research Centre for Fetal Medicine (GB)
- Ruian People's Hospital (CN)
- Cardiff University (GB)
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University , 230032 Anhui , China
- Sir Charles Gairdner Hospital (AU)
- Université Libre de Bruxelles (BE)
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California , Los Angeles, CA 90089 , USA
- University of Exeter (GB)
- Federal Almazov North-West Medical Research Centre (RU)
- University of Oulu (FI)
- Tilburg University (NL)
- University of Glasgow (GB)
- The University of Western Australia (AU)
- King's College London (GB)
- Columbia University Irving Medical Center (US)
- University of Copenhagen (DK)
- Corresponding author
- Osinga, Joris A J
- ORCID
- 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
- Palomaki, Glenn E
- Chen, Liangmiao
- Lu, Xuemian
- Taylor, Peter N
- Brown, Suzanne J
- Vaidya, Bijay
- Popova, Polina V
- Vasukova, Elena A
- Kianpour, Maryam
- 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
- Korevaar, Tim I M
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2023-09-22
- Volume
- 109
- Issue
- 3
- Pages
- 868-878
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC10876390
- OpenAlex
- W4386976773
- Cited by
- 27
- References
- 34
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 9
- FWCI
- 5.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, cc-by)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
- UWA Profiles and Research Repository (UWA) (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion)
- Funders
- Netherlands Organization for Scientific Research (401.16.020)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- thyroid-stimulating hormone, free thyroxine, reference values, levothyroxine therapy, overt hypothyroidism, subclinical hypothyroidism, subclinical hyperthyroidism, isolated hypothyroxinemia, diagnostic sensitivity, false discovery rate, overdiagnosis, underdiagnosis, pregnancy
- MeSH terms
- Female, Humans, Hypothyroidism, Pregnancy, Reference Values, Thyroid Function Tests, Thyrotropin, Thyroxine, Prevalence
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