Prevalence of Thyrotoxicosis, Antithyroid Medication Use, and Complications Among Pregnant Women in the United States
Open accessAbstract
Background: Population-based estimates of the prevalence of thyrotoxicosis (TTX), the frequency of antithyroid drug (ATD) use, and risk of adverse events in pregnant women and their infants are lacking. Therefore, our objective was to obtain epidemiologic estimates of these parameters within a large population-based sample of pregnant women with TTX. Methods: A retrospective claims analysis was performed from the MarketScan Commercial Claims and Encounters health insurance database for the period 2005–2009. Women aged 15–44 years, enrolled for at least 2 years, and who had a pregnancy during the study period were included. Diagnosis of TTX was based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes using narrow (TTX-1=ICD 242.0) and broad (TTX-2=ICD 242.0 or 242.9) definitions. ATD use was based on prescriptions filled for propylthiouracil (PTU) or methimazole (MMI). Adverse events in mothers and infants were determined from the ICD-9-CM diagnosis codes recorded on submitted claims. Results: The database contained 904,497 eligible women. The average yearly prevalence per 1000 pregnant women was 2.46 for TTX-1 and 5.88 for TTX-2. Thirty-nine percent used ATD at any time during the study period. Compared to women without a TTX diagnosis, there was more than a twofold increase for liver disease among women with TTX (odds ratio [OR]=2.08, p <0.001) and a 13% increased risk for congenital anomalies (OR=1.13, p =0.014), but no association was observed with ATD use. The rates of congenital defects (per 1000 infants) associated with ATD use were 55.6 for MMI, 72.1 for PTU, and 65.8 for untreated women with TTX, compared to 58.8 among women without TTX. Conclusions: There was some indication of an elevated risk of liver disease and congenital anomalies in women with TTX, but the risk did not appear to be related to the ATD use. There seems to be a higher pregnancy termination rate for women with TTX on MMI, which likely reflects elective pregnancy terminations.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The absolute risk of PTU-associated liver failure observed in studies of U.S. health databases was low.
“However, even if this risk is real, the absolute risk observed in studies of U.S. health databases was low (433,465).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [465]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
DeGroot, L. J., Abalovich, M., Alexander, E. K., Amino, N., Barbour, L. A., Cobin, R. H., Eastman, C. J., Lazarus, J. H., Luton, D., Mandel, S. J., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2803 · Cited by 1,862 · see citing works
Abalovich, M., Amino, N., Barbour, L. A., Cobin, R. H., DeGroot, L. J., Glinoer, D., Mandel, S. J., & Stagnaro‐Green, A. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0141 · Cited by 929 · see citing works
Weetman, A. P. (2000) · New England Journal of Medicine · doi:10.1056/nejm200010263431707 · Cited by 821 · see citing works
Franklyn, J. A., & Boelaert, K. (2012) · The Lancet · doi:10.1016/s0140-6736(11)60782-4 · Cited by 262 · see citing works
Bahn, R. S., Burch, H. S., Cooper, D. S., Garber, J. R., Greenlee, C. M., Klein, I. L., Laurberg, P., McDougall, I. R., Rivkees, S. A., Ross, D., et al. (2009) · Thyroid · doi:10.1089/thy.2009.0169 · Cited by 223 · see citing works
Self-citationA comparison of propylthiouracil versus methimazole in the treatment of hyperthyroidism in pregnancy
Wing, D. A., Millar, L. K., Koonings, P. P., Montoro, M. N., & Mestman, J. H. (1994) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(94)70390-6 · Cited by 218 · see citing works
Steindel, S. J. (2010) · Journal of the American Medical Informatics Association · doi:10.1136/jamia.2009.001230 · Cited by 197 · see citing works
Mestman, J. H. (2004) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2004.03.005 · Cited by 176 · see citing works
Review of Antithyroid Drug Use During Pregnancy and Report of a Case of Aplasia Cutis
Mandel, S. J., Brent, G. A., & Larsen, P. R. (1994) · Thyroid · doi:10.1089/thy.1994.4.129 · Cited by 148 · see citing works
Propylthiouracil (PTU) Hepatoxicity in Children and Recommendations for Discontinuation of Use
Rivkees, S. A., & Mattison, D. R. (2009) · International Journal of Pediatric Endocrinology · doi:10.1155/2009/132041 · Cited by 135 · see citing works
Self-citationMethimazole, Carbimazole, and Congenital Skin Defects
van Dijke, C. P., HEYDENDAEL, R. J., & KLEINE, M. J. D. (1987) · Annals of Internal Medicine · doi:10.7326/0003-4819-106-1-60 · Cited by 133 · see citing works
Hornbrook, M. C., Whitlock, E. P., Berg, C. J., Callaghan, W. M., Bachman, D. J., Gold, R. B., Bruce, F. C., Dietz, P. M., & Williams, S. B. (2006) · Health Services Research · doi:10.1111/j.1475-6773.2006.00635.x · Cited by 131 · see citing works
Barbero, P., Valdéz, R., Rodriguez, H. A., Tiscornia, C., Mansilla, E., Allons, A., Coll, S., & Liascovich, R. (2008) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32497 · Cited by 128 · see citing works
Therapy Insight: management of Graves' disease during pregnancy
Chan, G. W., & Mandel, S. J. (2007) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0508 · Cited by 122 · see citing works
Emiliano, A. B., Governale, L. A., Parks, M. A., & Cooper, D. S. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2752 · Cited by 110 · see citing works
Propylthiouracil (PTU) Hepatoxicity in Children and Recommendations for Discontinuation of Use
Rivkees, S., & Mattison, D. (2009) · International Journal of Pediatric Endocrinology · doi:10.1186/1687-9856-2009-132041 · Cited by 90 · see citing works
Self-citationPropylthiouracil Versus Methimazole in Treatment of Graves' Disease During Pregnancy
Chattaway, J. M., & Klepser, T. B. (2007) · Annals of Pharmacotherapy · doi:10.1345/aph.1h535 · Cited by 52 · see citing works
Aplasia cutis congenita and methimazole.
Bachrach, L. K., & Burrow, G. N. (1984) · PubMed · Cited by 33 · see citing works
Methimazole embryopathy: A contribution to defining the phenotype
Valdéz, R., Barbero, P., Liascovich, R., Rosa, L. F. D., Aguirre, M., & Alba, L. G. (2006) · Reproductive Toxicology · doi:10.1016/j.reprotox.2006.11.007 · Cited by 30 · see citing works
Rivkees, S. A., & Mandel, S. J. (2011) · Hormone Research in Paediatrics · doi:10.1159/000329186 · Cited by 24 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [20]American Medical Association Current Procedural Terminology procedure codes. www.ama-assn.org/ama/pub/physician-resources/solutions-managing-your-practice/coding-billing-insurance/cpt.page. [Apr 20;2013 ]. www.ama-assn.org/ama/pub/physician-resources/solutions-managing-your-practice/coding-billing-insurance/cpt.page
Cited by
Sorted by citations
Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., Rivkees, S. A., Samuels, M., Sosa, J. A., Stan, M. N., et al. (2016) · Thyroid® · doi:10.1089/thy.2016.0229 · Cited by 2,938 · see citing works
“study, 31% of women who had received MMI around the time of conception had elective termination of pregnancy versus 9% of those who received PTU, and it was hypothesized that fear of MMI-associated birth defects had led to the decision to terminate pregnancy (465).”
BackgroundSelf-citationGlobal epidemiology of hyperthyroidism and hypothyroidism
Taylor, P. N., Albrecht, D., Scholz, A., Gutierrez-Buey, G., Lazarus, J. H., Dayan, C. M., & Okosieme, O. E. (2018) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2018.18 · Cited by 1,552 · see citing works
De Leo, S., Lee, S. Y., & Braverman, L. E. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00278-6 · Cited by 883 · see citing works
Cooper, D. S., & Laurberg, P. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70086-x · Cited by 310 · see citing works
Birth Defects After Early Pregnancy Use of Antithyroid Drugs: A Danish Nationwide Study
Andersen, S. L., Olsen, J., Wu, C. S., & Laurberg, P. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2831 · Cited by 267 · see citing works
Laurberg, P., & Andersen, S. L. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0135 · Cited by 115 · see citing works
Ailes, E. C., Simeone, R. M., Dawson, A. L., Petersen, E. E., & Gilboa, S. M. (2016) · Birth Defects Research Part A: Clinical and Molecular Teratology · doi:10.1002/bdra.23573 · Cited by 112 · see citing works
Lo, J. C., Rivkees, S. A., Chandra, M., Gonzalez, J. R., Korelitz, J. J., & Kuzniewicz, M. W. (2015) · Thyroid® · doi:10.1089/thy.2014.0434 · Cited by 51 · see citing works
Self-citation
- Authors
- Korelitz, J. J., McNally, D. L., Masters, M. N., Li, S. X., Xu, Y., & Rivkees, S. A.
- Affiliations
- Westat (United States) (US)
- University of Maryland, Baltimore (US)
- University of Florida (US)
- Corresponding author
- Korelitz, James J.
- ORCID
- Rivkees, Scott A.
- Venue
- Thyroid®
- Publisher
- SAGE Publications
- Published
- 2013-06
- Volume
- 23
- Issue
- 6
- Pages
- 758-765
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- PMC
- PMC3675839
- OpenAlex
- W2008865736
- Cited by
- 91
- References
- 20
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 7 · 2021: 5 · 2020: 6 · 2019: 7 · 2018: 8 · 2017: 6 · 2016: 17 · 2015: 11 · 2014: 8 · 2013: 3
- FWCI
- 5.65
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Thyroid (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD065200, R01HD65200)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- thyrotoxicosis, antithyroid drugs, pregnancy, propylthiouracil, methimazole, congenital malformations, liver disease, abortion, maternal adverse events, prevalence, drug safety in pregnancy, MarketScan claims data, ICD-9-CM codes
- MeSH terms
- Congenital Abnormalities, Abnormalities, Drug-Induced, Adolescent, Adult, Female, Humans, Infant, Infant, Newborn, Insurance, Health, Methimazole, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, Drug Prescriptions, Propylthiouracil, Retrospective Studies, Antithyroid Agents, Thyrotoxicosis, United States, Prevalence, International Classification of Diseases, Hepatic Insufficiency, Young Adult, Chemical and Drug Induced Liver Injury
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
