Substituting Potassium Iodide for Methimazole as the Treatment for Graves' Disease During the First Trimester May Reduce the Incidence of Congenital Anomalies: A Retrospective Study at a Single Medical Institution in Japan
Abstract
BACKGROUND: To control hyperthyroidism due to Graves' disease, antithyroid drugs should be administered. Several studies have shown that exposure to methimazole (MMI) during the first trimester of pregnancy increases the incidence of specific congenital anomalies that are collectively referred to as MMI embryopathy. Congenital anomalies associated with exposure to propylthiouracil (PTU) have also recently been reported. METHODS: This study investigated whether substituting potassium iodide (KI) for MMI in the first trimester would result in a lower incidence of major congenital anomalies than continuing treatment with MMI alone. The cases of 283 women with Graves' disease (GD) were reviewed whose treatment was switched from MMI to KI in the first trimester (iodine group), as well as the cases of 1333 patients treated with MMI alone (MMI group) for comparison. Another major outcome of interest was the incidence of neonatal thyroid dysfunction. The subjects of the analysis of major congenital anomalies and neonatal thyroid dysfunction were live-born infants. RESULTS: The incidence of major anomalies was 4/260 (1.53%) in the iodine group, which was significantly lower than the incidence of 47/1134 (4.14%) in the MMI group. Two neonates in the iodine group had anomalies consistent with MMI embryopathy (0.8%), as opposed to 18 neonates in the MMI group (1.6%). None of the neonates exposed to KI had thyroid dysfunction or goiter. CONCLUSIONS: Substituting KI for MMI as a means of controlling hyperthyroidism in GD patients during the first trimester may reduce the incidence of congenital anomalies, at least in iodine-sufficient regions.
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Live births were more common in the group that shifted to iodine than in the group that continued MMI therapy (91.9% vs. 85.1%, p < 0.05).
“Despite this, live births were more common in the group that had shifted than in the group that had continued MMI therapy (91.9% vs. 85.1%, p < 0.05).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [476]
The prevalence of major birth defects was lower in women who shifted to iodine therapy than in women who continued MMI therapy (1.53% vs. 4.14%, p < 0.05).
“The prevalence of major birth defects was lower in the women who had shifted to iodine therapy (1.53% vs. 4.14%, p < 0.05).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [476]
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References 29 · Cited by 56
- Authors
- Yoshihara, A., Noh, J. Y., Watanabe, N., Mukasa, K., Ohye, H., Suzuki, M., Matsumoto, M., Kunii, Y., Suzuki, N., Kameda, T., Iwaku, K., Kobayashi, S., Sugino, K., & Ito, K.
- Affiliations
- Ito Hospital (JP)
- ORCID
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2015-10
- Volume
- 25
- Issue
- 10
- Pages
- 1155-1161
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W1899098051
- Cited by
- 56
- References
- 29
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 8 · 2020: 8 · 2019: 6 · 2018: 3 · 2017: 9 · 2016: 4
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (15K09296)
- 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 › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- Graves' disease, potassium iodide, methimazole, propylthiouracil, first trimester, congenital malformations, neonatal thyroid dysfunction, hyperthyroidism in pregnancy
- MeSH terms
- Abnormalities, Drug-Induced, Adult, Female, Graves Disease, Humans, Japan, Methimazole, Potassium Iodide, Pregnancy, Pregnancy Complications, Pregnancy Trimester, First, Retrospective Studies, Antithyroid Agents, Thyrotropin, Thyroxine, Triiodothyronine, Incidence, Treatment Outcome, Drug Substitution
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