Dose-Dependent Influence of Antithyroid Drugs on the Difference in Free Thyroxine Levels between Mothers with Graves' Hyperthyroidism and Their Neonates

Hiroyuki Iwaki; Kenji Ohba; Eisaku Okada; Takeshi Murakoshi; Yumiko Kashiwabara; Chiga Hayashi; Akio Matsushita; Shigekazu Sasaki; Takafumi Suda; Yutaka Oki; Rieko Gemma

doi:10.1159/000509324

Dose-Dependent Influence of Antithyroid Drugs on the Difference in Free Thyroxine Levels between Mothers with Graves' Hyperthyroidism and Their Neonates

Eur Thyroid J. 2021 Jul;10(5):372-381. doi: 10.1159/000509324. Epub 2020 Aug 19.

Authors

Affiliations

¹ Division of Endocrinology, Department of Internal Medicine, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
² Medical Education Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
³ Department of Community Health and Preventive Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
⁴ Obstetrics and Gynecology, Maternal and Perinatal Care Center, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
⁵ Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
⁶ Department of Metabolism and Endocrinology, Hamamatsu-Kita Hospital, Hamamatsu, Japan.

Abstract

Background: Several guidelines have recommended that the use of the lowest effective dose of antithyroid drugs (ATDs) that maintains maternal serum free thyroxine (FT4) levels at or moderately above the upper limit of the reference range is appropriate for fetal euthyroid status. However, little is known about whether ATD dosage affects the difference in serum FT4 levels between the mother and neonate. We conducted a retrospective study at a tertiary hospital in Japan to investigate the dose-dependent influence of ATDs on both maternal and fetal thyroid hormone status.

Materials and methods: We retrospectively examined 62 pregnant women who delivered between 2007 and 2016 and were treated for Graves' hyperthyroidism with ATD at any stage during pregnancy. We selected individuals whose data on maternal FT4 level within 4 weeks of their deliveries and cord FT4 level of their infants at the time of delivery were available. Those with multiple pregnancies, iodine or glucocorticoid treatment, and fetal goiter detected by ultrasonography were excluded.

Results: After the exclusion criteria were applied, we recruited 40 individuals. The cord FT4 levels were significantly lower than the maternal FT4 levels in patients treated with high-dosage ATDs (methimazole >5 mg daily or propylthiouracil >100 mg daily). However, there were no significant differences between maternal and cord FT4 levels in patients treated with low-dosage ATDs (methimazole ≤5 mg daily or propylthiouracil ≤100 mg daily). We selected 35 individuals whose data on maternal thyrotropin receptor-binding inhibitory immunoglobulin (TBII) level were available. Multiple linear regression analysis adjusted for ATD dosage, maternal TBII level, and gestational period found that ATD dosage was a significant predictor of the difference in serum FT4 levels between the mother and neonate. In terms of maternal complications, multiple logistic regression analysis identified maternal free triiodothyronine (FT3) level as a significant predictor of the incidence of preterm delivery.

Conclusions: We found a dose-dependent influence of ATDs on the difference in serum FT4 levels between mothers with Graves' hyperthyroidism and their neonates. Further studies to evaluate the optimal target FT4 and FT3 levels for the mother and neonate during pregnancy may improve the outcome of pregnant women with Graves' hyperthyroidism.

Keywords: Antithyroid drugs; Graves' disease; Neonatal thyroid dysfunction; Pregnancy; Thyroxine.