Abstract

Overt hyperthyroidism (HT) during pregnancy is associated with a risk of maternal–fetal complications. Antithyroid drugs (ATD) have a potential risk for teratogenic effects and fetal–neonatal hypothyroidism. This study evaluated ATD treatment and thyroid function control during pregnancy, and pregnancy outcome in women with HT. Patients and methods: A retrospective analysis of 36 single fetus pregnancies in 29 consecutive women (median age 30.3 ± 4.7 years) with HT diagnosed before or during pregnancy; a control group of 39 healthy euthyroid pregnant women was used. Results: Twenty-six women had Graves’ disease (GD, 33 pregnancies), 1 had a hyperfunctioning autonomous nodule, and 2 had gestational transient thyrotoxicosis (GTT). Methimazole (MMI) was administered in 22 pregnancies (78.5%), Propylthiouracil (PTU) in 2 (7.1%), switch from MMI to PTU in 4 (14.2%), no treatment in 8 pregnancies (3 with subclinical HT, 5 euthyroid with previous GD remission before conception). In the 8 pregnancies of GD patients diagnosed during gestation or shortly before (<6 weeks), i.e., with fetal exposure to uncontrolled HT, there was 1 spontaneous abortion at 5 weeks (3.4% of all ATD-treated pregnancies), and 1 premature delivery at 32 weeks with neonatal death in 24 h (3.4%); 1 child had neonatal hyperthyroidism (3.3% of live children in GD women) and a small atrial sept defect (4% of live children in ATD treated women). In women treated more than 6 months until conception (20 pregnancies): (a) median ATD doses were lower than those in women diagnosed shortly before or during pregnancy; (b) ATD was withdrawn in 40% of pregnancies in trimester (T)1, all on MMI < 10 mg/day (relapse in 14.2%), and in up to 55% in T3; (c) TSH level was below normal in 37%, 35% and 22% of pregnancies in T1, T2 and T3 respectively; FT4 was increased in 5.8% (T1) and subnormal in 11.75% in T2 and T3; (d) no fetal birth defects were recorded; one fetal death due to a true umbilical cord knot was registered. Mean birth weight was similar in both ATD-treated and control groups. Hyperthyroidism relapsed postpartum in 83% of GD patients (at median 3 ± 2.6 months). Conclusion: In hyperthyroid women with long-term ATD treatment before conception, drugs could be withdrawn in T1 in 40% of them, the thyroid function control was better, and pregnancy and fetal complications were rarer, compared to women diagnosed during pregnancy. Frequent serum TSH and FT4 monitoring is needed to maintain optimal thyroid function during pregnancy.

Highlights

  • Hyperthyroidism occurs due to an inappropriately high synthesis and secretion of thyroid hormones by the thyroid gland and is characterized by a low/suppressed serum level of thyroid-stimulating hormone (TSH), associated with an increased level of peripheral hormones in the biochemically overt form of the disease, or with normal FT4 and FT3 levels in subclinical hyperthyroidism [1].In women, hyperthyroidism is related to menstrual cycle disorders and infertility [2]

  • Our study evaluated the rate of thyroid function control on antithyroid drugs (ATD) treatment during gestation and the pregnancy outcome in women with hyperthyroidism compared to a control group of healthy women

  • In this small retrospective study, we demonstrated that most women with hyperthyroidism treated with antithyroid drugs (ATD, usually methimazole)—had normal pregnancies

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Summary

Introduction

Hyperthyroidism occurs due to an inappropriately high synthesis and secretion of thyroid hormones by the thyroid gland and is characterized by a low/suppressed serum level of thyroid-stimulating hormone (TSH), associated with an increased level of peripheral hormones (total and free thyroxine-FT4 and/or total and free triiodothyronine-FT3) in the biochemically overt form of the disease, or with normal FT4 and FT3 levels in subclinical hyperthyroidism [1].In women, hyperthyroidism is related to menstrual cycle disorders (oligomenorrhea, amenorrhea) and infertility [2]. When the diagnosis of hyperthyroidism is made during the first trimester of pregnancy, the HCG-mediated hyperthyroidism, named gestational transient thyrotoxicosis (GTT), must be taken into account (prevalence 1–11% of pregnancies) [4,5]. In most cases, this is a subclinical hyperthyroidism, which appears after the 6th week of pregnancy due to the physiological rise in HCG secretion; HCG shares structural homology with TSH and stimulates maternal thyroid function, resulting in decreased TSH levels [6]. Other causes of thyrotoxicosis (toxic nodular goiters, thyroiditis) are less frequent during pregnancy

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