Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Hyperthyroidism in Pregnancy: the Delicate Balance between too Much or too Little Antithyroid Drug

Version 1 : Received: 26 June 2021 / Approved: 30 June 2021 / Online: 30 June 2021 (00:09:17 CEST)

A peer-reviewed article of this Preprint also exists.

Gheorghiu, M.L.; Bors, R.G.; Gheorghisan-Galateanu, A.-A.; Pop, A.L.; Cretoiu, D.; Varlas, V.N. Hyperthyroidism in Pregnancy: The Delicate Balance between too Much or too Little Antithyroid Drug. J. Clin. Med. 2021, 10, 3742. Gheorghiu, M.L.; Bors, R.G.; Gheorghisan-Galateanu, A.-A.; Pop, A.L.; Cretoiu, D.; Varlas, V.N. Hyperthyroidism in Pregnancy: The Delicate Balance between too Much or too Little Antithyroid Drug. J. Clin. Med. 2021, 10, 3742.

Journal reference: J. Clin. Med. 2021, 10, 3742
DOI: 10.3390/jcm10163742

Abstract

Overt hyperthyroidism during pregnancy is associated with risk of maternal-fetal complications. The antithyroid drugs (ATD) have a potential risk for teratogenic effects and fetal–neonatal hy-pothyroidism. This study evaluated ATD treatment and thyroid function control during preg-nancy, and pregnancy outcome in women with hyperthyroidism. Patients and methods: retro-spective analysis of 36 single fetus pregnancies in 29 consecutive women (median age 30.3 ± 4.7 years) with hyperthyroidism diagnosed before or during pregnancy; a control group of 39 healthy euthyroid pregnant women was used. Results: 26 women had Graves’ disease (GD, 33 pregnan-cies), 1 had a hyperfunctioning autonomous nodule, 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 hyperthyroidism, 5 euthyroid with previous GD remission before conception). One spontaneous abortion at 5 weeks (3.4% of pregnancies) and 1 premature delivery at 32 weeks with perinatal death in 24h (3.4%) were recorded in 2 of the 8 pregnancies of GD patients diagnosed shortly before (< 6 weeks) or during gestation. 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a) median ATD doses were lower than those in women diagnosed shortly before or during pregnancy; b) ATD was withdrawn in 40% of pregnancies in trimester (T) I, all on MMI < 10 mg/day (relapse in 14.2%), and in up to 55% in TIII; c) TSH level was below normal in 37%, 35% and 22% of pregnancies in T I, II and III respectively; FT4 was increased in 5.8% (T I) and sub-normal in 11.75% in TII and III; d) one fetal death due to a true umbilical cord knot was recorded. Hyperthyroidism relapsed postpartum in 83% of GD patients (at median 3 ± 2.6 months). One 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). Mean birth weight did not differ from that of the control group. Conclusion. In hyperthyroid women with long-term ATD control before con-ception, drugs could be withdrawn in TI in a third of them, and fetal complications were rare. Frequent serum TSH and FT4 monitoring is needed in order to maintain optimal thyroid function during pregnancy.

Keywords

hyperthyroidism; thyrotoxicosis; Graves’ disease; pregnancy; antithyroid drug; drug withdrawal; postpartum recurrence; birth defects

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