Pregnancy outcome in women treated with methimazole or propylthiouracil during pregnancy

Gianetti, Elena; Russo, Laura; Orlandi, Fabio; Chiovato, Luca; Giusti, Massimo; Benvenga, Salvatore; Moleti, Mariacarla; Vermiglio, Francesco; Macchia, Paolo Emidio; Vitale, Mario; Regalbuto, Concetto; Centanni, Marco; Martino, Enio; Vitti, Paolo; Tonacchera, Massimo

doi:10.1007/s40618-015-0281-z

Cited by 44 publications

(48 citation statements)

References 42 publications

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“…129,130 Propylthiouracil is generally used during the first trimester of pregnancy and then switched to thiamazole in the second trimester, because of the associated risk of first trimester thiamazole-induced embryopathy. Although some authors argue that this association could be explained by hyperthyroidism, rather than by ATD administration, 131 birth defects including aplasia cutis, choanal atresia, oesophageal atresia, and omphalocele have been described with thiamazole administration and not in patients with hyperthyroidism per se. 132–134 Although less common, propylthiouracil has also been shown to be associated with birth defects in the face and neck, and urinary systems.…”

Section: Special Circumstancesmentioning

confidence: 99%

Hyperthyroidism

2016

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Hyperthyroidism is characterised by increased thyroid hormone synthesis and secretion from the thyroid gland, whereas thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source. The most common cause of hyperthyroidism is Graves’ disease, followed by toxic nodular goitre. Other important causes of thyrotoxicosis include thyroiditis, iodine-induced and drug-induced thyroid dysfunction, and factitious ingestion of excess thyroid hormones. Treatment options for Graves’ disease include antithyroid drugs, radioactive iodine therapy, and surgery, whereas antithyroid drugs are not generally used long term in toxic nodular goitre, because of the high relapse rate of thyrotoxicosis after discontinuation. β blockers are used in symptomatic thyrotoxicosis, and might be the only treatment needed for thyrotoxicosis not caused by excessive production and release of the thyroid hormones. Thyroid storm and hyperthyroidism in pregnancy and during the post-partum period are special circumstances that need careful assessment and treatment.

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Section: Special Circumstancesmentioning

confidence: 99%

Hyperthyroidism

2016

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“…Overall, the defects were less severe than the MMI/CMZassociated defects (60), and they consisted of face and neck malformations (preauricular sinus and cysts), and urinary tract malformations (confined to boys). Some uncertainty has existed in this area of research, because some investigators found no association between ATD use in pregnancy and birth defects (61,62,63,64). As recently reviewed in detail (65), the cause for the negative findings likely resides with the methods used in the studies.…”

Section: Therapy Of Graves' Disease and The Risk Of Birth Defectsmentioning

confidence: 99%

ENDOCRINOLOGY IN PREGNANCY: Pregnancy and the incidence, diagnosing and therapy of Graves’ disease

Laurberg

Andersen

2016

European Journal of Endocrinology

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Thyroid hormones are essential developmental factors, and Graves' disease (GD) may severely complicate a pregnancy. This review describes how pregnancy changes the risk of developing GD, how early pregnancy by several mechanisms leads to considerable changes in the results of the thyroid function tests used to diagnose hyperthyroidism, and how these changes may complicate the diagnosing of GD. Standard therapy of GD in pregnancy is anti-thyroid drugs. However, new studies have shown considerable risk of birth defects if these drugs are used in specific weeks of early pregnancy, and this should be taken into consideration when planning therapy and control of women who may in the future become pregnant. Early pregnancy is a period of major focus in GD, where pregnancy should be diagnosed as soon as possible, and where important and instant change in therapy may be warranted. Such change may be an immediate stop of anti-thyroid drug therapy in patients with a low risk of rapid relapse of hyperthyroidism, or it may be an immediate shift from methimazole/carbimazole (with risk of severe birth defects) to propylthiouracil (with less risk), or maybe to other types of therapy where no risk of birth defects have been observed. In the second half of pregnancy, an important concern is that not only the mother with GD but also her foetus should have normal thyroid function.Thyroid hormones are essential developmental factors as first shown by Gudernatsch when he, in 1912, fed tadpoles thyroid tissue and observed metamorphosis (1). In mammals, thyroid hormones are especially of importance for brain development (2, 3), and even a few months with lack of thyroid hormones in infant life may lead to irreversible brain damage. This is the background for the universal screening for congenital hypothyroidism performed in many countries. However, thyroid hormones are also important for normal pregnancy, and maternal thyroid disease may severely increase the risk of pregnancy complications, including Invited author's profile Peter Laurberg was Clinical Professor of Internal Medicine and Endocrinology, Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. His research mainly focused on thyroid disease prevention, epidemiology, diagnosing and therapy, including studies on iodine and thyroid, and pregnancy and thyroid. He had special research interest on the risk from and optimal management of autoimmune hypo-and hyperthyroidism in pregnancy and post-partum, management of Graves' disease in general, and how the burden of thyroid disease can be minimized by adjusting the population's iodine intake. He has coauthored several international guidelines on thyroid disease management, including management of thyrotoxicosis, and thyroid disease in pregnancy. Peter Laurberg died June 20, 2016.

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“…Li et al found that PTU was a safer choice for treating pregnant women with hyperthyroidism with respect to the risk of birth defects [9]. Moreover, several trials found no association between the use of ATDs in pregnancy and neonatal congenital malformations [10]. …”

Section: Introductionmentioning

confidence: 99%

Effects of methimazole and propylthiouracil exposure during pregnancy on the risk of neonatal congenital malformations: A meta-analysis

Song

Lin²,

Chen

et al. 2017

PLoS ONE

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ObjectiveThe aim of this study was to determine the effect of exposure to different antithyroid drugs during pregnancy on the incidence of neonatal congenital malformations.MethodsA meta-analysis was performed to compare the incidence of neonatal congenital malformations after exposure to different antithyroid drugs during pregnancy. Twelve studies that met the inclusion criteria were included in this meta-analysis. PubMed, Embase, and CENTRAL databases were searched from inception until January 2017. Study designs included case–control studies, prospective cohort studies, and retrospective cohort studies.ResultsTwelve studies involving 8028 participants with exposure to different antithyroid drugs during pregnancy were included in this study; however, only 10 studies involving 5059 participants involved exposure to different antithyroid drugs exactly during pregnancy. Our results indicated that exposure to methimazole (MMI)/carbimazole (CMZ) only during pregnancy significantly increased the risk of neonatal congenital malformations compared to no antithyroid drug exposure (OR 1.88; 95%CI 1.33 to 2.65; P = 0.0004). No differences were observed between propylthiouracil (PTU) exposure and no antithyroid drug exposure only during pregnancy (OR 0.81; 95%CI 0.58 to 1.15; P = 0.24). Exposure to MMI/CMZ only during pregnancy significantly increased the risk of neonatal congenital malformations compared to that associated with exposure to PTU (OR 1.90; 95%CI 1.30 to 2.78; P = 0.001).ConclusionFor pregnant women with hyperthyroidism, exposure to MMI/CMZ significantly increased the incidence of neonatal congenital malformations compared to exposure to PTU and no antithyroid drug exposure; however, no differences were observed between PTU exposure and no antithyroid drug exposure.

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Pregnancy outcome in women treated with methimazole or propylthiouracil during pregnancy

Cited by 44 publications

References 42 publications

Hyperthyroidism

Hyperthyroidism

ENDOCRINOLOGY IN PREGNANCY: Pregnancy and the incidence, diagnosing and therapy of Graves’ disease

Effects of methimazole and propylthiouracil exposure during pregnancy on the risk of neonatal congenital malformations: A meta-analysis

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