Andersen Stine Linding, Andersen Stig
Department of Clinical Biochemistry, Aalborg University Hospital, Hobrovej 18-22, 9000 Aalborg, Denmark.
Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark.
Thyroid Res. 2020 Jun 27;13:11. doi: 10.1186/s13044-020-00085-8. eCollection 2020.
Antithyroid drugs (ATDs) are preferred for the treatment of hyperthyroidism caused by Graves' disease in pregnant women. The drugs have been a recognized treatment for decades, and a general risk of side effects is known. For the use of ATDs in pregnancy, a concern about teratogenic side effects has been brought forward since the 1970s. In more recent years, a number of large observational studies have added new evidence and quantified the risk of birth defects associated with different types of ATDs. The findings that both Methimazole (MMI) and Propylthiouracil (PTU) are associated with birth defects have challenged the clinical recommendations on the treatment of hyperthyroidism in pregnancy, and certain aspects remain unclarified. In this review, the current evidence on the risk of birth defects associated with the use of ATDs in early pregnancy is described, and determinants of causality are discussed. This includes the current evidence of a biological gradient and the role of maternal thyroid function per se Finally, clinical aspects of the timing and type of treatment is discussed, and future perspectives are addressed. Current evidence corroborates a risk of birth defects associated with MMI while more evidence is needed to determine the teratogenic potential of PTU. Detailed assessment of type and timing of exposure in large cohorts are needed. Moreover, studies investigating alternative or new treatments are warranted.
抗甲状腺药物（ATD）是治疗孕妇格雷夫斯病所致甲状腺功能亢进症的首选药物。几十年来，这些药物一直是公认的治疗方法，其副作用的总体风险是已知的。自20世纪70年代以来，对于孕期使用ATD，人们一直担心其致畸副作用。近年来，一些大型观察性研究提供了新的证据，并对不同类型ATD相关的出生缺陷风险进行了量化。甲巯咪唑（MMI）和丙硫氧嘧啶（PTU）均与出生缺陷有关这一发现，对孕期甲状腺功能亢进症的临床治疗建议提出了挑战，某些方面仍不明确。在本综述中，描述了早期妊娠使用ATD相关出生缺陷风险的现有证据，并讨论了因果关系的决定因素。这包括生物梯度的现有证据以及母体甲状腺功能本身的作用。最后，讨论了治疗时机和类型的临床方面，并探讨了未来前景。现有证据证实MMI与出生缺陷风险相关，而确定PTU的致畸潜力还需要更多证据。需要对大型队列中的暴露类型和时机进行详细评估。此外，开展研究探索替代或新的治疗方法很有必要。
