Effects of propylthiouracil and methimazole on fetal thyroid status in mothers with Graves' hyperthyroidism
Effects of propylthiouracil and methimazole on fetal thyroid status in mothers with Graves' hyperthyroidism
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DOI：
10.1210/jc.82.11.3633
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发表时间：
1997-11-01
影响因子：
5.8
通讯作者：
Ito, K
中科院分区：
文献类型：
--
作者：
Momotani, N;Noh, JY;Ito, K
硫代酰胺治疗是妊娠合并甲状腺功能亢进症的主要治疗方法，但它可能使胎儿暴露于甲状腺功能减退症。在胎儿甲状腺状态方面，基于有限经胎盘通过的实验数据，丙基硫氧嘧啶（PTU）优于甲巯咪唑（MMI），并推荐较低剂量。然而，这两种做法都没有令人信服的临床证据支持。我们比较了母亲摄入PTU与MMI对胎儿甲状腺状态的影响，使用脐带血清在分娩时在77名母亲与Graves'甲亢谁正在接受硫代酰胺，其游离T-4（FT 4）水平在正常范围内。我们还研究了剂量对这些妇女胎儿甲状腺状态的影响。P组34例，MMI组43例，两组胎儿FT 4、TSH水平差异均无统计学意义。P组和M组之间低FT 4水平或高胎儿TSH水平的发生率无显著差异（低FT 4，6% vs. 7%;高TSH，21% vs. 14%）。母体剂量和胎儿甲状腺状态之间几乎没有关系;事实上，当给予低剂量PTU（每日100 mg或更少）和MMI（每日10 mg或更少）时，分别在34只胎儿中的7只（21%）和43只胎儿中的6只（14%）中观察到胎儿的TSH水平升高。高剂量与正常或低的胎儿TSH水平有关，这些发现表明，就胎儿甲状腺功能低下的诱发潜力而言，没有理由选择PTU而不是MMI。个体化，而不是统一的低剂量，这些药物可以预防胎儿甲状腺功能减退症。
Thionamide therapy is a mainstay of the treatment of hyperthyroidism complicated by pregnancy, but it can expose the fetus to hypothyroidism. In terms of fetal thyroid status, propylthiouracil (PTU) has been preferred over methimazole (MMI) based on experimental data on limited transplacental passage, and lower doses have been recommended. However, neither of these practices is supported by convincing clinical evidence.We compared the effect of maternal ingestion of PTU with that of MMI on fetal thyroid status using cord sera at delivery in 77 mothers with Graves' hyperthyroidism who were receiving thionamides and whose free T-4(FT4) levels were within the normal range. We also examined the dose effects on fetal thyroid status in these women. Thirty-four women were taking PTU (group P), and 43 were taking MMI (group M).Neither the mean fetal FT4 nor the mean fetal TSH level was significantly different between the two groups. No significant difference in the occurrence of low FT4 levels or high fetal TSH levels was found between group P and group M (low FT4, 6% vs. 7%; high TSH, 21% vs. 14%). Little relationship was observed between maternal doses and fetal thyroid status; in fact, when low doses of both PTU (100 mg daily or less) and MMI (10 mg daily or less) were administered, high TSH levels in the fetus were observed in 7 of the 34 fetuses (21%) and in 6 of the 43 fetuses (14%), respectively. Higher doses were associated with normal or low fetal TSH levels.These findings demonstrate that in terms of fetal hypothyroidism-inducing potential, there is little reason to choose PTU over MMI. Individualized, not uniformly low, doses of these drugs may prevent fetal hypothyroidism.