Therapeutic drug monitoring during pregnancy and lactation: thyroid function assessment in pregnancy-challenges and solutions.
Therapeutic drug monitoring during pregnancy and lactation: thyroid function assessment in pregnancy-challenges and solutions.
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妊娠期和哺乳期治疗药物监测：妊娠期甲状腺功能评估——挑战与解决方案。
DOI：
10.1097/ftd.0b013e3181ddf729
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发表时间：
2010
影响因子：
2.5
通讯作者：
Soldin,OffieP
中科院分区：
文献类型：
--
作者：
Soldin,OffieP
甲状腺疾病的诊断和监测需要了解甲状腺病理生理学和目前与甲状腺有关的生化测试的技术局限性。由于与妊娠相关的甲状腺激素代谢变化，妊娠和哺乳期甲状腺疾病的诊断和监测进一步复杂化。妊娠期甲状腺激素和三碘甲腺原氨酸水平的剧烈变化对甲状腺功能减退孕妇构成了挑战。在怀孕早期，需要增加左旋甲状腺素的替代。此外，增加甲状腺激素替代需要个别和及时地进行。原因尚不完全清楚，尽管部分依赖于甲状腺激素结合的变化，但随着妊娠的进展，游离甲状腺激素(FT4)水平下降，有必要使用特定于三个月的参考间隔进行适当的替代。甲状腺激素结合蛋白水平因激素状态、遗传和疾病状态的不同而不同，在怀孕时水平较高；因此，FT4分析因其测量非结合激素而流行起来。然而，目前的FT4免疫分析是不可靠地测量FT4的估计性测试，并且已知对结合蛋白的变化敏感，因此是特定于方法的。在胎儿甲状腺功能之前，需要可靠地识别出低甲状腺素血症的孕妇，特别是在妊娠的前三个月，这对于胎儿大脑的早期发育是至关重要的。本文涉及1)目前非实验室甲状腺激素免疫分析方法的局限性，特别是在妊娠期间的局限性；2)甲状腺功能检测的三个月特定的参考间隔；以及3)怀孕和非怀孕妇女的左旋甲状腺素药代动力学研究。
The diagnosis and monitoring of thyroid disease necessitates the knowledge of thyroid pathophysiology and of the technical limitations of current thyroid-related biochemical tests. Thyroid disease diagnosis and monitoring are further complicated during pregnancy and lactation, due to pregnancy-related changes in thyroid hormone metabolism. Dramatic changes that occur in thyroxine and triiodothyronine ranges during pregnancy pose challenges for hypothyroid gravidas. Very early in pregnancy, levothyroxine replacement needs to be increased. Moreover, increases in thyroid hormone replacement need to be conducted individually and on a timely basis. For reasons that are still not entirely clear, although dependent in part on changes in thyroxine binding, free thyroxine (FT4) levels decrease as pregnancy progresses necessitating the use of trimester-specific reference intervals for appropriate replacement. Thyroxine binding protein levels vary by hormonal status, inheritance, and disease states and are higher in pregnancy; hence, FT4 assays became popular because they measure the unbound hormone. However, current FT4 immunoassays are estimate tests that do not reliably measure FT4 and are known to be sensitive to alterations in binding proteins and therefore are method-specific. The need to reliably identify hypothyroxinemic pregnant patients, especially in the first trimester, is of prime importance for early fetal brain development before the fetal thyroid functions. This article addresses 1) the current limitations of laboratory-free thyroxine immunoassay methodologies and especially during pregnancy; 2) trimester-specific reference intervals for thyroid function tests; and 3) the study of levothyroxine pharmacokinetics in pregnant and nonpregnant women.