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.

译文

:甲状腺疾病的诊断和监测需要了解甲状腺病理生理知识以及当前甲状腺相关生化检查的技术局限性。由于怀孕相关的甲状腺激素代谢变化,甲状腺疾病的诊断和监测更加复杂。怀孕期间甲状腺素和三碘甲状腺素范围内发生的戏剧性变化对甲状腺功能减退症提出了挑战。在怀孕的早期,需要增加左甲状腺素的替代。而且,甲状腺激素替代物的增加需要单独且及时地进行。由于尚不完全清楚的原因,尽管部分取决于甲状腺素结合的变化,但是随着怀孕的进行,游离甲状腺素(FT4)的水平会降低,因此必须使用孕中期特定的参考间隔进行适当的替代。甲状腺激素结合蛋白的水平随激素状态,遗传和疾病状态的不同而变化,并且在怀孕时较高。因此,FT4测定法很受欢迎,因为它们可以测量未结合的激素。但是,当前的FT4免疫测定是不能可靠地测量FT4的估计测试,已知对结合蛋白的变化敏感,因此具有方法特异性。对于胎儿甲状腺功能之前的胎儿大脑早期发育,尤其是在妊娠的头三个月中,可靠地确定甲状腺功能低下的孕妇的需求至关重要。本文解决了以下问题:1)目前无实验室甲状腺素免疫测定方法学的局限性,尤其是在怀孕期间; 2)甲状腺功能检查的妊娠中期参考间隔; 3)孕妇和非孕妇中左甲状腺素的药代动力学研究。

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