Introduction: Newborn screening (NBS) for congenital hypothyroidism (CH) in the Netherlands consists of thyroxine (T4), thyroid-stimulating hormone (TSH), and T4-binding globulin (TBG) measurements to detect thyroidal CH and central CH (CH-C). CH-C is detected by T4 or a calculated T4/TBG ratio, which serves as an indirect measure of free T4. TSH and TBG are only measured in the lowest 20 and 5% of daily T4 values, respectively. A recent evaluation of the Dutch NBS for CH showed that the T4 and T4/TBG ratio contribute to the detection of CH-C but also lead to a low positive predictive value (PPV). Dried blood spot (DBS) reference intervals (RIs) are currently unknown and may contribute to improvement of our NBS algorithm. Materials and Methods: RIs of T4, TSH, TBG, and the T4/TBG ratio were determined according to Clinical amp; Laboratory Standards Institute guidelines in heel puncture cards from routine NBS in both sexes and at the common NBS sampling ages. Scatter plots were used to compare the healthy reference population to previously published data of CH-C patients and false positives. Results: Analyses of 1,670 heel puncture cards showed small differences between subgroups and led to the formulation of total sample DBS RIs for T4 (56–118 nmol/L), TSH (#x3c;2.6 mIU/L), TBG (116–271 nmol/L), and the T4/TBG ratio (#x3e;20). 46% of false-positive referrals based on T4 alone had a TBG below the RI, indicating preventable referral due to partial TBG deficiency. One case of CH-C also had partial TBG deficiency (TBG 59 and T4 12 nmol/L blood). Discussion/Conclusion: Established DBS RIs provided possibilities to improve the PPV of the Dutch CH NBS algorithm. We conclude that by taking partial TBG deficiency into account, approximately half of T4 false-positive referrals may be prevented while maintaining NBS sensitivity at the current level.
Eur Thyroid J

中文翻译：

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使用 95% 的甲状腺素结合球蛋白参考区间改善荷兰新生儿中枢性先天性甲状腺功能减退症的筛查

简介：荷兰的先天性甲状腺功能减退症 (CH) 新生儿筛查 (NBS) 包括甲状腺素 (T4)、促甲状腺激素 (TSH) 和 T4 结合球蛋白 (TBG) 测量，以检测甲状腺 CH 和中枢性 CH (CH- C）。CH-C 通过 T4 或计算出的 T4/TBG 比值检测，作为游离 T4 的间接测量。TSH 和 TBG 分别仅在每日 T4 值的最低 20% 和 5% 中测量。最近荷兰国家统计局对 CH 的评估表明，T4 和 T4/TBG 比率有助于检测 CH-C，但也会导致低阳性预测值 (PPV)。干血斑 (DBS) 参考区间 (RI) 目前未知，可能有助于改进我们的 NBS 算法。材料和方法：T4、TSH、TBG 的 RI 和 T4/TBG 比值根据临床 amp 确定；实验室标准协会在两性和常见 NBS 采样年龄的常规 NBS 足跟穿刺卡中的指南。散点图用于将健康参考人群与先前公布的 CH-C 患者和假阳性数据进行比较。结果： 1,670脚跟穿刺卡分析表明亚组之间的小差异，导致总样品的RI DBS为T4（56-118纳摩尔/ L），TSH的制剂（＃X3C; 2.6 MIU / L），TBG（116-271 nmol/L) 和 T4/TBG 比率 (#x3e;20)。46% 仅基于 T4 的假阳性转诊的 TBG 低于 RI，表明由于部分 TBG 缺乏而可预防转诊。1 例 CH-C 也有部分 TBG 缺乏症（TBG 59 和 T4 12 nmol/L 血液）。讨论/结论：已建立的 DBS RI 为改进荷兰 CH NBS 算法的 PPV 提供了可能性。我们得出的结论是，通过考虑部分 TBG 缺陷，可以防止大约一半的 T4 假阳性转诊，同时将 NBS 敏感性保持在当前水平。
欧洲甲状腺杂志