Stroek Kevin, Heijboer Annemieke C, van Veen-Sijne Marja, Bosch Annet M, van der Ploeg Catharina P B, Zwaveling-Soonawala Nitash, de Jonge Robert, van Trotsenburg A S Paul, Boelen Anita
Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
Eur Thyroid J. 2021 Jun;10(3):222-229. doi: 10.1159/000513516. Epub 2021 Mar 5.
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.
RIs of T4, TSH, TBG, and the T4/TBG ratio were determined according to Clinical & 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.
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 (<2.6 mIU/L), TBG (116-271 nmol/L), and the T4/TBG ratio (>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.
荷兰先天性甲状腺功能减退症（CH）的新生儿筛查（NBS）包括测量甲状腺素（T4）、促甲状腺激素（TSH）和甲状腺素结合球蛋白（TBG），以检测甲状腺性CH和中枢性CH（CH-C）。CH-C通过T4或计算得出的T4/TBG比值来检测，该比值可间接衡量游离T4。TSH和TBG仅分别在每日T4值最低的20%和5%中进行测量。最近对荷兰CH的NBS评估表明，T4和T4/TBG比值有助于检测CH-C，但也导致阳性预测值（PPV）较低。干血斑（DBS）参考区间（RIs）目前尚不清楚，可能有助于改进我们的NBS算法。
根据临床与实验室标准协会指南，在男女常规NBS的足跟穿刺卡片以及常见的NBS采样年龄下，确定T4、TSH、TBG和T4/TBG比值的RIs。使用散点图将健康参考人群与先前发表的CH-C患者和假阳性数据进行比较。
对1670张足跟穿刺卡片的分析显示，各亚组之间存在微小差异，并得出了T4（56 - 118 nmol/L）、TSH（<2.6 mIU/L）、TBG（116 - 271 nmol/L）和T4/TBG比值（>20）的总样本DBS RIs。仅基于T4的假阳性转诊病例中，46%的患者TBG低于RI，表明因部分TBG缺乏导致可预防的转诊。1例CH-C患者也存在部分TBG缺乏（TBG为59，血液中T4为12 nmol/L）。
讨论/结论：既定的DBS RIs为提高荷兰CH NBS算法的PPV提供了可能性。我们得出结论，通过考虑部分TBG缺乏，在将NBS敏感性维持在当前水平的同时，大约一半的T4假阳性转诊可能被避免。
