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Stroek K, Heijboer AC, van Veen-Sijne M, et al. Improving the Dutch Newborn Screening for Central Congenital Hypothyroidism by Using 95% Reference Intervals for Thyroxine-Binding Globulin. Eur Thyroid J. 2021;10(3):222-229doi: 10.1159/000513516.
Stroek, K., Heijboer, A. C., van Veen-Sijne, M., Bosch, A. M., van der Ploeg, C. P. B., Zwaveling-Soonawala, N., de Jonge, R., van Trotsenburg, A. S. P., & Boelen, A. (2021). Improving the Dutch Newborn Screening for Central Congenital Hypothyroidism by Using 95% Reference Intervals for Thyroxine-Binding Globulin. European thyroid journal, 10(3), 222-229. https://doi.org/10.1159/000513516
Stroek, Kevin, et al. "Improving the Dutch Newborn Screening for Central Congenital Hypothyroidism by Using 95% Reference Intervals for Thyroxine-Binding Globulin." European thyroid journal vol. 10,3 (2021): 222-229. doi: https://doi.org/10.1159/000513516
Stroek K, Heijboer AC, van Veen-Sijne M, Bosch AM, van der Ploeg CPB, Zwaveling-Soonawala N, de Jonge R, van Trotsenburg ASP, Boelen A. Improving the Dutch Newborn Screening for Central Congenital Hypothyroidism by Using 95% Reference Intervals for Thyroxine-Binding Globulin. Eur Thyroid J. 2021 Jun;10(3):222-229. doi: 10.1159/000513516. Epub 2021 Mar 05. PMID: 34178708; PMCID: PMC8215938.
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Eur Thyroid J. 2021 Jun;10(3):222-229. doi: 10.1159/000513516. Epub 2021 Mar 05.

Improving the Dutch Newborn Screening for Central Congenital Hypothyroidism by Using 95% Reference Intervals for Thyroxine-Binding Globulin.

European thyroid journal

Kevin Stroek, Annemieke C Heijboer, Marja van Veen-Sijne, Annet M Bosch, Catharina P B van der Ploeg, Nitash Zwaveling-Soonawala, Robert de Jonge, A S Paul van Trotsenburg, Anita Boelen

Affiliations

  1. Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
  2. Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
  3. Division of Metabolic Disorders, Department of Pediatrics, Emma Children's Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
  4. Department of Child Health, Netherlands Organization for Applied Scientific Research TNO, Leiden, The Netherlands.
  5. Department of Paediatric Endocrinology, Emma Children's Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
  6. Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit & University of Amsterdam, Amsterdam, The Netherlands.

PMID: 34178708 PMCID: PMC8215938 DOI: 10.1159/000513516

Abstract

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 & 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 (<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.

Copyright © 2021 by S. Karger AG, Basel.

Keywords: Central congenital hypothyroidism; Newborn screening; Reference intervals; Thyroxine; Thyroxine-binding globulin

Conflict of interest statement

Annet M. Bosch has received a speaker's fee from Nutricia and has been a member of advisory boards for Biomarin. All other authors have no conflicts of interest to declare.

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