Correct neonatal free thyroxine reference intervals are crucial to detect central congenital hypothyroidism.
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2026
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Abstract
Abstract Objective In the Netherlands, after an abnormal newborn screening (NBS) result suggestive of central congenital hypothyroidism (CH), children are referred for confirmatory plasma free thyroxine (fT4) measurement. Correct interpretation of these results relies on appropriate age- and assay-specific reference intervals (RI), which are often not available. The current study was performed to check whether the use of adult or other incorrect fT4 RIs during the post-screening work-up of neonates with an abnormal NBS had led to missed diagnoses of central CH. Design Retrospective cohort study with prospective re-evaluation. Methods Children born between 1st of March 2018 and 1st of April 2021 with an abnormal NBS result suggesting central CH were identified through the Dutch national screening registry (NEORAH). Children classified as having a ‘false positive’ screening result based on post-screening confirmatory fT4 concentrations in the neonatal period were included if those fT4 concentrations were ≤ 3 pmol/L above the assay-specific lower limit of the adult RI. After obtaining informed consent, re-evaluation of thyroid function was performed. Results Six children were identified and informed consent was obtained from four participants. Two out of four participants received a new diagnosis of central CH including one case of multiple pituitary hormone deficiencies (MPHD). Conclusions This study highlights the critical need for age- and assay-specific RIs for plasma fT4 to accurately diagnose central CH in the neonatal period.
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| Authors | Mark R. Garrelfs, Peter Lauffer, Jacquelien J Hillebrand, Annemieke C. Heijboer, Anita Boelen, A S Paul van Trotsenburg, Nitash Zwaveling‐Soonawala |
| Journal | european journal of endocrinology |
| Year | 2026 |
| DOI |
10.1093/ejendo/lvag090
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| URL | |
| Keywords | Keywords not found |
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