Routine free thyroxine reference intervals are suboptimal for monitoring children on thyroxine replacement therapy and target intervals need to be assay-specific

Elizabeth Wheeler, Kay Weng Choy, Lit Kim Chin, Nilika Wijeratne, Alan McNeil, Tina Yen, Susan Matthews, David Deam, Zhong Lu, Tze Ping Loh, James Doery, Philip Bergman

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Abstract

Central hypothyroidism is a condition where there is (qualitatively or quantitatively) TSH deficiency, leading to reduced thyroid hormone production. In such patients, serum TSH does not accurately reflect the adequacy of thyroxine replacement, as the log-linear relationship between thyrotropin (TSH) and free thyroxine (FT4) is lost. We aimed to prospectively determine the optimal physiological FT4 treatment range for children treated for primary hypothyroidism, based on their serum TSH concentrations. This information could be used to guide optimal therapy for all children on thyroxine replacement, including those with central hypothyroidism. In total, sixty children (median age: 11 years, range: 11 months to 18 years) were recruited over 21 months. They were prescribed a stable dose of thyroxine for at least 6–8 weeks prior to a thyroid function test that consisted of serum TSH, FT4 and free triiodothyronine (FT3) measurements. The serum sample for the thyroid function tests was collected before ingestion of the daily dose, i.e. the trough concentration, and measured using Beckman Coulter UniCel DxI 800 instrument, Siemens Advia Centaur, Roche Cobas, Abbott Architect, Ortho Clinical Diagnostics Vitros 5600 (Ortho-Clinical Diagnostics, Raritan, NJ) platforms. The FT4 and FT3 reference intervals showed significant inter-method difference. The lower limit of the FT4 reference intervals were generally shifted mildly higher when the TSH concentration of the children were restricted from 0.5–5.0 mIU/L to 0.5–2.5 mIU/L. By contrast, the upper limit of the FT3 and FT4 reference intervals were relatively stable for the different TSH concentrations. Assay-specific target ranges for optimal thyroxine therapy are required until FT4 assay standardisation is realised.

Original languageEnglish
Article number19080
Number of pages7
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 13 Dec 2019
Externally publishedYes

Bibliographical note

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Keywords

  • free thyroxine
  • reference intervals
  • replacement therapy
  • children
  • assay-specific

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    Wheeler, E., Choy, K. W., Chin, L. K., Wijeratne, N., McNeil, A., Yen, T., Matthews, S., Deam, D., Lu, Z., Loh, T. P., Doery, J., & Bergman, P. (2019). Routine free thyroxine reference intervals are suboptimal for monitoring children on thyroxine replacement therapy and target intervals need to be assay-specific. Scientific Reports, 9(1), [19080]. https://doi.org/10.1038/s41598-019-55690-x