Continuous Age-Dependent Reference Ranges for Thyroid Hormones in Neonates, Infants, Children and Adolescents Established Using the ADVIA(r) Centaur(tm) Analyzer
Abstract
In neonates, infants, children and adolescents serum concentrations of the thyroid hormones show a clear age dependency. Currently, age-dependent thyroid hormone reference ranges for the new ADVIA Centaur immunoanalyzer are not available. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), total thyroxine (T4), free triiodothyronine (FT3) and total triiodothyronine (T3) were determined in the sera of 460 healthy children aged 0 daysto 18 years from an inland (n=308) and a seaside city (n=152) using the Bayer ADVIA Centaur analyzer. Square root functions defining the upper and lower limit of the continuous age-dependent reference range and the median line for each thyroid hormone were estimated applying a parametric regression technique. Continuous age-dependent reference ranges show a better fit to the obtained data than discontinuous reference ranges. The median TSH and FT4 concentrations decrease within the first year of life and are nearly constant until 18 years of age. The median T4 decreases within the entire age interval, whereas the median FF3 is constant. The median T3 increases within the first year of life and decreases afterwards. The calculated continuous reference ranges for T4, T3 and partly FT4 are consistent with published reference ranges. However, the reference ranges obtained for FT3 and partly TSH differed considerably, compared to published reference ranges. No significant residence- or sex-specific effects on age-adjusted hormone concentrations were found except for a slight residence-specific effect on age-adjusted FT4, which was probably due to assay imprecision. Due to the lack of international standardization, the assay-specific evaluation of reference ranges is very important. Continuous age-dependent reference ranges comply better with the biological reality and are more reliable than discontinuous reference ranges.
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Small studies in children indicate marked variation in thyroid hormone reference ranges such that adult reference intervals are not universally applicable to children.
“Small studies in children indicate marked variation in thyroid hormone reference ranges such that adult reference intervals are not universally applicable to children [33–35].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [34]
Cites
Influence of statistical method used on the resulting estimate of normal range.
Reed, A. H., Henry, R. J., & Mason, W. B. (1971) · Clinical Chemistry · doi:10.1093/clinchem/17.4.275 · Cited by 598 · see citing works
Construction of age‐related reference centiles using absolute residuals
Altman, D. G. (1993) · Statistics in Medicine · doi:10.1002/sim.4780121003 · Cited by 296 · see citing works
Age-related changes in serum free thyroxine during childhood and adolescence
Nelson, J. C., Clark, S. J., Borut, D., Tomei, R. T., & Carlton, E. I. (1993) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)80385-3 · Cited by 87 · see citing works
Soldin, S. J., Morales, A., Albalos, F., et al. (1995) · Clinical Biochemistry · doi:10.1016/0009-9120(95)00038-5 · Cited by 71 · see citing works
Evaluation of the ADVIA® Centaur™ TSH-3 Assay
Vogeser, M., Weigand, M., Fraunberger, P., Fischer, H., & Cremer, P. (2000) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2000.048 · Cited by 10 · see citing works
Liappis, N., Schlebusch, H., Perjés, M., et al. (1991) · Klinische Pädiatrie · doi:10.1055/s-2007-1025411 · Cited by 4 · see citing works
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Kapelari, K., Kirchlechner, C., Högler, W., Schweitzer, K., Virgolini, I., & Moncayo, R. (2008) · BMC Endocrine Disorders · doi:10.1186/1472-6823-8-15 · Cited by 203 · see citing works
Taylor, P. N., Lansdown, A., Witczak, J., Khan, R., Rees, A., Dayan, C. M., & Okosieme, O. (2023) · Thyroid Research · doi:10.1186/s13044-023-00149-5 · Cited by 72 · see citing works
Önsesveren, I., Barjaktarovic, M., Chaker, L., de Rijke, Y. B., Jaddoe, V. W. V., van Santen, H. M., Visser, T. J., Peeters, R. P., & Korevaar, T. I. M. (2017) · Thyroid® · doi:10.1089/thy.2017.0262 · Cited by 58 · see citing works
Trisomy 21 Causes Persistent Congenital Hypothyroidism Presumably of Thyroidal Origin
Trotsenburg, A. S. P. V., Kempers, M. J. E., Endert, E., Tijssen, J. G. P., Vijlder, J. J. M. D., & Vulsma, T. (2006) · Thyroid · doi:10.1089/thy.2006.16.671 · Cited by 53 · see citing works
Taylor, P. N., Sayers, A., Okosieme, O., Das, G., Draman, M. S., Tabasum, A., Abusahmin, H., Rahman, M., Stevenson, K., Groom, A., et al. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-3605 · Cited by 34 · see citing works
Reference range of thyroid hormones in normal Indian school‐age children
Marwaha, R. K., Tandon, N., Desai, A., Kanwar, R., Grewal, K., Aggarwal, R., Sastry, A., Singh, S., Ganguly, S. K., & Mani, K. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.03048.x · Cited by 31 · see citing works
- Authors
- Hübner, U., Englisch, C., Werkmann, H., Butz, H., Georg, T., Zabransky, S., & Herrmann, W.
- Affiliations
- Universitätsklinikum des Saarlandes (DE)
- ORCID
- Georg, Thomas
- Venue
- Clinical Chemistry and Laboratory Medicine
- Publisher
- Walter de Gruyter GmbH
- Published
- 2002-01-29
- Volume
- 40
- Issue
- 10
- Pages
- 1040-7
- ISSN
- 1434-6621 (ISSN-L)
- OpenAlex
- W2079120837
- Cited by
- 52
- References
- 6
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 1 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 7 · 2012: 1
- FWCI
- 0.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Chemistry and Laboratory Medicine (CCLM) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bayer Vital
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- thyroid hormones, thyroid-stimulating hormone, free thyroxine, total thyroxine, free triiodothyronine, total triiodothyronine, neonates, children, adolescents, parametric regression, coastal vs inland populations
- MeSH terms
- Adolescent, Age Factors, Child, Child, Preschool, Female, Humans, Immunoassay, Infant, Infant, Newborn, Male, Reference Standards, Sex Factors, Thyroid Hormones, Thyrotropin, Thyroxine, Triiodothyronine
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