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Continuous age-dependent reference ranges for thyroid hormones in neonates, infants, children and adolescents
Ulrich Hübner1, Christine Englisch, Heiko Werkmann
1Department of Clinical Chemistry/Central Laboratory, University Hospital of the Saarland, Homburg/Saar, Germany.
Insights
New reference ranges for thyroid hormones in children were established using continuous age-dependent models. These ranges, including thyroid-stimulating hormone (TSH) and free thyroxine (FT4), are crucial for accurate diagnosis in pediatric endocrinology.
Area of Science:
- Pediatric Endocrinology
- Clinical Chemistry
- Immunoassay Development
Background:
- Thyroid hormone levels in children exhibit significant age-related variations.
- Establishing accurate, age-specific reference ranges is essential for diagnosing thyroid dysfunction in pediatric populations.
- Current reference ranges for the ADVIA Centaur immunoanalyzer are lacking for pediatric age groups.
Purpose of the Study:
- To establish continuous, age-dependent reference ranges for key thyroid hormones in neonates, infants, children, and adolescents.
- To evaluate the performance of the ADVIA Centaur immunoanalyzer for pediatric thyroid hormone measurements.
- To compare newly derived reference ranges with existing published data.
Main Methods:
- Serum samples from 460 healthy children (0-18 years) were analyzed for TSH, FT4, T4, FT3, and T3 using the ADVIA Centaur analyzer.
- Parametric regression techniques were employed to estimate continuous, age-dependent reference ranges (median, upper, and lower limits).
- Statistical analysis was performed to assess age, sex, and residence-specific effects.
Main Results:
- Continuous age-dependent reference ranges demonstrated a better fit to the data compared to discontinuous ranges.
- Median concentrations of TSH and FT4 decreased in the first year of life and stabilized thereafter.
- Median T4 decreased throughout childhood, while FT3 remained constant and T3 increased initially then decreased.
- New ranges for FT3 and TSH differed notably from previously published ranges, highlighting assay-specific variations.
Conclusions:
- Continuous age-dependent reference ranges provide a more accurate reflection of thyroid hormone levels in children.
- Assay-specific evaluation of reference ranges is critical due to the lack of international standardization.
- The established ranges are vital for precise interpretation of thyroid function tests in pediatric patients using the ADVIA Centaur system.
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.