Childhood Thyroid Function Reference Ranges and Determinants: A Literature Overview and a Prospective Cohort Study

Area of Science:

• Pediatric endocrinology
• Clinical chemistry
• Reference range establishment

Background:

• Reported reference ranges for childhood thyroid-stimulating hormone (TSH) and free thyroxine (fT4) exhibit significant variability.
• Existing knowledge on factors influencing thyroid function in children is limited.

Purpose of the Study:

• To systematically review existing literature on childhood TSH and fT4 reference ranges.
• To identify determinants of TSH and fT4 concentrations in a pediatric cohort.
• To assess the impact of these determinants on reference range calculations.

Main Methods:

• Systematic literature search of major scientific databases (PubMed, Embase, etc.) for thyroid function reference ranges in children.
• Analysis of a prospective cohort of 4273 children (median age 6.0 years) to examine associations between TSH/fT4 levels and factors like age, sex, anthropometrics, ethnicity, maternal education, and venipuncture timing.
• Investigation into how individual variations in determinants affect reference range calculations.

Main Results:

• Published TSH and fT4 reference ranges show substantial differences across and within age groups.
• In the study cohort, weight, sex, and ethnicity were significant determinants for both TSH and fT4.
• Height and time of venipuncture influenced TSH levels, while minimal association was observed between TSH and fT4.
• Determinants accounted for considerable variation in reference range cutoffs for TSH and fT4.

Conclusions:

• Significant discrepancies exist in established childhood TSH and fT4 reference ranges.
• Factors such as weight, sex, and ethnicity are crucial determinants of thyroid function in children.
• These identified determinants explain a substantial portion of the variability observed in pediatric thyroid reference ranges.