Related Experiment Video
Updated: Jun 21, 2026

Generation of a Mouse Spontaneous Autoimmune Thyroiditis Model
Published on: March 17, 2023
Pediatric reference intervals for free thyroxine and free triiodothyronine
Offie P Soldin1, Megan Jang, Tiedong Guo
1Department of Oncology, Georgetown University Medical Center, Washington, DC 20007, USA. os35@georgetown.edu
Insights
This study establishes new, precise reference intervals for free thyroxine (FT4) and free triiodothyronine (FT3) in children aged 0-18 years. These findings, determined by LC/MS/MS, offer a more accurate assessment of thyroid function in pediatric populations.
Area of Science:
- Pediatric Endocrinology
- Clinical Chemistry
- Mass Spectrometry
Background:
- Accurate reference intervals for thyroid hormones free thyroxine (FT4) and free triiodothyronine (FT3) are crucial for clinical diagnosis in children.
- Existing reference intervals may lack precision, impacting the interpretation of thyroid function tests.
Purpose of the Study:
- To establish age- and sex-specific reference intervals for FT4 and FT3 in neonates, infants, and children up to 18 years of age.
- To utilize tandem mass spectrometry for precise quantification of these thyroid hormones.
Main Methods:
- Serum samples from 1426 children (FT4) and 1107 children (FT3) were analyzed.
- Isotope dilution liquid chromatography tandem mass spectrometry (LC/MS/MS) with deuterium-labeled internal standards was employed.
- Data were collected from healthy children between January 2008 and June 2008.
Main Results:
- FT4 reference intervals were similar across ages and sexes, ranging from 1.3-2.4 ng/dL (1-18 years) and 1.3-2.8 ng/dL (1-12 months).
- LC/MS/MS yielded significantly tighter FT4 intervals compared to immunoassay methods.
- FT3 intervals were consistent across ages and sexes, approximately 1.5-6.0 pg/mL (1 month-18 years).
Conclusions:
- This study provides the first pediatric reference intervals for FT4 and FT3 (birth to 18 years) using LC/MS/MS.
- LC/MS/MS offers more specific and accurate quantification of thyroid hormones.
- The LC/MS/MS method demonstrated excellent correlation with equilibrium dialysis.
Background:
The clinical value of free thyroxine (FT(4)) and free triiodothyronine (FT(3)) analysis depends on the reference intervals with which they are compared. We determined age- and sex-specific reference intervals for neonates, infants, and children 0-18 years of age for FT(4) and FT(3) using tandem mass spectrometry.
Methods:
Reference intervals were calculated for serum FT(4) (n = 1426) and FT(3) (n = 1107) obtained from healthy children between January 1, 2008, and June 30, 2008, from Children's National Medical Center and Georgetown University Medical Center Bioanalytical Core Laboratory, Washington, DC. Serum samples were analyzed using isotope dilution liquid chromatography tandem mass spectrometry (LC/MS/MS) with deuterium-labeled internal standards.
Results:
FT(4) reference intervals were very similar for males and females of all ages and ranged between 1.3 and 2.4 ng/dL for children 1 to 18 years old. FT(4) reference intervals for 1- to 12-month-old infants were 1.3-2.8 ng/dL. These 2.5 to 97.5 percentile intervals were much tighter than reference intervals obtained using immunoassay platforms 0.48-2.78 ng/dL for males and 0.85-2.09 ng/dL for females. Similarly, FT(3) intervals were consistent and similar for males and females and for all ages, ranging between 1.5 pg/mL and approximately 6.0 pg/mL for children 1 month of age to 18 years old.
Conclusions:
This is the first study to provide pediatric reference intervals of FT(4) and FT(3) for children from birth to 18 years of age using LC/MS/MS. Analysis using LC/MS/MS provides more specific quantification of thyroid hormones. A comparison of the ultrafiltration tandem mass spectrometric method with equilibrium dialysis showed very good correlation.
Related Concept Videos
Synthesis and Regulation of Thyroid Hormones
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
Hyperthyroidism I: Introduction
Pharmacokinetics in Pediatric Patients: Drug Distribution
Functions of Thyroid Hormones
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
Pharmacokinetics in Pediatric Patients: Drug Metabolism
Drug Dosing: Infants and Children
