FT4 Reference Ranges by Age
The provided JAMA guideline does not specify age-stratified FT4 reference ranges; it only defines subclinical thyroid disease as conditions where FT4 remains within its reference range while TSH is abnormal, without providing the actual FT4 values by age. 1
What the JAMA Guideline Actually States
The 2004 JAMA guideline on subclinical thyroid disease focuses primarily on TSH reference ranges and defines:
- Subclinical hypothyroidism: TSH above the upper limit with FT4 within its reference range 1
- Subclinical hyperthyroidism: TSH below the lower limit with FT4 and T3 within their reference ranges 1
The guideline explicitly states that FT4 should be "within its reference range" but does not provide specific numerical values or age-stratified ranges for FT4. 1
Critical Interpretation Guidance from Guidelines
Platform-Specific Reference Ranges Are Essential
- Each laboratory must use the reference range established by their specific analyzer and reagent system, as FT4 reference ranges vary significantly between different immunoassay platforms and manufacturers 2, 3
- The American College of Medical Genetics emphasizes using assay-specific ranges to avoid misdiagnosis 2
FT4 Must Be Interpreted with TSH
- FT4 should always be interpreted in conjunction with TSH levels for comprehensive thyroid assessment 2, 3
- In congenital hypothyroidism of thyroidal origin, TSH is elevated with low FT4, while central hypothyroidism shows low FT4 without clearly elevated TSH 2
Age-Related FT4 Patterns from Research Evidence
While the JAMA guideline doesn't provide age-specific FT4 ranges, recent research demonstrates important age-related patterns:
Pediatric Populations
- Neonates (1-4 days): FT4 concentrations are markedly elevated at 48.1 ± 1.5 pmol/L (3.74 ± 0.12 ng/dL) 4
- Infants (2-20 weeks): FT4 decreases to 20.3 ± 0.6 pmol/L (1.58 ± 0.05 ng/dL) 4
- Infants (5-24 months): FT4 further decreases to 17.0 ± 0.4 pmol/L (1.32 ± 0.03 ng/dL) 4
- Children (2-7 years): FT4 increases to 19.9 ± 0.4 pmol/L (1.55 ± 0.03 ng/dL) 4
- Adolescents (8-20 years): FT4 stabilizes at 21.2 ± 0.4 pmol/L (1.65 ± 0.03 ng/dL) 4
Specific Pediatric Reference Intervals
- Day 14-21 of life: 11.59-21.00 pmol/L (2.5th-97.5th percentile) 5
- Day 22-30 of life: 10.14-19.60 pmol/L (2.5th-97.5th percentile) 5
- Children 1-12 months: 1.3-2.8 ng/dL using LC/MS/MS 6
- Children 1-18 years: 1.3-2.4 ng/dL using LC/MS/MS 6
Adult Populations
- FT4 lower reference limits decrease from childhood toward adulthood 7
- FT4 upper reference limits increase from age 70 years onward 7
- The American Association of Clinical Endocrinologists recommends using the laboratory's established reference range for FT4, typically without age adjustment in adults 3
Important Clinical Caveats
Assay Method Matters Significantly
- Reference intervals vary substantially between different manufacturer assays (Roche, Abbott, Siemens, Beckman Coulter) 7, 5
- LC/MS/MS provides tighter reference intervals (1.3-2.4 ng/dL) compared to immunoassay platforms (0.48-2.78 ng/dL for males, 0.85-2.09 ng/dL for females) 6
External Factors Affecting FT4
- Amiodarone can alter thyroid hormone levels 3
- Non-thyroidal illness can cause abnormal thyroid function tests without actual thyroid dysfunction 3
- Iodine exposure from CT contrast can transiently impact thyroid function tests 3