Normal Free T4 Reference Range
The normal reference range for free T4 (FT4) is laboratory-specific, but typically falls between approximately 12-22 pmol/L (or 0.9-1.7 ng/dL in conventional units), with individual laboratories required to establish their own reference ranges using appropriate quality control procedures. 1
Standard Reference Range
Free T4 concentrations within the reference range, combined with normal TSH (0.45-4.5 mIU/L), indicate euthyroid status in most clinical contexts. 1
The reference range represents the 2.5th to 97.5th percentile of values from a disease-free population, though this statistical definition has important limitations for individual patients. 1
Critical Interpretive Considerations
Individual Variation vs. Population Norms
Each person has a unique thyroid "set point" within the population reference range, with individual 95% confidence intervals approximately half the width of the laboratory reference range. 2
A free T4 result within the laboratory reference range is not necessarily normal for a specific individual—their personal baseline may differ significantly. 2
Significant individual changes can occur while remaining within the broad population reference range, which is why TSH provides logarithmically amplified sensitivity to detect these personal deviations. 2
Context-Dependent Interpretation
In primary hypothyroidism on levothyroxine replacement:
- Patients adequately replaced typically have free T4 in the mid-to-upper normal range (median 16 pmol/L, with 20th-80th percentile of 14-19 pmol/L). 3
- Despite normal TSH, these patients often have higher free T4 and lower free T3 compared to untreated euthyroid individuals. 4
In central (secondary) hypothyroidism:
- Free T4 is generally clearly low when TSH is inappropriately normal or mildly elevated. 1
- The combination of low free T4 with normal TSH is inconsistent with primary hypothyroidism and suggests pituitary or hypothalamic dysfunction. 5
In critical illness (euthyroid sick syndrome):
- Free T4 measured by equilibrium dialysis or ultrafiltration of undiluted serum typically remains normal or elevated despite low total T4. 6
- This distinguishes critically ill euthyroid patients from those with true hypothyroidism. 6
In thyrotoxicosis:
- High free T4 with low or normal TSH indicates thyrotoxicosis, whether from thyroiditis or Graves' disease. 1
Important Clinical Pitfalls
Laboratory method matters: Assays must use appropriate quality control, and each laboratory should independently establish functional sensitivity and reference ranges. 1
Single measurements are insufficient: Confirm abnormal findings with repeat testing over 3-6 months, particularly in asymptomatic individuals. 7
T3 measurement adds little value in levothyroxine-treated patients: Normal T3 can occur even in over-replaced patients, making it unreliable for assessing adequacy of replacement. 8
Timing of testing: For suspected hypophysitis or central hypothyroidism, testing should ideally be conducted in the morning around 8 AM before steroid administration. 1
When both adrenal insufficiency and hypothyroidism are present, always start steroids before thyroid hormone replacement to avoid precipitating adrenal crisis. 1