Normal T4 Reference Range
The normal reference range for free T4 (FT4) is approximately 0.7-1.9 ng/dL (9-25 pmol/L), though this varies slightly by laboratory and assay method. 1
Standard Reference Ranges
The American Association of Clinical Endocrinologists recommends that normal thyroid lab values include:
- TSH: 0.45-4.5 mIU/L 1
- Free T4: within laboratory-specific reference range 1
- Free T3: within laboratory-specific reference range 1
The TSH reference range of 0.45-4.5 mIU/L is based on NHANES III data from disease-free populations, representing the most widely accepted standard. 1
Important Caveats About T4 Measurement
Assay-Specific Variation
Different laboratory platforms can produce significantly different T4 values for the same patient sample. 2 In documented cases, the same patient's FT4 measured 4.59 ng/dL on Roche® platform versus 1.08 ng/dL on Abbott® platform—both supposedly "normal" by their respective reference ranges. 2 This highlights that you must always interpret T4 values using the specific reference range provided by the laboratory that performed the test.
Clinical Context Matters More Than Isolated Values
TSH is the primary screening test for thyroid dysfunction, not T4. 1 A normal T4 level alone does not exclude thyroid disease—subclinical hypothyroidism is defined as elevated TSH (>4.5 mIU/L) with normal free T4. 1, 3 Approximately 75% of patients with elevated TSH have values <10 mIU/L while maintaining normal T4 levels. 1
Factors That Alter T4 Levels
Non-Thyroidal Illness
Acute illness can cause low T4 without actual thyroid dysfunction. 1 In acute renal failure, both free T4 and total T4 are consistently reduced (mean free T4 5.91 pmol/L, range 1.0-13.1 pmol/L) despite normal TSH levels. 4 This represents sick euthyroid syndrome, not true hypothyroidism.
Medications and Iodine Exposure
- Dopamine, glucocorticoids, and dobutamine can suppress TSH without causing actual hyperthyroidism 1
- Iodine from CT contrast can transiently impact thyroid function tests 5
- Amiodarone can alter thyroid hormone levels 6
Pregnancy
Pregnancy causes physiologically low TSH with normal free hormone levels. 1 This is a normal adaptation and does not indicate hyperthyroidism.
Diagnostic Algorithm
When interpreting T4 results, always measure TSH simultaneously:
- If TSH is elevated (>4.5 mIU/L) with low free T4 → overt primary hypothyroidism 1
- If TSH is suppressed (<0.45 mIU/L) with elevated free T4 and/or free T3 → overt hyperthyroidism 1
- If TSH is elevated with normal free T4 → subclinical hypothyroidism 1
- If TSH is low with normal free T4 → subclinical hyperthyroidism 1
Central Hypothyroidism Exception
Low or normal TSH with low free T4 suggests pituitary or hypothalamic dysfunction (central hypothyroidism). 1 This is the one scenario where TSH fails as a screening test, and you must rely on free T4 levels to detect the problem.
Common Pitfalls
Never interpret T4 values in isolation without TSH. 1 The combination of both tests is required to distinguish between primary thyroid disorders, central disorders, and non-thyroidal illness. 1
Assay interference can produce falsely elevated or decreased T4 values. 2 If T4 results don't match the clinical picture or TSH level, consider testing on a different platform or checking for interfering antibodies (anti-TPO, anti-Tg). 2
In patients on levothyroxine replacement, the free T4 is typically higher than in untreated euthyroid individuals (mean 16 pmol/L vs 14 pmol/L) even when TSH is normalized. 7 This is expected and does not indicate overtreatment if TSH remains in the reference range.