Free Thyroxine
Free T4· also: Free T4, fT4
Clinical Overview
Free T4 is the active, unbound form of thyroxine (T4) and represents only ~0.03% of total T4. Unlike total T4, free T4 is not affected by changes in binding proteins (TBG), making it a more accurate reflection of thyroid hormone status. Low Free T4 with high TSH confirms hypothyroidism; high Free T4 with low TSH confirms hyperthyroidism.
Why This Test Matters
Free T4 is the essential complement to TSH for confirming thyroid dysfunction and grading its severity. In primary hypothyroidism: TSH is high + FT4 is low (overt) or TSH is high + FT4 is normal (subclinical). In hyperthyroidism: TSH is suppressed + FT4 is high (overt) or TSH is suppressed + FT4 is normal (subclinical, may be T3 thyrotoxicosis). FT4 monitoring during levothyroxine therapy targets the mid-normal range.
Reference RangesWHO/IFCC standards
| Age Group | Reference Range | Unit | Notes |
|---|---|---|---|
| Adults (18–64) | 0.8 – 1.8 | ng/dL | — |
Also reported in: pmol/L.Conversion factor: 1 pmol/L = 12.870 ng/dL.
What Causes Abnormal Results?
High Free T4 Causes
- Graves' disease
- Toxic multinodular goiter
- Toxic thyroid adenoma
- Thyroiditis (transient: Hashimoto thyroiditis "storm", subacute, postpartum)
- Excess levothyroxine therapy
- Amiodarone (contains iodine, can cause thyrotoxicosis or hypothyroidism)
Low Free T4 Causes
- Hashimoto's thyroiditis (most common cause of primary hypothyroidism)
- Post-radioiodine therapy
- Post-thyroidectomy
- Severe iodine deficiency
- Central hypothyroidism (pituitary or hypothalamic disease)
- Non-thyroidal illness (sick euthyroid)
Signs & Symptoms to Watch For
How to Prepare for This Test
No fasting required. Avoid biotin supplements 24 hours before. Ideally, check FT4 at the same time as TSH.
Factors That Can Affect Results
- Biotin supplements (interferes with FT4 immunoassays)
- Pregnancy (FT4 assays may be unreliable; direct dialysis methods preferred)
- Severe non-thyroidal illness (sick euthyroid — FT4 may be low despite normal thyroid)
- Heparin (displaces T4 from binding proteins in vitro)
- Amiodarone (inhibits T4 to T3 conversion, raises FT4)
Related Topics
Frequently Asked Questions
What is the difference between free T4 and total T4?
Total T4 measures all thyroxine — both the fraction bound to proteins (mainly TBG) and the tiny free fraction. Free T4 measures only the biologically active unbound fraction. Because most T4 is bound to TBG, conditions that raise or lower TBG (pregnancy, oral contraceptives, liver disease) can dramatically change total T4 without changing free T4 or thyroid function. Free T4 is always preferred for clinical assessment.