Free thyroxine (free T4) is the main hormone of the thyroid gland that circulates in the blood in an unbound, biologically available form. It is the free fraction (about 0.03% of all T4) that reflects the body's real hormonal supply.
T4 itself is a prohormone: in the tissues it is converted into the more active T3. So free T4 is almost always assessed together with TSH — together they show at what level (the pituitary or the gland itself) the problem arose.
Reference ranges
The reference depends on the lab and method; a typical adult range:
| Adults (typical reference) | 9.0 – 19.0 pmol/L |
| In ng/dL units | 0.7 – 1.5 ng/dL |
| Overt hypothyroidism | free T4 reduced, TSH elevated |
| Hyperthyroidism | free T4 elevated, TSH reduced |
| Subclinical forms | free T4 normal, only TSH changed |
What an elevated level means
Elevated free T4 means an excess of thyroid hormone — thyrotoxicosis. TSH is usually reduced.
Common causes: Graves' disease (diffuse toxic goiter), toxic nodular goiter, destructive thyroiditis in the hormone-release phase, levothyroxine overdose, iodine excess (including from amiodarone or contrast).
Symptoms: palpitations and skipped beats, hand tremor, sweating, heat intolerance, anxiety and irritability, weight loss with a normal appetite, sleep disturbances.
What a low level means
Reduced free T4 is a sign of hypothyroidism: the gland does not produce enough hormone. If TSH is elevated at the same time, this is primary hypothyroidism (a problem in the gland itself).
Causes: autoimmune thyroiditis (Hashimoto's) — the most common, a state after surgery or radioiodine therapy, marked iodine deficiency, some medications.
A special variant is central hypothyroidism: free T4 is low while TSH is low or "inappropriately normal". Here the cause is in the pituitary or hypothalamus, not the thyroid.
Symptoms: fatigue, feeling cold, weight gain, dry skin, hair loss, constipation, sluggishness, low mood.
How the test is done
Free T4 is drawn from a vein; strict fasting is not required. It is better to take blood in the morning; if you take levothyroxine — before the morning dose, otherwise the result will be inflated.
The main rule: free T4 is not interpreted in isolation. It is always looked at together with TSH, and if needed — with free T3 and TPO antibodies, to understand both the level and the cause of the disorder.
What affects the value
- Biotin (vitamin B7) in high doses distorts many thyroid tests — stop it 2–3 days before.
- Levothyroxine: taking the drug before the blood draw inflates free T4 — test before the morning dose.
- Pregnancy and estrogen — change the level of binding proteins; free T4 norms in pregnancy differ.
- Severe acute illness — euthyroid sick syndrome (low-T4/T3 syndrome).
- Medications: amiodarone, glucocorticoids, heparin, anticonvulsants (phenytoin, carbamazepine).
- Lab method — direct and calculated free T4 can give different values.
Calculate using this marker
Calculators where Free thyroxine (T4) is used directly:
Frequently asked questions
How does free T4 differ from total T4?
Total T4 includes hormone bound to blood proteins, so it depends on their level (for example, it rises in pregnancy and with estrogen). Free T4 is only the active, unbound fraction; it more accurately reflects thyroid function, so it is the one used in practice.
Free T4 is normal but TSH is changed — what does that mean?
Most often this is a subclinical disorder: the gland still keeps free T4 normal, but the pituitary is already reacting with a change in TSH. Elevated TSH with normal free T4 is subclinical hypothyroidism; reduced TSH with normal free T4 is subclinical hyperthyroidism.
When is it best to test free T4?
In the morning, and if you take levothyroxine — before the dose: a tablet before the test temporarily inflates free T4. For monitoring over time, test under consistent conditions and, if possible, at the same lab.
Related terms
Sources
- Jonklaas J. et al. Guidelines for the Treatment of Hypothyroidism. Thyroid, 2014
- Ross D.S. et al. 2016 ATA Guidelines for Hyperthyroidism. Thyroid, 2016
- MedlinePlus (NIH) — T4 (Thyroxine) Test