T4

What is being tested?
This test measures the amount of thyroxine, or T4, in the blood. T4 is one of the two main hormones produced by the thyroid (the other is triiodothyronine, or T3). T4 makes up most of what is called thyroid hormone, while T3 makes up less than 10%. T4 is produced, then bound to a protein called thyroglobulin and stored in the thyroid. When thyroid hormone is needed, the thyroid produces T4 or T3 and/or releases stored T4 into the circulation. In the circulation, T4 is present in free (unbound) form and bound to proteins (mainly thyroxine-binding globulin). Free T4 makes up only 0.1% of total T4, but it is the biologically active form. T4 only becomes active when it is converted to T3 in the blood or other tissues.
If the thyroid gland does not produce enough T4 (because of thyroid dysfunction or insufficient TSH), symptoms of hypothyroidism appear, such as weight gain, dry skin, cold intolerance, irregular periods and weakness. If too much T4 is produced, symptoms of hyperthyroidism appear, such as a faster heart rate, anxiety, weight loss, insomnia, hand tremors, and swollen, irritated eyes.

The most common cause of abnormal thyroid function is autoimmune. Graves’ disease causes hyperthyroidism and Hashimoto’s thyroiditis causes hypothyroidism. Hyperthyroidism and hypothyroidism can also be due to inflammation of the thyroid, thyroid cancer and abnormal TSH production. The effects of these conditions on thyroid hormone production can be detected and followed by measuring total T4 (free plus bound fractions) and free T4 (unbound fraction).

How is the sample collected for testing?
The blood sample is taken from a vein.

How is it used?
When is it requested?
What does the test result mean?
Is there anything else I should know?

How is it used?
Total T4 and free T4 are two separate tests, both useful for assessing thyroid function.
Total T4 was used for many years in the diagnosis of hyperthyroidism and hypothyroidism. Although useful, it is affected by the amount of hormone-binding proteins in the circulation. Because free T4 is the active form of thyroxine, it is considered the most accurate indicator of thyroid hormone activity, and it frequently replaces total T4.
Thyroxine testing is often requested together with TSH to assess whether the feedback regulation system is working properly and to identify the causes of hypothyroidism and hyperthyroidism. T3 is sometimes also requested for further information.
T4 and TSH may be requested to assess a goitre or in the diagnosis of female infertility. If autoimmune thyroid disease is suspected, thyroid antibodies may be requested as well as T4. When monitoring abnormal thyroid function, T4 and/or TSH should be requested. In the case of abnormal thyroid function in pregnancy, T4 and TSH should be requested to detect any hypothyroidism or hyperthyroidism in the fetus.
Newborn screening for T4 and TSH is carried out to detect congenital hypothyroidism, which, if untreated, can cause intellectual disability.

When is it requested?
Total T4 or free T4 is requested when TSH values are abnormal. T4 and TSH are sometimes requested together to assess how well the hormonal feedback system is working.
These tests are requested when there are symptoms typical of hypothyroidism or hyperthyroidism. There is no consensus on their use as screening tests. They are prescribed to monitor the effectiveness of treatment in abnormal thyroid function.
In the case of abnormal thyroid function in pregnancy, they are requested in the early and late stages of pregnancy and also after delivery to monitor the mother and the baby.
Newborn screening is carried out for all babies.

What does the test result mean?
A high free or total T4 value may indicate an overactive gland (hyperthyroidism).
A low free or total T4 value may indicate an underactive gland (hypothyroidism). The test results are not diagnostic in themselves but may prompt a search for the causes of the excess or deficiency. Both increases and decreases in T4 may accompany various chronic or temporary thyroid conditions. Low T4 with low TSH, or high T4 with high TSH, may indicate a disorder of pituitary origin.

The following table summarises the test results and what they may mean:

T4	TSH	T3	Interpretation
Normal	High	Normal	Mild (subclinical) hypothyroidism
Low	High	Low or normal	Hypothyroidism
Normal	Low	Normal	Mild (subclinical) hyperthyroidism
High or normal	Low	High or normal	Hyperthyroidism
Low or normal	Low	Low or normal	Rare pituitary (secondary) hypothyroidism

 
If a patient with hyperthyroidism is being treated and has normal T3 values (or, more often, normal T4 or TSH), the treatment is probably working. If, however, T3 (or T4) values are still high, the treatment is not enough to bring the hormones back to normal levels, and symptoms of hyperthyroidism may persist.

Is there anything else I should know?
Many types of medicine – including oestrogens, certain types of contraceptive and high doses of aspirin – can affect total T4 test results. It is therefore advisable to tell your doctor about any medicines you are taking before the test. In general, free T4 levels are not affected by these types of medicine.

1. How can pregnancy change thyroid hormone levels?

1. How can pregnancy change thyroid hormone levels?
Pregnancy can raise total T4 levels, but this increase does not indicate thyroid disease