Thyroxine (T4), Free, Direct

Thyroxine (T4), Free, Direct


SKU: 1974 Category:


Also known as:

T4; Thyroxine

Formal name:

Free Thyroxine

Related tests:

TSH; Free T3 or Total T3; Thyroid Panel; Thyroid Antibodies; Calcitonin

Why Get Tested?

To help evaluate thyroid gland function; to help diagnose thyroid disease; to screen for hypothyroidism in newborns; to monitor effectiveness of treatment

When to Get Tested?

When you have signs and symptoms of thyroid disease, usually after an abnormal result on a TSH test; commonly performed as a screening test on newborns soon after birth; when you are being treated for a thyroid disorder

Sample Required?

A blood sample drawn from a vein in your arm or from pricking the heel of an infant

Test Preparation Needed?

None needed; however, certain medications can interfere with the free T4 test, so tell your healthcare provider about any drugs that you are taking. If you take thyroid hormone as treatment for thyroid disease, it is recommended that your blood sample be drawn before you take your dose for that day.

How is it used?

Free thyroxine (free T4) tests are used to help evaluate thyroid function and diagnose thyroid diseases, including hyperthyroidism and hypothyroidism, usually after discovering that the thyroid stimulating hormone (TSH) level is abnormal.

T4 and another hormone called triiodothyronine (T3) are produced by the thyroid gland. They help control the rate at which the body uses energy and are regulated by a feedback system. TSH stimulates the production and release of T4 (primarily) and T3 from the thyroid gland.

Most of the T4 and T3 circulates in the blood bound to protein, while a small percentage is free (not bound). Blood tests can measure total T4, free T4, total T3, or free T3. The total T4 test has been used for many years, but it can be affected by the amount of protein available in the blood to bind to the hormone. Free T4 is not affected by protein levels and is the active form of thyroxine. The free T4 test is thought by many to be a more accurate reflection of thyroid hormone function and, in most cases, its use has replaced that of the total T4 test.

A free T4 test may be used along with or following a TSH test and sometimes with a free T3 test to:

  • Help detect too much or too little thyroid hormone (hyperthyroidism and hypothyroidism) and diagnose the cause
  • Distinguish between different thyroid disorders
  • Help diagnose pituitary disorders
  • Aid in the diagnosis of female infertility
  • Monitor the effectiveness of treatment in a person with known thyroid disorder
  • Monitor people with pituitary disease, to make sure that the thyroid is still working, and to monitor thyroid hormone treatment if it is not
  • Monitor individuals with thyroid cancer, in which the tumors respond to TSH. TSH and T4 levels will be regularly checked to make sure that enough thyroid hormone is being given to keep TSH low without making T4 too high.
  • In the United States, newborns are commonly screened for T4 levels as well as TSH concentrations to check for congenital hypothyroidism, which can cause mental retardation if left untreated.

Free T4 along with TSH may sometimes be used to screen for thyroid disorders, but expert opinions vary on who can benefit from screening and at what age to begin.

If a health practitioner suspects that someone may have an autoimmune-related thyroid condition, then Thyroid Antibodies may be ordered along with a free T4 test.

When is it ordered?

A free T4 test may be ordered when a person has symptoms of hyperthyroidism or hypothyroidism, particularly if the TSH test is out of range.

Signs and symptoms of hyperthyroidism may include:

  • Increased heart rate
  • Anxiety
  • Weight loss
  • Difficulty sleeping
  • Tremors in the hands
  • Weakness
  • Diarrhea (sometimes)
  • Light sensitivity, visual disturbances
  • The eyes may be affected: puffiness around the eyes, dryness, irritation, and, in some cases, bulging of the eyes.

Symptoms of hypothyroidism may include:

  • Weight gain
  • Dry skin
  • Constipation
  • Cold intolerance
  • Puffy skin
  • Hair loss
  • Fatigue
  • Menstrual irregularity in women
  • Enlarged thyroid gland (goiter)

Free T4 testing may be ordered along with other thyroid tests on a regular basis when a person is undergoing treatment for a thyroid disorder.

In pregnant women with thyroid disorders, the health practitioner is likely to order thyroid testing early and late in the pregnancy and for a time period following delivery to monitor the mother and baby.

Thyroid hormone screening is commonly performed on newborns in the United States as part of newborn screening programs.

What does the test result mean?

In general, high free T4 results may indicate an overactive thyroid gland (hyperthyroidism), and low free T4 results may indicate an underactive thyroid gland (hypothyroidism). The test results alone are not diagnostic but will prompt the health practitioner to perform additional testing to investigate the cause of the excess or deficiency.

Both decreased and increased free T4 results are associated with a variety of temporary and chronic thyroid conditions. Low free T4 results in conjunction with a low TSH level or high free T4 results along with a high TSH may indicate a pituitary gland condition.

The following table summarizes some examples of typical test results and their potential meaning.

TSH Free T4 free or Total T3 probable Interpretation
High Normal Normal Mild (subclinical) hypothyroidism
High Low Low or normal Hypothyroidism
Low Normal Normal Mild (subclinical) hyperthyroidism
Low High or normal High or normal Hyperthyroidism
Low Low or normal Low or normal Non-thyroidal illness; rare pituitary (secondary) hypothyroidism
Normal High High Thyroid hormone resistance syndrome (a mutation in the thyroid hormone receptor decreases thyroid hormone function)

When used for monitoring treatment for thyroid or pituitary disorders, results of thyroid tests will inform the health practitioner whether treatment is effective and/or whether an adjustment to dose is necessary. For example, in people with hyperthyroidism, free T4, free T3, and TSH are regularly checked while they are on anti-thyroid drugs to assure that the drugs are working and to decrease doses if thyroid hormone levels get too low. In people with hypothyroidism, TSH and free T4 are regularly checked to assure that the right dose of thyroid hormone is being given to make TSH normal.

Is there anything else I should know?

It is generally recommended that thyroid testing be avoided in hospitalized patients or deferred until after a person has recovered from an acute illness, as thyroid hormone levels may be affected the stress of an illness.

It is important to note that thyroid tests are a “snapshot” of what is occurring within a dynamic system. An individual person’s results may vary and may be affected by:

  • Increases, decreases, and changes (inherited or acquired) in the proteins that bind T4 and T3
  • Pregnancy
  • Estrogen and other drugs
  • Liver disease
  • Systemic illness
  • Resistance to thyroid hormones

Many medications–including estrogen, certain types of birth control pills, and large doses of aspirin–can affect total T4 test results and their use should be discussed with the health practitioner prior to testing. In general, free T4 levels are not affected by these medications.

What is being tested?

Thyroxine (T4) is one of two major hormones produced by the thyroid gland, a small butterfly-shaped organ that lies flat across the windpipe at the base of the throat. The other major thyroid hormone is called triiodothyronine (T3) and together they help control the rate at which the body uses energy. Almost all of the T4 (and T3) found in the blood is bound to protein. The rest is free (unbound) and is the biologically active form of the hormone. This test measures the amount of free T4 in the blood.

T4 production is regulated by a feedback system. When the level of T4 in the bloodstream decreases, the hypothalamus releases thyrotropin releasing hormone, which stimulates the pituitary gland to produce and release thyroid-stimulating hormone (TSH). TSH then stimulates the thyroid gland to make and/or release more T4. As the blood concentration of T4 increases, TSH release is inhibited.

T4 makes up about 90% of thyroid hormones. When the body requires thyroid hormone, the thyroid gland releases stored T4 into circulation. In the blood, T4 is either free (not bound) or bound to protein (primarily bound to thyroxine-binding globulin). The concentration of free T4 is only about 0.1% of that of total T4. T4 is converted into T3 in the liver or other tissues. T3, like T4, is also mostly bound to protein, but it is the free forms of T3 and T4 that are biologically active. Free T3 is 4 to 5 times more active than free T4 in circulation.

If the thyroid gland does not produce sufficient T4, due to thyroid dysfunction or to insufficient TSH, then the affected person experiences symptoms of hypothyroidism such as weight gain, dry skin, cold intolerance, irregular menstruation, and fatigue. Severe untreated hypothyroidism, called myxedema, can lead to heart failure, seizures, and coma. In children, hypothyroidism can stunt growth and delay sexual development.

If the thyroid gland produces too much T4, the rate of the person’s body functions will increase and cause symptoms associated with hyperthyroidism such as increased heart rate, anxiety, weight loss, difficulty sleeping, tremors in the hands, and puffiness around dry, irritated eyes.

The most common causes of thyroid dysfunction are related to autoimmune disorders. Graves disease causes hyperthyroidism and Hashimoto thyroiditis causes hypothyroidism. Both hyperthyroidism and hypothyroidism can also be caused by thyroiditis, thyroid cancer, and excessive or deficient production of TSH. The effect of these conditions on thyroid hormone production can be detected and monitored by measuring the free T4.

How is the sample collected for testing?

A blood sample is obtained from a needle placed in a vein in the arm or from pricking the heel of an infant.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed. Certain medications can interfere with the free T4 test, so tell your health practitioner about any drugs that you are taking. If you take thyroid hormone as treatment for thyroid disease, it is recommended that your blood sample be drawn before you take your dose for that day.

  1. How does pregnancy affect thyroid hormone levels?Pregnancy can increase free T4 levels, although this does not mean that thyroid disease exists. For more information, see the Thyroid Foundation of America’s web page Thyroid Problems During and After Pregnancy – Are You At Risk?
  2. What is FTI?FTI stands for the Free Thyroxine Index and it is an estimation of the free T4 concentration. It is sometimes referred to as T7. It is a calculated value determined from the total T4 test and some estimation of the level of thyroid hormone binding proteins. The original test for estimating the level of binding proteins was called the T3-uptake test and later versions were called T-uptake methods. These are rarely used now that there are methods available to measure free T4 and T3 directly.
  3. Are there things that I can do to raise or lower my free T4 level?In general, free T4 does not respond to lifestyle changes. What is important is that the thyroid gland is producing adequate amounts of free T4 and the body’s feedback mechanism is responding appropriately. For those who do not produce enough free T4, thyroid hormone replacement medication can be given.


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