Tetraiodothyronine/T4 (Total Thyroxine)
T4 is a thyroid hormone, and too much or too little of it can indicate an issue with the thyroid. A T4 (thyroxine) test is a blood test that helps diagnose thyroid conditions.
Thyroxine (T4) plays an important role in the hypothalamic-pituitary system of thyroid regulation and has an influence on general metabolism. T4 results from the coupling of two molecules of 3,5-diiodotyrosine, is bound to thyroglobulin and remains in the cells of the thyroid follicles, from where it is excreted under the action of TSH.
Other names when referring to a T4 test may include: free thyroxine, total T4 concentration, thyroxine screen, free T4 concentration, free T4 index (FTI).
The thyroid is a small, butterfly-shaped gland located at the front of the lower neck, above the clavicle. It's a part of the endocrine system and it makes hormones that control the way the body uses energy. These hormones affect nearly every organ in the body and control many of the body's most important functions. For example, they affect the breathing, heart rate, weight, digestion, and mood. In children, thyroid hormones affect growth, too. The thyroid gland makes and releases thyroid hormones in the blood, which then travel to the organs to exert their effect.
There are two forms of T4 in the blood:
- Free T4 is the active form of thyroxine hormone that enters the body tissues where it is needed;
- Bound T4 is thyroxine that attaches or binds to certain proteins which prevent it from entering the body tissues. It stays in the bloodstream as a "backup supply" until the tissues need it.
Together, T4 and T3 play vital roles in regulating various bodily functions, such as:
- Metabolic rate (the rate at which the body transforms the food that is eaten into energy);
- Heart and digestive functions;
- Muscle control;
- Brain development;
- Bone maintenance.
- A free T4 test measures the amount of free T4 in the blood. This form "freely" enters the body's tissues where it's needed. Medical experts believe this test is more accurate than a total T4 test, so it's used more often;
- A total T4 test measures free and bound T4 together; Bound T4 attaches to proteins, which prevents it from entering the body's tissues.
A TSH test is the best way to initially assessing the thyroid function. In fact, T4 tests more accurately reflect thyroid function, when combined with a TSH test. Measuring T4 levels might not be necessary in all thyroid conditions.
Recommendations for T4 determination:
- diagnosis of hyper- and hypothyroidism (primary or secondary);
- monitoring of TSH suppressive treatment.
Patient preparation: fasting (without food); if the patient is on treatment with hypolipidemic drugs containing thyroxine, blood sampling for T4 determination will be done 4-6 weeks after its discontinuation. Specimen collected: venous blood.
Why is it a T4 (thyroxine) test needed?
Healthcare providers may use T4 tests to assess how well the thyroid is working. The provider may order a T4 test (in addition to a TSH test) for any of the following reasons:
- To follow up on an abnormal thyroid-stimulating hormone (TSH) test result;
- To diagnose hyperthyroidism (overactive thyroid) or hypothyroidism (underactive thyroid);
- To monitor T4 levels if taking thyroid hormone replacement therapy (medication);
- To screen for an underactive thyroid in newborns;
- To evaluate other conditions, such as goiter, thyroid nodules and issues with the pituitary gland or hypothalamus;
- To evaluate for low thyroid hormone levels from a pituitary cause (central hypothyroidism).
Again, providers more commonly order free T4 tests than total T4 tests. In certain situations, such as pregnancy, a total T4 test might be necessary rather than a free T4 test.
T4 (Total Thyroxine) Reference Values:
- are based on age:
Age: Value (nmol/L): Value (µg/dL):
0 - 6 days 64.9 - 239 5.04 - 18.5
6 days - 3 months 69.6 - 219 5.41 - 17
3 - 12 months 73 - 206 5.67 - 16
1 - 6 years 76.6 - 189 5.95 - 14.7
6 - 11 years 77.1 - 178 5.99 - 13.8
11 - 20 years 76.1 - 170 5.91 - 13.2
> 20 years 66.0 - 181 5.13 - 14.1
In pregnancy, T4 level increases by 40-60%, starting with weeks 11-12, due to the increase in TGB:
1st trimester: 94.4 - 191 nmol/L (7.33 - 14.8 µg/dL);
2nd trimester: 102 - 208 nmol/L (7.93 - 16.1 µg/dL);
3rd trimester: 89.5 - 202 nmol/L (6.95 - 15.7 µg/dL).
Detection limit - 5.40 nmol/L (0.42 µg/dL).
Clinical alert values - low level: <26 nmol/L (possibility of myxedema coma); high level: >258 nmol/L (possibility of "Thyroid storm").
Limitations and interferences
In the first 2 months of life, T4 shows values much higher than in normal adults.
Elevated T4 values can also be found in dysalbuminemic familial hyperthyroxinemia - albumins bind T4 more avidly than normal, but not T3, causing laboratory changes similar to those in thyrotoxicosis, but the patients are not clinically thyrotoxic.
Normal T4 values can be found in hyperthyroid patients who present T3 thyrotoxicosis or artificial hyperthyroidism due to T3.
What are normal free T4 levels?
Normal levels of free T4 vary based on the age. In general, normal ranges of free T4 for healthy people include:
- Children up to 5 years old: 0.8 - 2.8 nanograms per deciliter (ng/dL);
- Children 6 to 15 years old: 0.8 - 2.1 ng/dL;
- Male adolescents 16 to 17 years old: 0.8 - 2.8 ng/dL;
- Female adolescents 16 to 17 years old: 0.8 - 1.5 ng/dL;
- Adults over 18 years old: 0.9 - 1.7 ng/dL.
Normal value ranges for free T4 may vary slightly among different laboratories. One should check the lab report's reference range on the lab results. If there are questions about the results, the patient should ask the healthcare provider.
What happens when T4 (thyroxine) levels are too high?
If the patient has higher-than-normal T4 or free T4 levels, it could indicate thyrotoxicosis. This can result from several situations and conditions, including hyperthyroidism (overactive thyroid), thyroid inflammation (thyroiditis) and taking excessive amounts of thyroid medication.
Thyrotoxicosis speeds up the metabolism, which can be dangerous to the patient's health. Symptoms of thyrotoxicosis include:
- Unexplained weight loss;
- Increased bowel movements;
- Rapid or irregular heartbeat (arrhythmia).
If one is experiencing symtoms of thyrotoxicosis, it's important to contact the healthcare provider.
Other conditions that could cause elevated total T4 levels with normal free T4 levels include pregnancy and estrogen-containing birth control pills. This is because estrogen levels are high in those two scenarios. Estrogen increases the proteins bound to T4 and causes the total T4 (which is free T4+ binding proteins) to be high.
What happens when T4 (thyroxine) levels are too low?
If a patient has lower-than-normal T4 levels, it usually indicates hypothyroidism (underactive thyroid). Hypothyroidism has several causes, including certain autoimmune diseases, poor iodine intake in the diet and the use of certain medications.
Hypothyroidism slows down the metabolism. Symptoms include:
- Fatigue;
- Intolerance of cold temperatures;
- Low heart rate;
- Weight gain.
If symptoms of hypothyroidism are experienced, it's important to talk to the healthcare provider.
If the T4 test results are irregular, the provider may order more thyroid tests to help make a diagnosis. These tests may potentially include:
- T3 (triiodothyronine) test (another thyroid hormone);
- A TSH (thyroid-stimulating hormone) test;
- Tests to diagnose Graves disease, an autoimmune disease that causes hyperthyroidism;
- Tests to diagnose Hashimoto disease, an autoimmune disease that causes hypothyroidism.
How are TSH (thyroid-stimulating hormone) and T4 (thyroxine) levels related?
TSH and T4 are related, since thyroid-stimulating hormone (TSH) triggers the production of thyroxine (T4) and temporarily elevated levels of T4 prevent the release of TSH. TSH and T4 levels directly affect each other.
When one gets their blood tests that check the thyroid function and TSH level, different levels of each hormone can indicate different conditions.
Low TSH and normal T4
Having low TSH levels and normal T4 levels is usually considered subclinical hyperthyroidism. "Subclinical" means the condition doesn't cause any symptoms or symptoms haven't yet started. Studies estimate that subclinical hyperthyroidism affects up to 16% of the population. If the blood test report reveals these results, the healthcare provider will likely continue to monitor the levels to see if they change and result in clinical hyperthyroidism.
Low TSH and high T4
Having low TSH levels and high T4 levels typically indicate hyperthyroidism. This is because excess T4, due to an issue with the thyroid, is preventing the hypothalamus from releasing TSH.
Low TSH and low T4
Having low TSH and low T4 levels may indicate that one is having an issue with the pituitary gland, such as large pituitary adenoma, that's preventing it from releasing enough TSH to trigger T4 production. This is a less common result combination.
High TSH normal T4
When a patient is having high TSH levels and normal T4 levels, it's usually considered subclinical hypothyroidism (also called mild thyroid failure). This condition occurs in 3% to 8% of the population.
If the blood test report reveals these results, the healthcare provider will likely continue to monitor the levels to see if they change and result in clinical hypothyroidism.
High TSH and low T4
Having high TSH and low T4 levels usually indicates hypothyroidism, an underactive thyroid due to a primary thyroid problem. This is a lack of T4 production due to an issue with the thyroid that's causing the pituitary gland to release excess TSH to try to stimulate the thyroid into making more T4.
High TSH and high T4
Having high TSH and high T4 levels may indicate that the patient has an issue with the pituitary gland that's causing it to release too much TSH, and thus triggering the thyroid to make excess T4. This is an extremely rare result combination.
Patients should know that thyroid conditions are fairly common, especially hypothyroidism, and are treatable. The healthcare provider will let the patient know if there is a need to undergo further tests to determine the cause of the abnormal T4 level. Patients should ask more questions if there are, to their healthcare provider.
What a T4 test is used for? Summary
A T4 is usually used with other thyroid tests to help diagnose and monitor thyroid disease and to gather more information about other conditions that may affect the thyroid. It may be used to:
- Diagnose:
- Hypothyroidism;
- Hyperthyroidism.
- Help learn more about:
- Other thyroid conditions, such as if a patient has thyroid nodules (growth on the thyroid that aren't cancer) or a goiter (an enlarged thyroid that may make the neck look swollen). Sometimes these conditions can cause high T4 levels;
- Disorders of the pituitary gland; abnormal T4 levels are usually caused by thyroid problems, but sometimes they are a sign of a pituitary problem that causes too much or too little TSH;
- Disorders of the hypothalamus, an area of the brain that controls the pituitary gland and other body functions.
- Check a newborn for congenital hypothyroidism, which is hypothyroidism that is present at birth;
- Check the T4 levels, if the patient is taking thyroid hormone medicine to treat hypothyroidism.
In certain cases, a T4 test may be done as part of a group of thyroid tests called a thyroid panel.
Why does a patient need a thyroxine (T4) test? Summary
A patient may need a T4 test if:
- the patient had abnormal results on a TSH test;
- the patient has symptoms of hypothyroidism. Not having enough thyroid hormone slows down the body functions. The symptoms can vary from person to person and may include:
- Fatigue
- Weight gain
- Being very sensitive to cold
- Joint and muscle pain
- Dry skin
- Dry, thinning hair
- Heavy or irregular menstrual periods
- Fertility problems in women
- Slow heart rate
- Depression
- Constipation
- the patient has symptoms of hyperthyroidism. Having too much thyroid hormone speeds up the body's functions. The symptoms can vary from person to person and may include:
- Weight loss, even though the patient may be eating more than usual
- Rapid or irregular heartbeat
- Feeling nervous or irritable
- Trouble sleeping
- Fatigue
- Shaky hands, muscle weakness
- Sweating or being very sensitive to heat
- Frequent bowel movements (pooping a lot) or diarrhea
- Goiter
- a member of the patient's family has had thyroid disease. Thyroid disease tends to run in families;
- the patient is taking thyroid hormone medicine for hypothyroidism. A T4 test may be used to check how well the treatment is working;
- the patient has symptoms that could be caused by another thyroid condition or a problem with the pituitary gland.
What do the results mean?
If the patient had a free T4 test, the test results may be reported as "free T4". If the patient had a total T4 test, the results may be reported as "free T4 index (FTI)". FTI is the amount of free T4 in the blood, based on a calculation using the total T4 test results.
To fully understand the results, the healthcare provider will usually need to compare them with the results of other thyroid tests.
If the T4 results are abnormal, the patient may need more testing to find the cause. But abnormal T4 levels don't always mean that the patient has a severe medical condition.
T4 and pregnancy
Thyroid disease can develop during pregnancy, but it's not common. If this happens, the healthcare provider will treat the patient, if necessary. After the woman gives birth, she would usually have the thyroid checked again.
If a patient had thyroid disease, she should tell her healthcare provider if she is pregnant or if she is thinking about becoming pregnant.
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