According to the American Thyroid Association, around 20 million Americans have thyroid disease, but up to 60% of them may not be aware of their condition. Symptoms of poor thyroid function, such as fatigue and weight gain, are common and may not be attributed to a thyroid condition until thyroid function tests become abnormal. (Source) 

Thyroid function tests assess how well your thyroid gland is working and help determine if you have a thyroid disease. In this edition, we’ll explore the signs and symptoms of thyroid diseases and what tests are offered to diagnose those diseases. 

What Is the Thyroid Gland?

The thyroid gland is a butterfly-shaped organ located at the front of the neck. The thyroid is responsible for producing thyroid hormones, which circulate in the bloodstream to affect target organs. Thyroid hormones help control the body’s metabolism (the breakdown or build-up of various substances), affect mood, and are important for growth, as well as for fertility and menstruation in women. (Source)

How Are Thyroid Hormones Made?

Production of thyroid hormones involves several steps, starting in the hypothalamus, one of the brain’s control centers. Thyrotropin releasing hormone (TRH) produced by the hypothalamus travels to the adjacent pituitary gland, stimulating it to produce thyroid-stimulating hormone (TSH, also known as thyrotropin). Finally, TSH is released into the bloodstream, travels to the thyroid gland, and prompts it to create thyroid hormones. 

In the thyroid gland, a precursor of thyroid hormones called thyroglobulin reacts with iodine to create two thyroid hormones: triiodothyronine (T3) and thyroxine (T4). Even though T3 is the more biologically active hormone, not very much is made by the thyroid. Instead, the thyroid produces larger quantities of T4, and it is converted into T3 elsewhere in the body. (Source) 

How Are Thyroid Hormones Regulated?

The hypothalamus, pituitary gland, and thyroid gland work together to make up a feedback loop known as the hypothalamic-pituitary-thyroid (HPT) axis. In a feedback loop, the components of the loop try to maintain a normal physiological balance in the body by monitoring and responding to what the other components are doing.

When T3 and T4 levels in the blood are too high, production of TRH by the hypothalamus and TSH by the pituitary gland is suppressed until T3 and T4 levels return to normal levels. Conversely, when T3 and T4 levels are too low, TRH and TSH production will be increased in an effort to bring T3 and T4 up to normal levels. (Source)

Thyroid Hormone Misregulation 

Abnormalities in thyroid hormone production, regulation, or function may lead to the development of either hyperthyroidism or, more commonly, hypothyroidism. These conditions may be primary, in which they are caused by a problem with the thyroid gland itself, or secondary, in which they are caused by a problem elsewhere, such as in the hypothalamus or pituitary gland.

Both hyperthyroidism and hypothyroidism can also be subclinical, in which they cause few if any noticeable symptoms and blood tests are only slightly abnormal.  

Hyperthyroidism

Hyperthyroidism occurs when there are excess thyroid hormones in the body. This can cause symptoms such as: 

• weight loss
• increased appetite
• weakness
• heat intolerance
• anxiety
• depression
• fatigue

Hypothyroidism 

In hypothyroidism, there are decreased levels of thyroid hormones circulating in the body. Symptoms of hypothyroidism include but are not limited to:

• weight gain
• decreased appetite
• hair loss
• constipation
• cold intolerance
• depression
• fatigue

(Source, Source)

Should I Get My Thyroid Tested?

Symptoms of thyroid dysfunction such as changes in mood, weight, fatigue, and hair loss are non-specific and may be attributed to other causes. The only way to confirm a diagnosis of thyroid disease is by having the appropriate thyroid function tests. (Source)

It is possible for some medications to affect thyroid hormone levels, and these need to be taken into account when interpreting laboratory test results. Your health care provider should review your medication history with you before ordering tests. (Source, Source)

What Tests Should I Get to Assess My Thyroid Function?

Thyroid Hormone Blood Tests

Blood tests can measure the levels of several different thyroid hormones. There are currently no fasting requirements for tests to assess thyroid function, but timing is important because hormone levels fluctuate throughout the day. (Source, Source)  

Thyroid Stimulating Hormone (TSH)

Checking TSH levels is recommended as the initial test for thyroid dysfunction, as it is the most sensitive and specific indicator of thyroid function. (Source) 

Primary Thyroid Disorder

• High TSH levels along with decreased thyroid hormone (T3 and T4) levels may indicate primary hypothyroidism — an underactive thyroid. 
• Decreased TSH levels and increased thyroid hormone levels indicate primary hyperthyroidism — an overactive thyroid. 

Subclinical Primary Thyroid Disorder

Primary hypothyroidism and hyperthyroidism may be considered subclinical if T3 and T4 hormone levels are normal, there are no symptoms, and only the TSH level is abnormal. 

• Subclinical hypothyroidism is characterized by increased TSH levels, because the pituitary gland is trying to stimulate the thyroid to produce more T3 and T4. (Source)
• Subclinical hyperthyroidism, on the other hand, is characterized by decreased TSH levels, as the HPT axis is working to lower the amounts of T3 and T4 being produced. (Source)

Secondary Thyroid Disorder

• In secondary hypothyroidism, T3 and T4 levels are decreased because TSH levels are lower than normal. (Source)
• In secondary hyperthyroidism, both TSH and thyroid hormone levels are elevated. (Source)

Free Thyroxine (Free T4/FT4)

Your primary care provider may order a FT4 test concurrently with a TSH test, or after a TSH test if abnormalities are found. (Source) 

Most T4 in the blood is attached to proteins, primarily thyroxine-binding globulin (TBG). This protein binding allows it to be transported around the body, but also renders it inactive. This form of the hormone is known as bound T4. 

Free T4, or FT4, is T4 that is not bound to proteins. Free T4 can be converted to T3, the more biologically active form of the hormone, and FT4 is the most clinically relevant measure of T4. (Source) 

When FT4 and TSH levels are both abnormal, it is likely the problem is with the thyroid gland itself. In primary hyperthyroidism, FT4 levels are high and TSH levels are low. In primary hypothyroidism, FT4 levels are low and TSH levels are high. (Source) 

Free Triiodothyronine (Free T3/FT3)

Like T4, T3 is either bound or free. Because T3 has a greater affinity than T4 to receptors in tissues around the body, it has a more marked biological effect. Bound T3 must be converted to free T3, or FT3, before it can enter cells. 

In primary hyperthyroidism, FT3 levels are high and TSH levels are low. And in primary hypothyroidism, FT3 levels are low and TSH levels are high. (Source) 

Reverse Triiodothyronine (RT3)

Reverse T3, or RT3, is the inactive form of T3, and to decrease thyroid hormone levels in circulation T4 may be converted to RT3 instead of T3. The evidence suggesting a relationship between RT3 levels and thyroid diseases is sparse and there is limited support for the clinical use of RT3 tests. (Source)

However, it has been shown that high RT3 levels may indicate excess thyroid hormone function and, conversely, low RT3 levels may be found in those with hypothyroidism. (Source)

Triiodothyronine Resin Uptake (T3RU) 

Abnormal T4 levels can indicate a problem with the thyroid, but there can also be a problem with TBG, the main T4-binding protein. When the TBG concentration is too high or too low, or if TBG is not binding T4 properly, T4 levels will be abnormal even though the thyroid gland is functioning properly.

The T3RU test measures TBG’s binding capacity for T4 from your blood sample. T3RU test values should be evaluated in conjunction with T4 test results for accuracy. High T4 and TBG levels result in a low T3RU value, whereas low T4 and TBG levels result in a high T3RU value. (Source)

Thyroid Antibody Blood Tests 

Thyroid autoantibodies are antibodies that attack thyroid tissue and therefore alter thyroid levels. In thyroid antibody blood tests, thyroid autoantibodies are measured to detect the presence of autoimmune thyroid disease (AITD). The two most common AITDs are Hashimoto's thyroiditis, which causes hypothyroidism, and Graves’ disease, which causes hyperthyroidism. (Source, Source) 

Anti-Thyroid Peroxidase (TPO) Antibodies

Thyroid peroxidase (TPO) is an enzyme that drives two important steps in the production of T3 and T4 in the thyroid gland. Anti-TPO antibodies are toxic to thyroid cells, decreasing TPO activity and thyroid hormone synthesis. In Hashimoto’s thyroiditis, anti-TPO antibodies are present, thyroid hormone levels are decreased, and TSH levels are increased. These antibodies may also be found in patients with Graves’ disease, but their role is less understood. (Source, Source)

Anti-Thyroglobulin (Tg) Antibodies

Thyroglobulin (Tg) is a protein that is modified in the thyroid gland to create T3 and T4. Anti-Tg antibodies, along with anti-TPO antibodies, are often found in patients with Hashimoto’s thyroiditis. Both anti-Tg antibodies and anti-TPO antibodies may be present in patients with Graves’ disease as well, but this is less common. (Source)

Anti-TSH Receptor (TSHR) Antibodies

The TSH receptor (TSHR) is a docking site for TSH on the surface of thyroid gland cells, which allows TSH to exert its effects. 

There are three different kinds of anti-TSHR antibodies (TRAbs):

• TSHR stimulating antibodies (TSAbs) bind to the TSHR and stimulate excess thyroid hormone production, making them a clear marker of Graves’ disease. 
• TSHR blocking antibodies (TBAbs) result in decreased thyroid hormone production, implicating them in development in Hashimoto’s thyroiditis.
• TSHR neutral antibodies are less common and their effects, if any, are not clear yet. 

(Source, Source, Source)

Radioactive Iodine Uptake (RAIU) Test 

If blood test results appear abnormal, an RAIU test may be performed next. The RAIU measures the ability of the thyroid to take up iodine, which is critical for the synthesis of T3 and T4. For this test, the patient is given iodine combined with a radioactive marker, and a scanner tracks the movement of the iodine into the thyroid gland.

Increased RAIU is often associated with hyperthyroidism, Graves’ disease, early-stage Hashimoto’s thyroiditis, or iodine insufficiency. Alternatively, decreased RAIU is associated with hypothyroidism and excess iodine intake. (Source, Source)

What Is a Full Panel Thyroid Test?

The individual tests included in a full panel thyroid test varies, but consists of a combination of hormone blood tests, such as TSH, FT3, FT4, RT3, and T3RU tests, and may include antibody blood tests, such as an anti-TPO antibody, anti-Tg antibody, and anti-TSHR antibody tests. (Source, Source) 

The Bottom Line on Tests to Assess Thyroid Function

The thyroid gland and the hormones it produces play a vital role in regulating metabolism, mood, and growth. Because thyroid hormones affect so many physiological processes, thyroid dysfunction can’t be diagnosed based on symptoms alone. To detect a possible thyroid disease, your thyroid function may be assessed through blood tests, antibody tests, an uptake test, or all of the above.