Which Antibodies Signal Hyperthyroidism?

Graves’ disease, an autoimmune condition, is a common cause of hyperthyroidism in developed countries. In the United States, Graves’ disease accounts for up to 80% of all hyperthyroid cases.

Antibodies are proteins produced by B cells that are meant to neutralize and destroy foreign invaders, such as viruses and bacteria. In Graves’ disease, B cells produce large amounts of antibodies that mistakenly attack the thyroid gland.

Experts are unsure what prompts the immune system to attack the body’s tissues. However, most cases of autoimmune hyperthyroidism begin when B cells produce antibodies that bind to the thyroid-stimulating hormone (TSH) receptors on the thyroid gland.

These antibodies stimulate the TSH receptors, activating them. This, in turn, prompts the thyroid gland to increase thyroid hormone production, causing hyperthyroidism.

The presence of high levels of specific antibodies in the blood tells healthcare professionals that autoimmune hyperthyroidism is a possibility.

The most common and clinically significant types of antibodies associated with hyperthyroidism are the TRAbs. High thyroid-stimulating immunoglobulin (TSI) antibodies, a subtype of TRAbs, are usually high in Graves’ disease.

Other types of thyroid antibodies, such as TPOAbs and thyroglobulin antibodies (TGAbs), may also occur in Graves’ disease. However, these antibodies are also commonly associated with other thyroid conditions, such as autoimmune hypothyroidism or Hashimoto’s thyroiditis. That’s why the presence of TRAbs and TSI antibodies is usually more indicative of hyperthyroidism.

A healthcare professional will usually begin with thyroid function tests.

A TSH test is one of the most common lab tests to check thyroid function. TSH levels within the expected range signal adequate thyroid hormone production. Significantly low levels of TSH indicate overproduction of thyroid hormone, and vice versa.

In hyperthyroidism, TSH levels are lower because the brain is halting its release in response to the overproduction of thyroid hormone. In other words, the body has recognized that there’s no need to stimulate thyroid hormone production because there’s already plenty of it.

Tests for T4 and T3 are also in order. Hyperthyroidism is confirmed when TSH is unusually low and T3 and T4 levels are significantly high.

To determine the cause of hyperthyroidism, your healthcare professional will recommend antibody tests, including the following.

TRAb

When your healthcare professional suspects hyperthyroidism, tests for TRAb include TSI and thyrotropin-binding inhibitory immunoglobulin.

According to a 2021 paper, TSI is highly sensitive (96%) and specific (99%) for Graves’ disease. In other words, high levels of TSI indicate autoimmune hyperthyroidism.

TPOAb

TPOAbs, also known as TPO or anti-TPO antibodies, attack thyroperoxidase, which is an enzyme that helps synthesize and release thyroid hormone.

Anti-TPO is elevated in up to 70% of people with Graves’ disease, according to a 2022 paper. It’s also common in other thyroid diseases, like Hashimoto’s disease.

Anti-TPO is also present in approximately 10% of people with no thyroid condition, so high levels of anti-TPO aren’t enough to make a diagnosis.

TGAb or anti-TG

TGAbs attack thyroglobulin, which is a protein that helps your thyroid produce and release thyroid hormone.

This antibody may be elevated in people with Graves’ disease, but it’s more common in autoimmune hypothyroid disorders, like Hashimoto’s disease.

TGAb is also used to monitor treatment response in people with thyroid cancer.

The same 2022 paper estimates that TGAbs occur in approximately 20% of people with no thyroid condition, so it’s not a diagnostic tool on its own.

Not always. Although irregular TSI levels are a stronger indicator of autoimmune thyroid disease, thyroperoxidase and thyroglobulin antibodies are present in 10% and 20% of healthy adults, respectively.

Conversely, people with autoimmune hyperthyroidism can sometimes test negative for thyroid antibodies. In those cases, doctors use another form of testing, such as thyroid scanning with radioactive iodine uptake testing, to make a diagnosis.

What causes thyroid antibodies to be high?

Thyroid antibodies signal that something has mistakenly triggered your immune system to attack thyroid cells. Experts are unsure what triggers this process, but it’s likely a combination of genetic and environmental risk factors.

The following may increase your chance of developing thyroid antibodies:

• a family history of autoimmune thyroid disease
• a personal history of other autoimmune disease
• chronic stress
• cigarette smoking
• excessive iodine exposure
• postpartum status

Can hyperthyroid antibodies go away?

Yes. Occasionally, some people might see their thyroid antibodies go down after treatment. But they can also remain steady, increase, or recur over time. Healthcare professionals monitor your condition status and response to therapy by periodically testing your antibodies.

What are the standard ranges for thyroid antibodies?

Different laboratories and test manufacturers may set different ranges. The prescribing doctor will explain what your results mean.

Test results usually also include the lab’s range, so you can have that reference. In general, experts consider these ranges non-indicative of thyroid disease:

• TSI: below 1.3 or 130%
• anti-TPO: below 9 international units per milliliter (IU/mL), but they range widely from lab to lab
• TGAb: wide range variation depending on the testing method, but a negative TGAb test usually means no autoimmune thyroid disease
  

Having hyperthyroidism, or an overactive thyroid, means your body produces a significantly higher amount of thyroid hormone. Graves’ disease, an autoimmune condition, is the most common cause of hyperthyroidism in the United States. The presence of specific antibodies usually signals Graves’ disease.

An elevated TRAb level, including TSI and anti-TPO antibodies, is usually the clearest sign of autoimmune hyperthyroidism.