Thyroid antibodies explained

Reading and interpreting thyroid blood tests results can often be a challenge. So, it's no surprise we frequently hear from patients who would like assistance with this. One particular area of interest is thyroid antibody testing: Whether and how often antibodies should be tested and what their presence means? We take a look at these frequently asked questions.

What are thyroid antibodies and what do they indicate?

Antibodies are proteins that form in the blood in response to invasion by foreign proteins (antigens). They help protect us from viruses and bacteria. Thyroid antibodies develop when a person's immune system mistakenly attacks the thyroid cells and tissues. This leads to inflammation, tissue damage or disrupted thyroid function. These antibodies cause autoimmune thyroid disorders, such as Graves' disease and Hashimoto's thyroiditis.

If the initial thyroid test results show signs of a thyroid problem, and if there is a suspicion of autoimmune thyroid disease, one or more thyroid antibody tests may be ordered. Antibody tests are used to confirm the diagnosis of autoimmune thyroid diseases. Some people will test positive for more than one type of thyroid antibody.

In people with subclinical thyroid disease, the presence of antibodies can indicate the person may go on to develop full-blown thyroid disease in the future, but that treatment is not yet required. Positive antibodies can also be present in people without thyroid disease.

Antibodies

What do they indicate?

Thyroid peroxidase antibodies (TPOAb)

Raised in Hashimoto's thyroiditis (or autoimmune thyroiditis) and sometimes raised in Graves' disease

Thyroglobulin antibodies (Tg Ab) – antibodies directed against the thyroglobulin (a protein present in the thyroid gland), from which thyroid hormones are produced

May be measured as part of the monitoring of people previously treated for thyroid cancer. Also sometimes raised in Hashimoto's thyroiditis

Thyroid stimulating hormone receptor antibodies (TSHR Ab, also known as TRAb). TRAb is potentially stimulatory and blocking to the thyroid gland.

Raised in Graves' disease

Thyroid Stimulating Immunoglobulin (TSI) antibody specific to Graves' disease. It is a stimulatory antibody and the one that causes an overactive thyroid gland.

May be raised in Graves' disease. This is not routinely tested and used mainly as a research tool.

What is the Thyroid Peroxidase Antibodies (TPOAb) test used for?

TPO antibodies may be checked in patients with a high TSH, to help establish the underlying cause. If the TPO antibodies are positive, it means the cause of hypothyroidism is an autoimmune disease (e.g. Hashimoto's thyroiditis). If they are negative, it means they may not have a thyroid disorder and that the high TSH may resolve spontaneously, or there is an underlying thyroid disorder caused by another factor (e.g. following a viral infection or due to prescribed medication).

It is normally only necessary to measure TPOAb once when trying to establish the cause of the thyroid disorder. TPO antibodies are found in more than 90% of people with autoimmune hypothyroidism and also in about 10% of people without a thyroid disorder where they may be 'markers' of autoimmunity. This means they may be more likely to develop autoimmune disease in the future.

What are thyroid stimulating antibodies (TRAb) and why is it tested?

In Graves' disease, the thyroid stimulating antibodies (TRAb) mimic the thyroid stimulating hormone (TSH) secreted by the pituitary gland. This causes the thyroid to continue to produce thyroid hormones, despite the pituitary trying to switch off the thyroid by stopping production of TSH. The presence of TRAb suggests a person has Graves' disease. Approximately 95% of patients with Graves' disease will have raised TRAb and 70% will also have raised TPOAb. The severity of Graves' disease is often reflected in the levels of TRAb present. For example, where the TRAb levels are very high, the patient is less likely to achieve long-term remission following a course of treatment with antithyroid drugs.

It is sometimes possible for antibodies to be negative, but for a scan to confirm a Graves' disease diagnosis.

What is thyroglobulin and why are thyroglobulin antibodies tested?

Thyroglobulin (Tg) is produced by thyroid cells: both noncancerous (benign) and cancerous cells. It plays a key role in helping the body create, store and release thyroid hormones. After successful thyroid surgery and radioactive iodine ablation for thyroid cancer, thyroglobulin should not be detectable in the blood. The presence of detectable thyroglobulin, particularly a rising thyroglobulin level, may give an early warning of a recurrence of the cancer. Thyroglobulin antibodies are directed against the thyroglobulin molecule and are found in approximately 10% of the general population; they can be raised in people with Hashimoto's thyroiditis.

Where they are present it can affect the accuracy of the measurement of thyroglobulin and so additional means need to be used to monitor people who have had treatments for thyroid cancer. Thyroglobulin antibodies generally do not add anything to TPO antibody results in the assessment of people with a raised TSH.

Is it necessary to repeat testing for thyroid antibodies?


It is rarely useful to repeat measurements of TPOAb, as their level does not usually influence the treatment given or the response to treatment. In contrast, measurements of TRAb can be used to guide treatment decisions in Graves' disease (autoimmune thyroid overactivity). For example, relapse of Graves' disease is more likely if antithyroid drugs (ATD) are stopped when TRAb are still raised. Thyroglobulin antibodies are also measured regularly in the follow-up of thyroid cancer, to
ensure the continued accuracy of the thyroglobulin measurement.


Is it possible for thyroid antibodies to go away?

It is possible. In Graves' disease patients, antithyroid medication, radioactive iodine (RAI) and surgery all aim to restore the thyroid function to normal. RAI and surgery destroy or remove the thyroid to 'cure' the overactivity. However, the TRAb, which are the underlying cause of the Graves' disease, may remain in the body for many years after these treatments. Sometimes the TRAb disappear after a course of ATD; however, they may return months or years after stopping ATD,  causing a relapse of Graves' disease.

In patients with autoimmune hypothyroidism (Hashimoto's thyroiditis), TPO antibodies usually remain in the body. Levels may reduce over time, but hardly ever normalise completely, even after medication has restored thyroid levels to normal.

If I have autoimmune thyroid disease, am I more likely to develop other autoimmune diseases?


Although someone with an autoimmune thyroid disorder is more likely to develop another  autoimmune condition, such as Addison's disease, pernicious anaemia or coeliac disease, the risk is still very small. It is important, however, that such conditions are considered in patients with  autoimmune thyroid disease if they develop new or nonspecific symptoms.

If I have raised thyroid antibodies, but subclinical thyroid disease, am I more likely to develop full-blown thyroid disease?

Yes, the presence of thyroid antibodies can indicate a person may go on to develop full-blown thyroid disease that will require treatment.

Key points:

• The presence of antibodies is used to confirm the diagnosis of autoimmune thyroid diseases.

• Some people will test positive for more than one type of thyroid antibody.

• It is possible to test positive for thyroid antibodies without having thyroid disease.

• It is rarely useful to repeat measurements of TPOAb as their level does not influence the treatment given.

• Thyroid antibodies often remain in the body even after the thyroid disorder has been successfully treated.

• The presence of antibodies in a person with subclinical (or borderline) thyroid disease can indicate a person may go on to develop full-blown thyroid disease in the future.

This article appeared in BTF News, June 2021 and was written with input from our BTF medical advisors.

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Your guide to thyroid function tests