Thyroid antibodies: TPO, TgAb and TRAb/TSI

What are thyroid antibodies?

Antibodies are proteins the immune system produces to target specific substances. In autoimmune thyroid disease, the immune system mistakenly produces antibodies against parts of the thyroid itself - its enzymes, proteins, or receptors. Measuring these in a blood test can help identify whether the immune system is involved in someone's thyroid condition.

TPO antibodies - the Hashimoto's marker

TPO antibodies (anti-thyroid peroxidase antibodies) target thyroid peroxidase, an enzyme the thyroid uses to make T4 and T3. They are the most commonly tested thyroid antibody.

Elevated TPO antibodies are the hallmark of Hashimoto's thyroiditis and are found in the vast majority of people with this condition. They are also raised in the majority of people with Graves' disease - roughly two-thirds to three-quarters.

TPO antibodies are typically measured when:

• Hypothyroidism is diagnosed, to check if it is autoimmune in origin
• TSH is mildly raised and the cause is unclear
• Thyroid symptoms are present but TSH is normal

A raised TPO result does not necessarily mean thyroid function is abnormal now. Many people with elevated TPO antibodies have normal TSH and free T4 for years. However, it does indicate that the autoimmune process is active, which is a reason to have regular monitoring. The numerical level of TPO antibodies does not reliably predict how quickly or severely thyroid function will change.

TgAb - thyroglobulin antibodies

Thyroglobulin antibodies (anti-Tg, or TgAb) target thyroglobulin, a protein made by the thyroid. They can be raised in Hashimoto's thyroiditis and occasionally in other thyroid conditions.

TgAb are not usually part of a routine thyroid panel. Their main clinical use is in thyroid cancer follow-up: after a total thyroidectomy, thyroglobulin levels are used to monitor for any return of cancer cells. However, TgAb can interfere with the thyroglobulin assay, making results unreliable - so they are measured alongside thyroglobulin in cancer surveillance specifically.

TRAb and TSI - the Graves' markers

TRAb (TSH receptor antibodies) are antibodies that bind to the TSH receptor on thyroid cells. In Graves' disease, these antibodies do not just bind - they actively switch the receptor on, telling the thyroid to keep producing hormone regardless of the feedback signal from the pituitary. This is what drives the sustained overactivity of Graves', for as long as the antibodies are present.

Measuring TRAb is the most specific blood test for Graves' disease. A positive result, in the context of hyperthyroidism, strongly supports the diagnosis. TRAb levels often fall during treatment and may be used to gauge whether remission is likely.

TRAb also matter in pregnancy: because they can cross the placenta and affect the baby's thyroid, women with current or past Graves' disease are usually offered TRAb testing during pregnancy, so both mother and baby can be monitored. This applies even if your own thyroid is now well controlled, has been removed, or was treated with radioactive iodine.

Some laboratories report this as TSI (thyroid-stimulating immunoglobulins) - these terms refer to the same underlying immune activity. Your doctor will interpret whichever measure your laboratory uses.

What a positive antibody result does and does not mean

A positive antibody result is a marker of immune activity - it is not, on its own, a diagnosis of a condition or a prediction of how your thyroid function will behave. To understand what a result means in your situation:

• It needs to be read alongside TSH, free T4, and any symptoms you are experiencing
• The specific antibody matters - TPO and TgAb point in a different direction from TRAb
• Only a clinician who knows your full picture can interpret it for you

If you have a positive antibody result and want to understand it better, note down your questions and bring them to your next appointment. The questions tool can help you prepare.

Questions worth raising with your clinician

• Which antibody was tested and what does a positive result mean for my monitoring?
• If my TPO antibodies are raised but my thyroid function is normal, how often should I be checked?
• What would a change in my TRAb levels tell us about my treatment?