Autoantibodies As Potential Immunological Markers
TG and TPO antibodies provide readily available evidence for Graves disease although not specific, their presence in a patient with hyperthyroidism strongly suggests the diagnosis. These antibodies are present in 2030% of cases 57 years before diagnosis . TSAb are not generally measured because present bioassays are laborious. TBII estimation is a commercially available surrogate and is useful in confirming the diagnosis of Graves disease in the absence of clinical evidence such as ophthalmopathy. TSAb or TBII levels have been investigated as predictive markers for the success of antithyroid drug treatment in Graves disease. Although patients with the highest levels tend to relapse the most, the results are insufficiently accurate for clinical use . The most important indication for TSAb assay in Graves disease is in women with known Graves disease during pregnancy to predict the risk of neonatal thyrotoxicosis .
Wilmar M. Wiersinga, in, 2004
What Is The Normal Range For Tpo Antibodies
In general, you will want your TPO antibodies to be as LOW as possible.
That means nonexistent or < 30 U/mL.
The reason for this is simple:
We know that the presence of antibodies indicates potential damage to the thyroid gland.
Getting your antibodies to as close to zero as possible ensures that these antibodies arent floating around in your bloodstream capable of inducing damage.
The standard reference range for thyroid peroxidase antibodies is given as a value less than some number.
This may sound ambiguous, but its just how it is.
In most cases, the normal range is given as less than 60 U/mL or even less than 30 U/mL.
If you pull out your own lab tests and compare, you may find that your reference range is a little bit different and thats okay.
As long as you focus on getting your antibody levels to as close to zero as possible then you are on the right track.
More important than the absolute level of antibodies in your blood is the trend of those antibodies over time.
In other words, what level you started at is less important than the fact that your antibodies are slowly trending down over time.
Combining your antibody level with how you are feeling is also important.
It is possible, though not common, that you may see a mismatch between how you are feeling and your antibody level.
For most people, though, as TPO levels decline you should see an improvement in your low thyroid symptoms.
Each case is different, though, so dont hold this as a standard!
Who Is Most Likely To Develop Hashimotos Disease
Hashimotos disease:
- Is more common in women than men.
- Commonly appears between the ages of 30 and 50.
- Tends to run in families .
- Is more likely to develop in people who have other autoimmune diseases, like certain liver conditions, B12 deficiency, gluten sensitivity, rheumatoid arthritis, type 1 diabetes, lupus and Addisons disease .
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How Are Hypothyroidism And Hashimoto’s Thyroiditis Treated
Doctors treat an underactive thyroid with daily thyroid hormone replacement pills. The medicine is the same T4 that the body is no longer making. These will bring the body’s levels of thyroid hormone back to normal.
This treatment is fairly simple, but a person will have doctor visits several times a year for an exam, blood tests, and medicine changes as needed.
What Are Thyroid Antibodies
Antibodies are not inherently bad and are actually a very important part of our immune system. When the body detects foreign pathogens, such as bacterial or viral infections, it produces proteins called antibodies. These proteins help recruit other immune cells and fight off intruders.
However, in some people, the immune system goes awry and starts to produce antibodies against normal body tissue. In the case of thyroid autoimmune disorders, like Hashimotos hypothyroidism and Graves disease, the immune system mistakenly produces antibodies that attack the thyroid cells.
When they go unchecked, these antibodies can lead to inflammation in the thyroid known as thyroiditis. This destruction to the gland may eventually cause the person to enter a hypothyroid or hyperthyroid state.
Not everyone who has antithyroid antibodies is hypothyroid, but some people with elevated TPO, TSH, or TG antibodies will eventually become hypothyroid. Furthermore, some patients with thyroid disease may never show elevated levels of any thyroid antibodies .
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Why Might Your Doctor Test Your Thyroglobulin Antibodies Levels
Your doctor may check your TgAB levels if they suspect you have an underlying autoimmune condition causing thyroid dysfunction. A doctor may want to see the results of a TGAb test if they see specific clinical findings on your lab work and physical exam, including:
- Inflammation of the thyroid
- Abnormalities in other thyroid function tests like T4 and T3
While this may be a test occasionally used to detect autoimmune thyroiditis, it is more common to use this test to determine if treatment for thyroid cancer has been effective or not. Indeed, providers often use TgAB as a tumor marker because your body will only continue to produce TgAB’s if you still have thyroid tissue in your body. Thus, after thyroid cancer treatment, the goal is to have no TgAB’s in your lab work after your thyroid has been removed.
Antibodies To Thyroid Antigens
Table 1 provides a comparison of characteristics of anti-TSHR, anti-TPO, and anti-Tg antibodies.
Table 1. Characterization of different anti-thyroid antibodies.
Thyroid-Stimulating Hormone Receptor
After expression on the thyrocyte cell surface, the TSHR undergoes cleavage within the hinge region at two or more sites loss of a C-peptide like region leads to an extracellular A-subunit linked by disulfide bonds to the B-subunit . Subsequently, some A-subunits are shed. Substantial evidence suggests that the shed A-subunit is the autoantigen initiating and/or driving the autoimmune response to the TSHR in GD . As shown by crystallization, stimulating TSHR monoclonal antibody M22 and TSH blocking monoclonal antibody K1-70 bind to closely overlapping epitopes at the amino terminus . In addition, neutral antibodies directed against the hinge region exist . These antibodies can induce generation of oxidative radicals and induce apoptosis. The balance between stimulating TSHR and neutral antibodies can provide a balance between thyrocyte proliferation and apoptosis. DNA released from apoptotic cells stimulates the immune response. Since shedding of A-subunits occurs in all humans, the presence of exogenous and endogenous factors Factors and Endogenous Factors) is mandatory for the development of GD .
Thyroid Peroxidase
Thyroglobulin
Other Thyroid Antigens
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When Should I Get Testing For Thyroid Antibodies
It is not always necessary to test for thyroid antibodies to establish a diagnosis of an autoimmune disorder affecting the thyroid. However, doctors may find thyroid antibody testing helpful in the following situations:
- Subclinical hypothyroidism: In patients with a high TSH and a normal T4, testing for TPO antibodies may help predict whether the hypothyroidism will progress from being subclinical, in which it may not be causing significant or observable symptoms, to more severe and permanent dysfunction.
- Goiter: A goiter describes the abnormal enlargement of the thyroid gland. Some experts recommend testing for TPOAb in patients with a goiter, even if their thyroid hormone levels are normal.
- Hyperthyroidism, if the cause is not obvious: When patients have an overactive thyroid, sometimes it is clear from their physical examination and thyroid hormone tests that they have Graves disease. In less obvious cases, TRAb testing or imaging tests may be helpful in diagnosing or ruling out Graves disease.
- Monitoring after thyroid cancer treatment: Patients who are monitored with thyroglobulin testing after treatment may also have their TgAb levels tested as elevated TgAb can interfere with some thyroglobulin tests.
Although thyroglobulin antibodies may be elevated in both Hashimotos and Graves disease, it is not typically tested during diagnosis.
How Can I Check My Thyroid Function
You can assess your thyroid function in one of two ways. The first way is by seeing a doctor first and having them order bloodwork based on your physical exam and medical history. The second way is to check your thyroid levels before you meet with your doctor so you can talk about your lab results in your consultation.
Most doctors require that you see them first before they order bloodwork unless you have an established relationship. However, it may make more sense to have your labs in hand so you can talk directly about your results and what actions are necessary to help you feel your best.
To have your thyroid labs assessed ahead of time, you can order an at-home thyroid test kit to measure your TSH, free T4, free T3, and looks for TPO antibodies. You also have the option to add on vitamin D and/or reverse T3, which can add value to your discussion with your doctor as well. An at-home thyroid test requires only a finger-prick . It delivers comprehensive results to you within five days of the lab receiving your sample.
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What If You Dont Test Positive For Thyroid Antibodies Can You Still Have Hashimotos
Current medical reports state that 80-90 percent of people with Hashimotos will have TPO antibodies. That said, researchers at the University of Wisconsins Thyroid Multidisciplinary Clinic found that only half of the patients who tested positive for Hashimotos through cytology had TPO antibodies. This means that a person can have Hashimotos even if their thyroid antibody test is negative. This variant of Hashimotos is known as serum negative Hashimotos and is a less aggressive form of Hashimotos, so it will be slower developing.
Additionally, researchers have identified that the body may produce other thyroid antibodies, that are not yet available outside of research labs, but may also play a role in thyroid disease, including Sodium-iodine symporter and Pendrin . The clinical relevance of these antibodies is not yet understood, but as with all emerging research, we just want to be aware of it. NISAb is found in 17 percent of people with Hashimotos and Pendrin is found in 11 percent.
Ive included a chart from UpToDate that shows the estimated prevalence of these three antithyroid antibodies in various populations. Again, keep in mind that the more elevated these antibodies are, the more likely you are to progress to the stage that involves the destruction of your thyroid.
| < 35 IU/mL |
< 2 IU/mL |
Certain Conditions Can Make Your Thyroglobulin Antibody High
Even though antithyroglobulin antibodies are not the best predictor of thyroid disorders, they should not necessarily be ignored. Unlike TPO antibodies, thyroglobulin antibodies are not able to stimulate an immune response in the thyroid, but they may be useful in diagnosing certain thyroid conditions .
Anti-TG antibody levels may show importance in the following:
- Patients diagnosed with thyroid carcinoma who have elevated TG antibodies may be at a higher risk of the cancer spreading to lymph nodes or surrounding organs. Elevated levels may also indicate a high risk of thyroid cancer recurrence after treatment [4
- Trusted SourcePubMedGo to source].
One study found that after successfully treating thyroid disease, thyroglobulin levels dropped back down into normal reference ranges . It is important to point out that this study tested the actual levels of thyroglobulin protein, not the TG-antibody levels.
However, this finding is consistent with another study that found elevated anti-TG antibodies to correlate with the severity of hypothyroid symptoms, including fragile hair, swelling of the face and eyes, and vocal hoarseness [3
Thyroglobulin autoantibodies may not be the best indicator of thyroid disease, but likely will continue to be useful in the screening and monitoring of select conditions.
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What Are Tpo Antibodies
Antibodies are proteins produced by the body to protect against infections. However, sometimes they mistakenly attack your tissues, causing illness.
Thyroid peroxidase is an enzyme found in the thyroid gland that plays a vital role in producing thyroid hormones. TPO converts iodide ions absorbed from food into an active form of iodine to be used by the body.
The body needs iodine to make thyroid hormones. Iodine connects with tyrosine for the production of the thyroid hormones: thyroxine and triiodothyronine . If dietary iodine is deficient, the thyroid cannot produce sufficient thyroid hormone.
This lack of thyroid hormone creates negative feedback with the pituitary gland, which produces and releases thyroid-stimulating hormone . An increase in TSH signals additional production of TPO.
If antibody levels in the blood are elevated, it suggests that your immune system is attacking normal, healthy tissue.
Typically, the immune system safeguards against germs like bacteria and viruses. It can generally distinguish between foreign cells and your cells.
However, autoimmunity is a condition in which your immune system mistakenly attacks your body. It mistakes your cells as foreign and releases antibodies that attack healthy cells.
Some autoimmune conditions target only one part of the body, like Hashimoto’s thyroiditis , which targets the thyroid gland.
Can I have thyroid antibodies without hypothyroidism?
What Is Hashimotos Thyroiditis
Hashimoto’s thyroiditis is an autoimmune disorder that damages the thyroid gland. Autoimmunity occurs when immune cells attack healthy tissue instead of protecting it, leading to chronic inflammation.
In Hashimoto’s thyroiditis, immune cells mistakenly attack the healthy thyroid tissue, causing inflammation of the thyroid. This damage can eventually lead to inadequate thyroid hormone production. Without enough thyroid hormones for your body to function correctly, you develop hypothyroidism.
Hashimoto’s thyroiditis is the leading cause of hypothyroidism in the United States, affecting roughly 5% of the population.
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Thyroid Antibody Test Results
Antibody levels can be tested with a blood sample. The antibody test measures the amount of antibody per milliliter or liter of blood in “international units.”
Normal values are:
- TPO antibody: Less than 9 IU/mL
- Thyroid-stimulating immunoglobulin antibody : Less than 1.75 IU/L
- Anti-Tg antibody: Less than 4 IU/mL
Note that different laboratories may have different normal range values.
Recommendations For High Tpo Treatment
As experts suggest that with the correct amalgamation of medications, nutrition, and diet, you can reduce thyroid antibodies and its symptoms. Start focussing on the whole, unprocessed foods and eat fresh foods rather than frozen ones.
People with high TPO should be open to trying dissimilar eating habits until they find the one that best suits them.
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Other Thyroid Antibodies Like Tpo May Be More Useful
Thyroid peroxidase antibody levels are a much stronger indicator of an increased risk for thyroid disease. TPO antibodies are 90% sensitive in detecting thyroiditis, and are effective in monitoring the progression and severity of thyroid conditions [2
Trusted SourcePubMedGo to source]. However, monitoring anti-TPO antibodies come with their own limitations.
The normal reference range for TPO antibodies is less than 35 IU/mL. But a 2016 study published in the Journal of Hormone and Metabolic Research [9
- Those who had TPO antibodies below 500 IU/mL had a low risk of future progression to hypothyroidism.
- Those who were above 500 IU/mL still only had a moderate risk.
The Tehran Thyroid Study, which followed the course of thyroid disease in a large cohort of people over nine years, showed similar results: those with elevated TPO antibodies only had a 9-19% chance of becoming hypothyroid after 6 years of follow up .
If we consider this, elevated thyroid antibodies are not as consequential as many thyroid experts would suggest.
Ive commonly seen people with Hashimotos disease or elevated thyroid antibodies become hyper-focused on reducing their antibody test results to the normal reference range, and becoming unnecessarily stressed. The research suggests this isnt necessary.
Do Thyroglobulin And Thyroid Peroxidase Antibodies Have A Pathogenic Role
Tg-Ab and TPO autoantibodies appear to be a secondary response to thyroid injury and are not thought to cause disease themselves, although they may contribute to its development and chronicity. Both types of antibodies are polyclonal, and although they are of the immunoglobulin G class, they are not restricted to one particular immunoglobulin G subclass. Polyclonality also mitigates against a primary role in disease pathogenesis.214,215 For example, these thyroid antibodies cannot transfer disease from mother to fetus or between animals even though they can pass across the placenta. However, both antibodies may contribute to disease mechanisms. For example, TPO-Ab on the surface of B cells may be involved in antigen presentation, thus activating thyroid-specific T cells.216 Such autoantibodies may have complement-fixing cytotoxic activity. And TPO-Ab, in particular, correlates well with thyroid damage and lymphocytic infiltration.
Aisha Sheikh, in, 2021
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Stage : Hashimotos Progresses And There Is A Progression To Other Immune Disorders
In stage 5, as Hashimotos progresses, we unfortunately have a progression to other immune disorders as well. At this time, a person may get diagnosed with Rheumatoid Arthritis, Lupus or any of the other types of autoimmune conditions.
So as you look at the progression of disease, note that our earliest warning about Hashimotos, and our best opportunity for early intervention, is during Stage 2 when we initially find evidence of thyroid antibodies.
How Is Hashimoto’s Thyroiditis Treated
Your healthcare provider will figure out the best treatment for you based on:
- Your age, overall health, and medical history
- How sick you are
- How well you handle certain medicines, treatments, or therapies
- If your condition is expected to get worse
- Your opinion or preference
You will not need treatment if your thyroid hormone levels are normal. But Hashimoto’s thyroiditis often looks like an underactive thyroid gland. If so, it can be treated with medicine. The medicine replaces lost thyroid hormone. That should stop your symptoms. It can also ease a goiter if you have one. A goiter can cause problems like pain or trouble swallowing, breathing, or speaking. If these symptoms don’t get better, you may need surgery to remove the goiter.
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Understanding That Hashimotos Thyroiditis Is Progressive
In the early stages, the body compensates and produces more hormones to keep your hormone levels within “normal” ranges. Here, your thyroid is still close to fully functional. While TPO antibodies may be present in the blood, marking the presence of an autoimmune condition, it could take several years before hypothyroid symptoms appear.
Progressively, as TPO antibodies destroy more thyroid tissue, the thyroid gland loses the ability to compensate. You begin to become deficient in thyroid hormone, and you might start to feel symptoms.
Eventually, the gland completely loses its ability to produce thyroid hormone, considered the end-stage of Hashimoto’s thyroiditis.