Although I’ve written numerous articles and blog posts on thyroid antibodies, I’ve decided to dedicate a blog post to thyroid peroxidase (TPO) antibodies. There are a few different types of thyroid antibodies, but I’d like to focus on TPO antibodies because they are the most common type of thyroid antibody. Although they are more commonly associated with Hashimoto’s thyroiditis, TPO antibodies are frequently elevated in Graves’ disease as well.
So what are TPO antibodies, and what differentiates them from other types of autoantibodies? First of all, TPO antibodies develop when the immune system attacks thyroid peroxidase. What is thyroid peroxidase? Thyroid peroxidase is an enzyme that plays a major role in the synthesis of thyroid hormone. This enzyme converts iodide to iodine, and the iodine combines with tyrosine on thyroglobulin, which forms thyroxine (T4) and triiodothyronine (T3). So when someone has elevated TPO antibodies, this indicates that the immune system is attacking the thyroid peroxidase enzyme, which in turn can inhibit the production of thyroid hormone, thus eventually leading to hypothyroidism.
It’s worth mentioning that there also is a thyroid peroxidase (TPO) gene. Some people will have genetic polymorphisms (mutations) of the TPO gene, which can lead to severe defects in thyroid hormone production due to total iodide organification defects or partial iodide organification defects (1). One study identified six different genetic defects of the TPO gene, and found that three of these are significantly associated with hypothyroidism (1).
Are people with Hashimoto’s and Graves’ disease who have anti-TPO antibodies more likely to have genetic polymorphisms of the TPO gene? The studies are conflicting, as some show no association, while other studies did demonstrate an association between TPO genetic defects and anti-TPO antibodies (2). With genetic testing more popular these days you might wonder if you can get tested to see if you have any TPO polymorphisms. As of writing this article I’m unaware of any labs available to the public which conducts this type of testing, although I’m sure it’s only a matter of time before it becomes readily available.
TPO Antibodies In Other Autoimmune Conditions
According to the research, anti-TPO antibodies are detected in 90 to 95% of those with autoimmune thyroid conditions, including 80% in those who have Graves’ disease (3). It’s common for those with other autoimmune conditions to have elevated anti-TPO antibodies, as one study showed that anti-TPO antibodies were present in 37% of those with rheumatoid arthritis (4). Another study showed that approximately 39.6% of people with type 1 diabetes had anti-TPO antibodies (5). In celiac patients, anti-TPO antibodies have been detected in 11.7 to 30.5% of patients (6), although other studies have shown a higher percentage (7).
What Causes Elevated TPO Antibodies?
In other blog posts and articles I’ve discussed the triad of autoimmunity. This is also known as the 3-legged stool of autoimmunity, and it includes 1) a genetic predisposition, 2) exposure to an environmental trigger, and 3) an increase in intestinal permeability (a leaky gut). So the reason why one person might develop elevated anti-TPO antibodies, while another person will develop thyroid stimulating immunoglobulins, is because they have different genetics that predispose them to different autoimmune conditions, and thus different autoantibodies. Some people have both anti-TPO antibodies and thyroid stimulating immunoglobulins, which means they have the genetic markers for these two autoantibodies.
But just because someone has a genetic predisposition for developing anti-TPO antibodies doesn’t mean they will develop them. Once again, according to the triad of autoimmunity, they also need to be exposed to a trigger and at the same time have a leaky gut. I have discussed some of the different triggers of thyroid autoimmunity in different articles and blog posts, as well as in my books on Graves’ disease and Hashimoto’s. I’ve also written numerous articles and blog posts on leaky gut syndrome, with my latest one entitled “5 Things To Know About Leaky Gut Syndrome”.
What Is The Reference Range?
Just as is the case with other markers, different labs will have different reference ranges. For example, the TPO antibodies reference range for Quest Diagnostics is <9 IU/mL. On the other hand, the reference range for Labcorp is 0−34 IU/mL. You might wonder what the “optimal” reference range is, and while this is debatable, there is no question that you want to see this value as low as possible, and so I prefer to see it <9 IU/mL.
It’s also important to mention that higher TPO antibodies don’t necessarily correlate with how much damage is taking place to the thyroid gland. Don’t get me wrong, as just like most natural healthcare practitioners, I like to see these and other autoantibodies decrease, and eventually normalize. But if someone’s TPO antibodies is 1,000 IU/mL, this doesn’t mean that it’s ten times more severe than someone whose TPO antibodies are 100 IU/mL.
The Relationship Between Thyroid Peroxidase and Iron
Thyroid peroxidase is a heme-containing enzyme (8), which means that it requires iron to function properly. As a result, it shouldn’t be surprising that a few studies show that iron deficiency anemia can impair thyroid metabolism by reducing TPO activity (8) (9). Another study showed that iron deficiency anemia not only can lead to hypothyroidism, but elevated TPO antibodies (10).
Iron deficiency anemia is so important that a few years ago I dedicated an article on this topic. One of the big problems is that many medical doctors will only test for serum iron or ferritin, instead of ordering a full iron panel. Another problem is that most will rely on the lab reference ranges. So for example, someone might present with a ferritin of 18 ng/mL, which is considered to be normal by most labs, yet is well below optimal. Also keep in mind that inflammation can increase ferritin, and so if someone has normal or high ferritin levels, this alone won’t rule out an iron deficiency.
How Can You Decrease TPO Antibodies?
If you have elevated anti-TPO antibodies, or any other type of autoantibody, you will need to do the following to decrease and normalize these:
1. Remove the autoimmune trigger. It makes sense that the autoimmune trigger needs to be removed in order to decrease autoantibodies and to help the person get into a state of remission. It can be challenging to find someone’s triggers. In fact, that’s why I wrote and released the book Hashimoto’s Triggers earlier this year! My goal isn’t to plug my book here, but I really do believe it’s the most comprehensive book on finding and detecting autoimmune triggers. And while the book was written for Hashimoto’s patients, a lot of the information can also benefit people with other autoimmune conditions, including Graves’ disease.
2. Heal the gut. Since a leaky gut is part of the triad of autoimmunity, it shouldn’t be surprising that healing the gut is also necessary to decrease TPO antibodies. While it’s common for people to take gut healing nutrients such as L-glutamine, and consume gut healing foods such as bone broth, for optimal gut health you need to reduce the factor that is causing the leaky gut in the first place. For example, if you have a gut infection that is causing a leaky gut, you can supplement with L-glutamine and drink bone broth every day and you won’t heal your gut until the infection has been eradicated.
3. Reduce proinflammatory cytokines and increase glutathione levels. Proinflammatory cytokines are a factor in autoimmunity, and while removing the trigger and healing the gut can help to reduce inflammation, you might have to do other things to reduce proinflammatory cytokines. Speaking of proinflammatory cytokines, an interleukin called IL-17 plays a key role in autoimmunity, and when IL-17 binds to its receptor it causes the production of other proinflammatory cytokines, including IL-1, IL-6, and TNF-alpha. Some of the factors which can decrease proinflammatory cytokines include vitamin D, fish oils, and curcumin.
Vitamin A also can play an important role in reducing IL-17. It does so by turning on something called FOXP3, which will lead to a greater production of regulatory T cells (Tregs) and less Th17 cells. Th17 cells are one of the IL-17 producing cells. On the other hand, Tregs play a role in suppressing autoimmunity. So essentially you want a lot of Tregs and a low number of Th17 cells.
As for glutathione, this is a potent antioxidant that can help to reduce oxidative stress associated with autoimmunity. Glutathione peroxidase can help to reduce free radicals (11), which can also decrease proinflammatory cytokines. Many people with autoimmune conditions such Graves’ disease and Hashimoto’s have a glutathione deficiency. This is important to bring up, as if someone has a glutathione deficiency but does other things to reduce proinflammatory cytokines (i.e. take fish oils), then this alone won’t be sufficient to decrease TPO antibodies. This is one reason why a few studies show that taking selenium can decrease thyroid antibodies (12) (13). Selenium is a cofactor of glutathione peroxidase, and thus a selenium deficiency can cause a glutathione deficiency.
While it’s important to increase glutathione levels, which can be accomplished through diet and/or supplementation, you also want to address the cause of what’s depleting the glutathione. In a recent article I wrote entitled “Glutathione and Thyroid Autoimmunity” I discussed some of the factors that can deplete glutathione, which includes environmental toxins, acetaminophen and other medications, alcohol consumption, and nutrient deficiencies.
4. Correct other imbalances. While arguably the first three things mentioned here are the most important factors when trying to decrease TPO antibodies, you also want to correct other imbalances that may be present. As an example, cortisol plays an important role in controlling inflammation. As a result, if someone has compromised adrenals that presents as depressed cortisol levels, then it will be challenging to decrease proinflammatory cytokines.
I’ve written a few blog posts where I discussed the relationship between oral health and thyroid health. A few studies have shown that periodontal disease can cause an increase in Th17 cells (14) (15), which are associated with Hashimoto’s and other autoimmune conditions. And while more research has focused on the correlation between rheumatoid arthritis and periodontal disease (16) (17), there is also evidence that Hashimoto’s thyroiditis can be associated with periodontal disease (18). More research is needed in this area as well, but if you have inflamed gums it’s possible this needs to be addressed in order to restore your health.
Are TPO Antibodies Protective Against Breast Cancer?
I found it interesting that some studies show that there is a protective effect of anti-TPO antibodies for women with breast cancer (19). The studies show that women with breast cancer who also had elevated TPO antibodies had better survival rates (20). The authors of one study hypothesized that breast TPO may participate in the regulation of oxidative stress in breast tissue (21).
In summary, thyroid peroxidase (TPO) antibodies are the most common type of thyroid antibody. Although they are more strongly associated with Hashimoto’s, 80% of those with Graves’ disease will have elevated TPO antibodies. As for what causes elevated TPO antibodies, according to the triad of autoimmunity someone needs to have a genetic predisposition, exposure to an environmental trigger, and a leaky gut in order to develop autoimmunity, and thus elevated autoantibodies. As a result, in order to decrease TPO antibodies you need to find and remove the autoimmune trigger, heal the gut, and you might also need to do other things to reduce proinflammatory cytokines and increase glutathione levels. As discussed in this blog post, correcting other imbalances might also be necessary to lower TPO antibodies.
Tammy says
Mine are very high along with many other symptoms. Seems as though I learn something new about this condition daily. It’s very overwhelming and to the point debilitating. People don’t understand the health condition and think you’re over reacting. It’s real it’s me. If you don’t have money to pay for functional medicine dr. you’re stuck, you get no help. Insurance doesn’t want you better and won’t pay for what is needed. I find myself asking how why and where to turn for help. Symptoms just compound and feel yourself sinking deeper and deeper. Fear of what’s going to happen next and then it’s there.
Sharlene says
Tammy I feel the exact same way. I have Graves but when on Methimazole go hypo to the point that I don’t even want to get out of bed. I struggle to get thru the work day. Then the couple times I have been off the medication I get hyper again and my antibodies are always in the 200s. Very frustrating because people don’t understand how you feel. I also would love to see a natural doctor but the cost is overwhelming and all the endocrinologists want to do is radiation or surgery.
DeAnna says
I struggle against medical tyranny too. After I pointed a thyroid nodule out to my doctor he ran the blood test. The following day his nurse called and told me that there was a scrip waiting for me at my pharmacy. When I called the pharmacy I was told that the scrip was for Synthroid. I went online and read the patient reviews for Synthroid and was horrified! These people were suffering the tortures of the damned. When I went back to the doctor he was so incensed that I refused the Synthroid that he wouldn’t even tell me what my T-3 and T4 numbers were. When I asked if it was hypothyroidism or Hashimoto’s he SHOUTED at me that it “doesn’t matter!” Sites like this are the only recourse I have, and I’m not even sure what my diagnosis is, though some diet changes and supplements have helped and the nodule has shrunk and no longer hurts. I would give my eye teeth to be able to work with a naturopath or other sane, reasonable doctor. I agree with Tammy, the medical establishment doesn’t want anyone to get well and doctors are trained/brainwashed accordingly.
Mrs VW says
DeAnna:
FIND ANOTHER DOCTOR! And preferably one that is a functional medicine doctor who will find the root cause!! Not just give you a pill!
Traci Petersen says
My doctor says that I don’t need to check my antibody level for a year, since the immune system has a very good memory. How quickly can antibodies decrease?