Thyroglobulin Antibodies in Hashimoto’s and Graves’ Disease

Anti-thyroglobulin antibodies are one of three main types of thyroid autoantibodies, and they are commonly associated with Hashimoto’s thyroiditis.  However, it’s not uncommon for those with Graves’ disease to also have elevated anti-thyroglobulin antibodies (along with elevated TSH receptor antibodies).  In this blog post I’m going discuss anti-thyroglobulin antibodies in detail.

So why do anti-thyroglobulin antibodies develop?  Well, anti-thyroglobulin antibodies develop when there is damage to thyroglobulin, which is a glycoprotein secreted by follicular cells of the thyroid gland.  The most common reason for damage to thyroglobulin is from the autoimmune process of Hashimoto’s Thyroiditis.

According to the triad of autoimmunity, in order for an autoimmune condition to develop you need 1) a genetic predisposition, 2) exposure to an environmental trigger, and 3) a leaky gut.  In the past I wrote a blog post on thyroid peroxidase (TPO) antibodies, and I discussed how there can be genetic variations of the TPO gene, which in turn can affect thyroid hormone production.  As for thyroglobulin, the research suggests that there is a possible correlation between thyroglobulin gene polymorphisms and thyroid autoimmunity (1) (2).  In other words, having variations in the thyroglobulin gene can increase the risk of someone developing Hashimoto’s thyroiditis.

Anti-thyroglobulin Antibodies: Hashimoto’s vs. Graves’ Disease

As I mentioned in the opening paragraph, anti-thyroglobulin antibodies are more closely associated with Hashimoto’s thyroiditis, although they are also common in those with Graves’ disease.  As for their prevalence, it depends on the source, as one source stated that the prevalence of anti-thyroglobulin antibodies was 60-80% in Hashimoto’s and 50-60% in Graves’ disease patients, where another source stated that they were identified in 70-80% of those with Hashimoto’s, and 30-40% of Graves’ disease patients (3).  What’s the significance of having elevated anti-thyroglobulin antibodies?  Well, besides confirming the presence of an autoimmune response, having elevated anti-thyroglobulin antibodies usually means that damage is taking place to thyroglobulin.  And since thyroglobulin plays an important role in thyroid hormone production, if sufficient damage to thyroglobulin takes place this can eventually result in hypothyroidism.

Of course we also need to keep in mind that many people with both Hashimoto’s and Graves’ disease have anti-TPO antibodies, which also can lead to hypothyroidism.  And while having anti-TPO and/or anti-thyroglobulin antibodies doesn’t guarantee that the person will develop overt hypothyroidism, I think it’s safe to say that if someone has both of these thyroid antibodies there is a greater chance of them developing overt hypothyroidism in the future when compared with someone who only has one of these thyroid autoantibodies.  Many people with Hashimoto’s don’t present with overt hypothyroidism, as while many will have an elevated TSH, their thyroid hormone levels are commonly within the lab reference range, although frequently below the optimal reference range.  Either way, the goal is to do things to improve the health of the person’s immune system so that further damage to the thyroid gland doesn’t take place.

What is The “Normal” Reference Range of Anti-Thyroglobulin Antibodies?

Although different labs commonly have different reference ranges, as of 2020, the range of anti-thyroglobulin antibodies according to both Labcorp and Quest Diagnostics is <1 IU/mL.  However, other labs use different methodologies which can result in different reference ranges.  For example, if you visit the Labcorp website and do a search for anti-thyroglobulin antibodies, the methodology currently used is called “Immunochemiluminometric assay (ICMA)”.  On the lab reports they specifically say that it’s “measured by Beckman Coultor Methodology”.  However, I had a patient get the anti-thyroglobulin antibodies tested at a different lab that used the “Rouche Elecays electrochemiluminesence method”, and the reference range was 0-115 IU/mL.

In addition, on the lab report it stated that “Thyroglobulin antibody results cannot be compared across different methods.”  So even if the units of measurement are the same between labs (i.e. IU/mL), due to different testing equipment, chemical reagents used, and analysis techniques you can’t necessary compare results from different labs, which is one reason why it’s a good idea to try to use the same lab on a regular basis.

As an example, in May of 2019 I had a patient who tested the anti-thyroglobulin antibodies through Vibrant America and had a value of >4,000 IU/mL.  In August of 2019 she retested the anti-thyroglobulin antibodies at Labcorp and had a value of 43.2 IU/mL, and two months later she retested them through Vibrant America and the value was once again >4,000 IU/mL.  Of course ultimately you want the thyroid antibodies to normalize regardless of which lab you use, but I’m just using this example to demonstrate why you can’t always compare the same marker using different labs.

Serum Thyroglobulin vs. Anti-Thyroglobulin Antibodies

It’s also important to mention that there is a separate test for serum thyroglobulin.  Once again, thyroglobulin is a protein produced by the cells of the thyroid gland, and normally its concentration in blood is low.  But there are a few factors that can increase serum thyroglobulin levels.  First of all, having elevated anti-thyroglobulin antibodies can cause an elevation in serum thyroglobulin levels.  Second, it can also be elevated in some cases of thyroid cancer, including thyroid adenoma, thyroid papillary and follicular cancer.  So in some cases thyroglobulin is used as a tumor marker.

A third reason why serum thyroglobulin can be elevated is because someone has an iodine deficiency.  This is an overlooked cause of elevated serum thyroglobulin levels, but numerous studies shows that thyroglobulin can be used as a functional biomarker of iodine status (4) (5) (6).  I usually don’t rely on this marker to determine if someone has an iodine deficiency, as I like urinary iodine testing.  But some feel that thyroglobulin is a superior marker because it reflects long-term iodine intake.

Additional Information On Anti-Thyroglobulin Antibodies

Before talking about how to lower anti-thyroglobulin antibodies, it’s important to mention that most conventional medical doctors, including endocrinologists, don’t pay much attention to thyroid antibodies.  Some don’t test them at all, while many medical doctors will test them initially for diagnostic purposes.  But since most medical doctors don’t do anything to improve the health of the person’s immune system, they won’t typically retest the thyroid antibodies to see if they decrease.

It’s also worth mentioning that there isn’t always a correlation between high anti-thyroglobulin antibodies and the severity of the autoimmune process.  In other words, if someone has anti-thyroglobulin antibodies that are 100 IU/mL, while someone else has anti-thyroglobulin antibodies that are 1,000 IU/mL, this doesn’t mean it will be more challenging to restore the health of the person with the higher thyroid antibodies.  It really does come down to finding triggers and correcting other imbalances.

For example, if someone has very high anti-thyroglobulin antibodies and their triggers are found and removed relatively quickly, it’s likely for the thyroid antibodies to normalize faster than someone who has much lower anti-thyroglobulin antibodies and the triggers aren’t found and addressed.  This should make sense, although as I’ll mention below, sometimes removing the triggers doesn’t stop the inflammatory process associated with the autoimmune component.

How To Lower Anti-Thyroglobulin Antibodies

I just mentioned how lowering thyroid antibodies comes down to finding and removing triggers, along with correcting other underlying imbalances.  I also mentioned how if someone finds and removes their triggers relatively quickly then their thyroid antibodies can normalize quickly.  That being said, I don’t want to give anyone the impression that restoring the autoimmune component of someone with Hashimoto’s or Graves’ disease is a quick and easy process, as this usually isn’t the case.  For example, if someone finds their triggers quickly, it still usually takes time to lower and normalize their thyroid antibodies.  And of course if it takes awhile for someone to find their triggers it will take a longer amount of time to restore their health.

But either way, the first step to lower anti-thyroglobulin antibodies is to find and remove your triggers.  Sometimes this is as easy as changing your diet and eliminating certain food allergens, but many times it’s more complex than this.  Testing is usually required to find the triggers, and at times it can be challenging to know what testing is needed.  I deal with this in my practice on a daily basis, and I’ve discussed this in past articles and blog posts, as I try to be more conservative when it comes to testing because I don’t want the person to spend more money than they have to, but I also don’t want to be too conservative and miss something important.

Don’t Forget To Incorporate The 5-R Protocol

In addition to finding and removing autoimmune triggers, since a leaky gut is part of the triad of autoimmunity, it makes sense to do things to heal the gut.  In the past I have spoken about the 5-R protocol, which involves the following 5 components:

1. Remove the factor that’s causing the leaky gut.

2. Replace (i.e. digestive enzymes, stomach acid, dietary fiber)

3. Reinoculate (with pre- and probiotic foods and supplements)

4. Repair the gut

5. Rebalance through stress management, adequate sleep

It’s also important to mention that while removing the triggers and healing the gut will frequently resolve the inflammatory process, this isn’t always the case.  There is a transcription factor called Nuclear Factor Kappa B (NF-kB), and the deregulated activation of NF-kB may contribute to autoimmunity and inflammation (7).  What happens is that NF-kB becomes chronically activated, and sometimes outside help is needed to inactivate it.

Some of the natural agents that have been shown to inhibit NF-kB include turmeric, resveratrol, vitamin D, ginger, and omega-3 fatty acids.  While many people  with autoimmune conditions take one or more of these, remember that you also need to find and remove the triggers (and heal the gut).  While taking some natural anti-inflammatory agents initially can be beneficial, the point here is that in some cases it might be even more important to take them AFTER the triggers have been removed and the gut has been healed.

This is just one of the many complexities of autoimmunity, and admittedly when a patient of mine has followed my recommendations, yet their antibodies haven’t significantly lowered, there are times when I will question whether all of their triggers have been found and removed.  But in some cases the triggers may have been found and removed, but the chronic activation of NF-kB is still present.  The challenge is that there is no way to measure NF-kB outside of a laboratory setting, and so if someone has followed a natural treatment protocol and their autoantibodies are still elevated, the practitioner and patient has to decide whether further testing is the best option, or if the person should instead do things to inhibit NF-kB.

What’s Your Experience With Anti-Thyroglobulin Antibodies?

If you currently have elevated anti-thyroglobulin antibodies, or have had elevated anti-thyroglobulin antibodies in the past, I’d love to hear if you have done anything to try to decrease them.  Did changing your diet help?  Perhaps there was another trigger you found that was responsible for your elevated anti-thyroglobulin antibodies.  If you have elevated anti-thyroglobulin antibodies but haven’t had any success lowering them, feel free to share your experience as well.  Thank you!

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