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What You Need To Know About Thyroid Stimulating Immunoglobulins

I’ve written separate articles on thyroid peroxidase (TPO) antibodies and anti-thyroglobulin antibodies, but I haven’t put together a post on thyroid stimulating immunoglobulins…until now!  These antibodies are associated with Graves’ disease, and it’s unfortunate that some endocrinologists don’t test their hyperthyroid patients for these antibodies, but instead will test the TPO and/or anti-thyroglobulin antibodies.  While it’s common for people to have two or three different thyroid antibodies, everyone with hyperthyroidism should get the thyroid stimulating immunoglobulins tested.

So what are thyroid stimulating immunoglobulins (TSI), and how do they differ from other types of thyroid antibodies?  TSI are a type of thyrotropin (TSH) receptor antibody (TRAB). There are actually two types of TSH receptor antibodies. In addition to thyroid stimulating immunoglobulins, there are also thyroid binding inhibitory immunoglobulins (TBII), which is a type of thyrotropin receptor blocking antibody.  These antibodies bind to the TSH receptor and inhibit the binding of TSH, thus blocking the synthesis and secretion of thyroid hormones.  These aren’t commonly tested, and one reason is because not all labs offer this.

What Do Elevated TSI Levels Indicate?

Elevated TSI levels are associated with Graves’ disease.  What happens is that the TSI bind to the TSH receptors, which results in the excessive production of thyroid hormone.  This is why most people with Graves’ disease have hyperthyroidism, although some people have subclinical Graves’ disease, which is when the TSI are elevated, the TSH is depressed, but the thyroid hormone levels are within the lab reference range.

What Causes Elevated Thyroid Stimulating Immunoglobulins?

As I have mentioned, elevated TSI levels are associated with Graves’ disease, which is an autoimmune condition.  In the past I’ve discussed the triad of autoimmunity [1], and according to this, in order for autoimmunity to develop the following three factors need to be present: 1) genetic predisposition, 2) exposure to an environmental trigger, 3) a leaky gut.  So just as is the case with any autoimmune condition, someone with elevated TSI levels has a genetic predisposition for Graves’ disease, but having the genetics alone doesn’t mean they will develop thyroid autoimmunity, as they will need to be exposed to an environmental trigger and have a leaky gut.

What Is The Lab Reference Range?

Unfortunately different labs will use different units of measurements, and you can’t compare them with one another.  For example, the Labcorp reference range is 0.00-0.55 IU/L, whereas the reference range for Quest Diagnostics is <140%.  As for the thyrotropin (TSH) receptor antibody test, Labcorp has a reference range of 0.0−1.75 IU/L, while Quest Diagnostics has a range of ≤2.00 IU/L.  If at all possible I recommend getting the thyroid stimulating immunoglobulins tested, although it of course is fine to get both the TSI and TRAB tested.

Some reading this might wonder what the “optimal” reference range is for these markers, and whether the goal should be to have a level of zero.  While you want the levels to be well below the lab reference range, I wouldn’t say that they have to be zero in order for someone to be in a state of remission.  As for the optimal reference range, I like to see the TSI less than 80% or less than 0.30 IU/L, although this is just what I look for, as I haven’t seen any other practitioners list optimal reference ranges.  It’s also important to mention that some labs don’t reveal a numerical value below the reference range.  For example, if the TSI is below the reference range it might show up on the report as <0.55 IU/L or <120%.

The Relationship Between Thyroid Stimulating Immunoglobulins and Thyroid Eye Disease

Because a higher TSI level usually indicates a more vigorous immune system response, typically the higher the TSI, the more likely someone is to have thyroid eye disease [2].  For example, if someone has a TSI greater than 300% they are more likely to have thyroid eye disease symptoms when compared to someone with a TSI less than 300%.  Of course there are always exceptions, as I’ve had patients with very high TSI levels who didn’t experience any signs or symptoms of thyroid eye disease.

How Can You Decrease Thyroid Stimulating Immunoglobulins?

As for how to decrease and normalize thyroid stimulating immunoglobulins, the approach is similar to lowering other autoantibodies:

1. Find and remove your triggers. I mentioned the triad of autoimmunity earlier, and exposure to an environmental trigger is one of the factors that causes the development of an autoimmune condition.  As a result, it makes sense that in order to reverse the autoimmune component and lower thyroid stimulating immunoglobulins you will need to find and remove any immune system triggers.

2. Heal the gut. Another component of the triad of autoimmunity is a leaky gut, and so you of course need to heal the gut.  Check out the blog post I wrote on the “5R protocol [3]” for more information on how to heal your gut.  But I’ll say here that you usually need to do more than take probiotics and gut healing agents, as these won’t be effective if you don’t address the factor that is compromising the gut.  For example, if someone has a gut infection that is causing a leaky gut, this needs to be addressed. Similarly, if someone is eating gluten and this is causing a leaky gut, you can’t fix this problem by taking digestive enzymes, probiotics, and drinking bone broth.  In this situation you would need to eradicate the gut infection.

3. Correct other imbalances.  Other imbalances can also be a contributing factor.  For example, having certain nutrient deficiencies can make someone more susceptible to developing an autoimmune condition, such as selenium [4].  In fact, the research shows that selenium can potentially lower both TSH receptor antibodies and TPO antibodies (1) [5], although you still need to remove the trigger and heal the gut.

4. Break the chronic inflammatory cycle.  While removing the triggers and healing the gut will usually resolve the inflammation, this isn’t always the case.  Sometimes additional measures need to be taken in order to break this cycle, such as taking high doses of natural anti-inflammatory agents (vitamin D [6], EPA and DHA, curcumin, resveratrol).  Low dose naltrexone [7] might also help to break the chronic inflammatory cycle, and thus is something to consider, although I would first try the natural anti-inflammatory agents.

Do You Have Elevated Thyroid Stimulating Immunoglobulins?

If you have elevated TSI levels, I’d love to hear if you have done anything to try to lower them.  Perhaps you took a natural treatment approach, natural anti-inflammatory agents, low dose naltrexone, or did something else to modulate your immune system.  Either way, please feel free to share your experience in the comments section below.