Thyroid Stimulating Immunoglobulin (TSI): Patient Guide to Graves’ Disease

What does thyroid stimulating immunoglobulin mean?

Do your results correlate with the severity of your hyperthyroidism?

Is there a way to lower your antibody levels?

You probably already know that the presence of these antibodies may be an early warning sign that your body is suffering from an autoimmune disease, but what are you supposed to do about them?

Learning more about the TSI lab test can help you to understand your condition and understand treatment options

More...

What is Thyroid Stimulating Immunoglobulin? 

Thyroid stimulating immunoglobulin or TSI for short (1) is the name of a blood test which is used to identify the presence of autoimmune disease in those with hyperthyroidism. 

An abnormally high level of TSI in your body is highly predictive of a condition known as Graves' disease (2). 

Graves' disease is an autoimmune disease of the thyroid gland in which your body produces antibodies which sit on and activate thyroid hormone production. 

This production results in high levels of thyroid hormone which causes the symptoms of hyperthyroidism. 

Graves' disease is only one cause of hyperthyroidism so it's important to order this test if you have hyperthyroidism to help determine the CAUSE of your condition. 

TSI should be differentiated from other thyroid antibodies such as thyroglobulin antibody and thyroid-peroxidase antibody which tend to cause a different thyroid condition known as Hashimoto's thyroiditis

This patient guide will help you understand if your TSI levels are abnormal, what to do if you suspect Graves' disease, why it's important to monitor your antibody levels and how to potentially reduce them

Reference Range & Interpreting Your Lab Results

How do you know if your antibody levels are optimal?

When it comes to TSI (thyroid stimulating immunoglobulin) testing you'll find that there is a standard "reference range". 

This range is developed based on "normal" healthy adults and if you fall within this range you are considered to also be "normal". 

But let's break this down a little bit more:

If the presence of antibodies in your body mean that there is a chance that you may have an autoimmune disease, doesn't it make sense to want this number as close to zero as possible

I would tend to agree with you on that, and therefore I tend to prefer when patients have a TSI level which as close to zero as possible. 

The standard range for TSI is measured as a percentage and the cut off for normalcy is usually less than 1.4 (140%) or 1.3 (130%) (3).

This means that you can have a result of 130% and still be considered "normal" even though you are rapidly approaching the high end of that range. 

The "high end" of the normal range is considered to be 140% which means that the closer you get to this range the closer you are to developing abnormal test results and the closer you are to a diagnosis of Graves's disease. 

Because of this, it is preferable to have your percentage as far away from that "high end" as possible, in this case as far away from 140% as possible.  

Thyroid Function Tests Associated with High TSI

If your TSI lab tests are abnormal then your doctor will also order several tests to identify the function of your thyroid gland. 

These tests are often ordered at the same time, but in some cases you may need to go back for repeat testing. 

This is important because not every single case of elevated TSI is indicative of Graves' disease, so testing your thyroid function can weed out those who are outliers. 

In the presence of high TSI levels and hyperthyroid symptoms your thyroid function tests will most likely resemble this pattern:

  • TSH (thyroid stimulating hormone) - Low or suppressed
  • Free T3 - High
  • Free T4 - High or normal

This pattern is highly indicative of a hyperthyroid state in your body and an indication that you may also be suffering from Graves' disease. 

Symptoms Associated with Elevated TSI

The presence of thyroid stimulating immunoglobulin has a very specific effect on your thyroid gland. 

As the name describes, these antibodies attach to your thyroid gland and "stimulate" it. 

What does it mean if your thyroid gland is "stimulated"?

In this case, it means that they force your body to autonomously (without normal feedback loops) produce thyroid hormone. 

This causes a condition known as hyperthyroidism or thyrotoxicosis as your body struggles to cope with high levels of thyroid hormone. 

Under normal conditions, you want a small and steady amount of thyroid hormone in your body, but when this level becomes too high you may begin to experience certain symptoms. 

Because your thyroid helps to regulate your metabolism, gastrointestinal function, your weight, hair growth and so on, you might expect that these tissues start to suffer as your thyroid levels fluctuate. 

And that's exactly what happens as thyroid levels increase. 

Your body begins to speed up and you may experience any or all of the following symptoms:

  • Hair loss (as hair turnover increases)
  • Fatigue (due to overconsumption of energy and ATP)
  • Weight loss (as your metabolism speeds up)
  • Diarrhea (as your intestinal tract speeds up)
  • Heart palpitations or a rapid heart rate (as your heart rate speeds up)
  • Tremors of the hands or extremities

The severity of these symptoms depend on how high your thyroid levels are. 

Extremely high levels of thyroid hormone may result in severe symptoms or a condition known as Thyroid storm which is a medical emergency

It's important to realize that the presence of any of these symptoms is not normal and should be evaluated by your Doctor. 

If you or your Doctor suspects that you have hyperthyroidism you should also get thyroid function testing done at the same time (more on that above).  

These symptoms, while present, can be very alarming but they tend to subside as you are treated for your condition. 

What Triggers Elevated TSI Levels?

Graves' disease is, by definition, an autoimmune disease. 

An autoimmune disease means that your body is attacking itself due to some process which has lead to confusion of your immune system. 

Under normal conditions, your body should NOT attack itself, and it should not have a problem differentiating between foreign invaders and your own tissue. 

In autoimmune diseases, such as Graves' disease, there is a cross-reactivity between your own tissue and your immune system. 

The hallmark of Graves' disease is the presence of TSI which latch on to and activate your thyroid gland resulting in an increase in thyroid hormone in your body

But what triggers the creation of these antibodies?

What if we were able to stop the "trigger" or "prevent" it from triggering your immune system further?

As you can imagine, this is a topic which is under intense research currently because it would potentially mean a "cure" for autoimmune diseases. 

Believe it or not, our current treatment for autoimmune diseases focuses on the suppression of the immune system rather than attempting to reverse the trigger of immune dysfunction. 

But emerging research has shed light on to what may be triggering immune dysfunction. 

I've included a brief list below of known triggers of autoimmune disease (including Graves'): 

  • Increased intestinal permeability (4) - Permeability refers to how protective your intestinal lining is against bacteria and food particles. Damage may cause this lining to allow for particles to be absorbed into your body that shouldn't be there. 
  • Molecular mimicry (5) - Molecular mimicry refers to a condition in which certain bacterial capsules look similar to your own tissue. So as your body creates antibodies to fight off certain bugs these antibodies look like your own tissue and there is some cross-reactivity. 
  • Viral infections (6) 
  • Bacterial infections (7) 
  • Toxins (8) - Certain toxins can damage the immune system. 
  • Dietary considerations (9) - The foods that you eat may cause inflammation or damage to the intestinal lining and change the composition of gut bacteria. 

Do Antibodies Levels Correlate with Disease Progression?

You might expect that higher levels of thyroid stimulating immunoglobulin may correlate with a worse clinical picture. 

Meaning:

The higher your antibodies become the more likely you are to experience the symptoms of hyperthyroidism. 

Unfortunately, this doesn't always appear to be the case in every patient, but testing your antibodies frequently may be helpful in some instances. 

We know, from other studies, that at least some autoimmune disease severity does correlate with the absolute antibody level associated with that disease (10).

And some studies do show that there is a positive correlation between the severity of thyroid eye disease and the initial TSI level (11).

What does this mean?

It means that the higher your antibody level is at the time of diagnosis the more likely you are to develop thyroid eye disease. 

What is not known, however, is if your antibody level correlates with more severe symptoms of hyperthyroidism (such as heart palpitations, tremors, and so on). 

It seems that some of your thyroid tissue tends to be less responsive to TSI stimulation based on the fact that some thyroid cancers do not progress at an accelerated rate in the presence of TSI (12).

Either way, it may be in your best interest to attempt lifestyle changes which promote the reduction of these antibodies. 

Lowering Antibody Levels

We've already established that it may be worthwhile to attempt to lower your antibody level if you suffer from thyroid eye disease, but is it actually possible? 

Again, we don't have many studies focusing on this area, usually because the treatment of Graves' focuses more on medications to block thyroid function and not to block thyroid antibody production. 

Having said that, it still may be worthwhile for your attempt certain therapies to try and lower your antibodies. 

We know that certain factors can trigger the presence of autoimmune disease. 

Factors (listed above) such as increased intestinal permeability, certain nutrient deficiencies, exposure to infections and so on. 

It may be possible to "bolster" your immune system by addressing these problems. 

One of the main issues with this approach is that it is not well studied, meaning you don't know if these therapies will necessarily work for you or not. 

But, provided that the potential negative risk of the therapies does not outweigh the potential positive outcome, I see little reason why you wouldn't want to try them. 

Therapies that you may want to consider to help lower TSI levels include: 

  • Healthy diet high in fruits and vegetables and low in refined and processed foods - Eating a healthy diet can help improve the composition of bacteria in your gut, reduce inflammation and help your body naturally obtain the nutrients that it needs. 
  • Supplements such as Zinc, Vitamin D, and Selenium - Deficiencies in zinc and Vitamin D have been shown to increase your risk of developing autoimmune disease (13). Selenium has also been used to help lower antibodies in Hashimoto's thyroid disease (14) which is another autoimmune disease of the thyroid gland. 
  • Potential use of LDN (low dose naltrexone- Low dose naltrexone is a prescription medication which can be used off-label to help treat inflammatory conditions (15) and some autoimmune diseases (16). It is not well studied but some patients have experienced a reduction in their autoimmune symptoms that they attribute to the medication. It has few negative side effects, is relatively cheap (around $40 per month) and may be worth a 1-2 month trial in some patients. 

Conclusion

TSI is a lab test used to identify Graves' disease. 

It can be easily ordered in cases where hyperthyroidism is suspected based on your symptoms and it is most useful when ordered in combination with other thyroid lab tests

The presence of elevated TSI is highly predictive of Graves' disease. 

The absolute level of antibodies in your body may be useful to know because it may correlate with your risk of developing thyroid eye disease

There may also be natural ways to reduce these antibodies by targeting lifestyle therapies. 

These therapies may not work for everyone, but they are worth a shot in many patients. 

Now I want to hear from you:

Do you have elevated TSI?

Have you been able to get adequate treatment?

Have you been able to lower your levels?

What has worked for you? What hasn't?

Leave your comments or questions below! 

References (Click to Expand)

Dr. Westin Childs

Dr. Westin Childs is a Doctor of Osteopathic Medicine. He provides well-researched actionable information about hormone-related disorders and formulates supplements to treat these disorders.He is trained in Internal Medicine, Functional Medicine, and Integrative Medicine. His focus is on managing thyroid disorders, weight loss resistance, and other sex hormone imbalances.You can read more about his own personal journey here.

15 thoughts on “Thyroid Stimulating Immunoglobulin (TSI): Patient Guide to Graves’ Disease”

  1. Dr Childs, thank you SO much for your webpage with so much useful content all in one place and of course the videos. I have one nagging question that I’ve been obsessing over for days, my TSI is at 90% and your blog says “…not every single case of elevated TSI is indicative of Graves’ disease” which is consistent with what my Endo says. I used to be hyPO (not extreme case but I had many symptoms so was put on levothyroxine 100mg), after nearly a decade my TSH started to drop reaching 0.02 at one point!

    My recent blood work showed normal FT4, FT3, suppressed TSH 0.18 and, TSI – 90%, TPO <1 and TRAB .90 IU/L. As a result my Endo lowered levothyroxine. He says my blood work is not consistent with Graves (even though I have many of the symptoms). All I want to know is that it's not rare to have slightly elevated TSI and NOT be predisposition to Graves. All my research points to Graves if you have any presence in your blood. Watching your videos I'm determined to follow the dietary advice and hopefully avoid developing Graves if that is indeed possible! Thanking you so much in advance. Wish you were in Massachusetts so I could switch to your clinic!

    Kindest regards
    Marina

    • Hi Marina,

      The fact that your antibodies are elevated probably does put you at slightly higher risk for developing Graves’ when compared to the general public, but that doesn’t mean you can’t take steps (as you outlined) to try and prevent it from developing.

  2. Dr. Childs,

    Finally, helpful information on TSI! Thank you!

    My TSI is over 230. How clinically significant is a TSI of 235? Coupled with a low TSH? Is that extremely high? My conservative Endo ordered it, but then basically ignored the result.

    I have an additional question about the T3 ratio. Considering that T3 supplementation lowers TSH, would it still be recommended to go on a T3 only medication to flush out reverse T3 if TSH is already low knowing that TSH is not always the best indicator? I have had very good thyroid numbers over the last year except a low TSH and high reverse T3. My Endo keeps telling me I have hyperthyroidism, but am plagued with only hypo systems and not ONE hyper symptom ever.

    I have an ND (not my Endo) who is willing to look outside the box, but she is concerned about prescribing Cytomel because of my low TSH. For reference, I have never been treated for thyroid issues and I only sought out an Endocrinologist for postpartum thyroiditis, huge weight gain, and extreme fatigue one year ago right after I had the baby. I have high leptin (48), high night cortisol, insulin resistance, and obviously inflammation which I have been treating for the past year (diet, lifestyle, lots of supplements, Saxenda) with mild success. I have had labs done every three months since then and they are always consistent with the following:

    TSH .17
    Free T3 3.5
    Free T4 1.1
    Reverse T3 24
    TPO 1
    TRAB 15
    TSI 235

    So should one consider TSH when treating with reverse T3?

    How significant is TSI with no hyper symptoms? High TSI and low TSH really stump because I feel like a classic case of hypothyroid and it’s so frustrating!

    Any guidance would be greatly appreciated. Your reset guide has helped me tremendously!

  3. Dr. Childs,

    I also did want to ask, is it possible that I would be experiencing hyper symptoms if I was NOT suffering from leptin and insulin resistance, high cortisol, or inflammation? Are there underlying conditions that can mask Graves’ symptoms?

    I have read a little about Blocking TSH Receptor Antibodies, but I’m not understanding if or how that could be playing a role.

    I’m 14 months postpartum, I have assumed by this point thyroid numbers have “leveled” out, but I guess I don’t really know.

    I have also had an U/S (heterogeneous nonspecific lesion in the vicinity of superior pole of right lobe), a CT scan (mild focal heterogeneity at the postersuperior aspect of the right thyroid lobe…possible functioning thyroid ademona in this region) and thyroid uptake (upper limits of normal- 6 hours was 14.2% and 24 hours was 29.2%).

    I have all of these results, but nobody can really put them all together in a way that makes sense with how I’m feeling.

  4. Dr. Childs

    I have been dealing with an array of symptoms for years now. Since my kids were born I have felt so different. My 1st son was premature born at 33 weeks and my second son tried to come at 28 weeks. I suffer from anxiety, I’m almost blind in my left eye and my right eye isn’t good either. I have developed chronic dry eye , I’m very sensitive to hot and cold, I suffer from cramping and tingling in my fingers and had terrible circulation. I have very low blood pressure and experience vertigo and dizziness. I cant ride in the back seat of cars . I have terrible motion sickness. And the skin on my face is incredible dry to the point I have flakes. My mood is constantly fluctuating. I have terrible mood swings and anger. I feel trapped in my own body. I recently went to see an Endocrinologist and had testing done.
    Here are my lab results
    I was told by dr not to worry about my test and he will re test in 3 months, but I dont feel right.

    TSI 143
    T3 free 2.8
    T4 free 1.3
    THYROID PEROXIDASE ANTIBODIES<1
    FSH 3.3
    T4 (THYROXINE), TOTAL 8.6
    ESTRADIOL 40
    VItamin D 45
    TSH 0.87
    LH 3.3
    PROLACTIN 14.7

  5. Back in July I started having issues with my eyes. Swollen eyelids, large bags under my eyes, but what concerned me the most was that I was having blurred and double vision. I went to an ophthalmologist who examined my eyes and immediately asked if I had any thyroid issues, which did not. She sent me for a CT scan of my orbits because I was in a car accident in February which may have caused my eye sypmtoms; she wanted to rule out orbital fracture. The CT scan results were consistent with thyroid eye disease. I had never had any issue with my thyroid. I then went to an endocrinologist who ordered blood tests. The Results showed my TSI level was 370, but the other hormone levels were in the normal range. I am not experiencing any symptoms associated with hyperthyroidism but I’ve been told that I may develop hyperthyroidism down the road. Since my thyroid hormone levels are normal, do I actually have Grave’s disease? Is thyroid eye disease the same as Graves disease or are they separate and independent of each other? Will I definitely develop hyperthyroidism because I have such high TSI levels? I am so confused.

  6. Dr.Childs,
    Thank you SO much for your webpage with so much useful content. My Son finally was diagnosed with Graves Disease two years ago at age 16. Initially, his blood work was as followed:
    TSH <0.01 uIU/mL – WBC COUNT 6.8 K/uL
    Free T4 3.4 ng/dL – Red/blood cells 5.45 M/uL
    Hgb 13.1 g/dL – Hematocrit 40.2 %
    MCV 74 fL – RDW, RBC 13.5 % Platelet count 260 K/uL
    WHITE BLOOD CELL DIFFERENTIAL
    Neutrophils %, automated count 50 %
    Lymphocytes %, automated count 38 %
    Monos %, auto 11 %
    Eosinophils %, automated count 1 %
    Basophils %, automated count 0 %
    Neutrophils auto count 4.0 K/uL
    Ferritin 51 ng/mL
    THYROPEROXIDASE ANTIBODY TPO AB 459 IU/mL
    Thyroid stimulating immunoglobulins a/n 443 % baseline
    TRIIODOTHYRONINE (T3) T3, Total 383 ng/dL
    We have discovered that his diet made a huge difference in his numbers starch triggers it. Also caffeine and sugar. His numbers are a lot better now.

  7. I am experiencing pretty severe symptoms. My thyroid panel appears to be in “normal” range, but I have elevated monocytes and my TSI is 305.

    Any thoughts?

  8. In April 2017 I was diagnosed with Hashimoto’s Thyroiditis. My TSH was 0.0006 to 1.524
    TPO from 246 to 48
    TSI-from 6.04 ( July 2018) to 4.85
    T3 from 138 ( July 2018) to 80
    I believe it to be helping with the Thyroid Eye disease as well, but that seems to be slow going. I’m praying it will my eyes back to normal! No more heart palpitations, anxiety, digestive issues, etc…PRAISE THE LORD! 🙂 Thank you for all of your amazing Information! My Endocrinologist is in the dark as most of them are.

  9. Lab results after a recent physical showed a TSH of 0.02 and normal T3 and T4 levels. I am asymptomatic but have a TSI value of 300. While waiting for a consultation with an endocrinologist, I’ve been eating a glutin, dairy, sugar, flour and lectin free diet. I’ve also been trying to increase sleep time and meditation. I’m taking vitamin, mineral and herbal supplements along with probiotics and fermented vegetables. I’m hoping these efforts will put off frank hyperthyroidism/Graves. Any other suggestions?

    • Hi Ms. Laura,

      It sounds like you are on the right track. Unfortunately, I can’t really say exactly what you would need with such little information but I would say you are certainly heading in the right direction.

  10. Hi there,

    I am post RAI, for 10 years, 33 years old.
    TSH 0.07
    TSI 283

    I just had a positive pregnancy test. Can you please speak to the risks of the pregnancy with my TSI at that level, and why my TSI levels would be so high post-RAI? My endo has lowered my thyroid medication, but last month my TSH level did not change.

    Your help is so, so appreciated.

  11. Hi Doctor ,uptake scan in May 2016 showed toxic nodule in left lobe report :the previously demonstrated focal increased uptake in the left lobe of thyroid gland is not as avid on today’s scan (24.07.2018) rest of the thyroid gland shows homogeneous uptake no scintigraphic evidence of toxic thyroid nodule my blood test results 4 October 2018: FSH :4.1 (1.5-12.4) LH :5.7( 1.7-8.6) TSH :0.01 freet4: 17.6pmol/L freet3: 7.27 pmol/L (3.1-6.8) erythrocyte sed rate:5 mm/h (5-13) my question is my thyroid scan normal but my blood test still showing thyrotoxicosis? How this happened sir ? Scan normal blood test results still thyrotoxicosis…thanks

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