In the last post I discussed some of the basics of autoimmunity, including why some people develop specific autoimmune conditions such as Graves’ Disease and Hashimoto’s. I also discussed the role of human leukocyte antigen (HLA) in autoimmunity, as well as the importance of regulatory T cells in preventing autoimmunity. In this post I will discuss the autoimmunity timeline, which will help you to better understand the different stages of thyroid autoimmunity.
If you read the last post then you probably understand that in order for autoimmunity to develop, a combination of genetic and environmental factors are necessary. However, having a genetic surface marker and being exposed to an environmental trigger usually isn’t enough to lead to an autoimmune condition. If this were true, then many more people would develop autoimmunity, as many people with these genetic markers are exposed to one or more environmental triggers, yet don’t develop an autoimmune condition. And so other factors are necessary, such as a decrease in regulatory T cells, and perhaps an increase in intestinal permeability (a leaky gut). Healthy mitochondria are also important, as several mitochondrial proteins have been implicated as regulators of apoptosis in the immune system that are required for prevention of autoimmunity (1) . I’m sure there are other factors as well which we’re unaware of at this time.
Understanding The Autoimmunity Timeline
But in addition to understanding what factors can lead to the development of an autoimmune thyroid condition such as Graves’ Disease or Hashimoto’s Thyroiditis, it is also beneficial to understand the autoimmunity timeline. After all, most chronic health conditions take many years to develop. And then when they do develop, it can take many more years for symptoms to manifest. So let’s go ahead and look at different stages of autoimmunity:
Stage #1: Pre-autoimmunity. This is the most critical time to prevent an autoimmune condition from developing. As I mentioned numerous times in the last post, having a genetic marker and being exposed to an environmental trigger usually won’t cause an autoimmune condition without other factors being present. I mentioned a decrease in regulatory T cells as being a factor. A leaky gut can also be a factor in some, if not all autoimmune conditions. Mitochondrial dysfunction can also be a factor. But it usually takes years for people to develop a significant decrease in regulatory T cells, a leaky gut, or mitochondrial dysfunction.
So the goal in most people should be to do whatever is necessary to have a healthy immune system, a healthy gut, and healthy mitochondria. Obviously there is a lot of overlap, as someone can’t have a healthy immune system without having a healthy gut. And one also needs healthy mitochondria to have a healthy immune system. Of course there are many factors which can have a negative effect on the these areas, such eating a poor diet with a lot of refined foods and sugars, consuming common allergens such as gluten and dairy, being exposed to prolonged chronic stress, getting insufficient sleep for many months or years, toxic overload, an acute or chronic infection, etc.
As you can see, there are a lot of different factors which can set the stage for autoimmunity. Keep in mind that in most cases, if someone has a genetic marker for an autoimmune condition, a SINGLE exposure to an environmental trigger isn’t going to cause autoimmunity. After all, most people deal with chronic stress these days, everyone is exposed to toxins, etc. However, if someone is FREQUENTLY exposed to one of more of these factors, then over time this can cause a decrease in regulatory T cells, lead to a leaky gut, and/or cause mitochondrial dysfunction, and set the stage for autoimmunity. So perhaps the best way to think of it is that we’re all exposed to one or more of these triggers, but it’s the frequent exposure to these triggers over time which increases the likelihood of someone developing an autoimmune condition.
Stage #2: Silent autoimmunity. In this stage, autoimmunity has already been triggered. However, there has been very little or no tissue damage, and therefore no symptoms are present, and the blood test results are negative at this point (i.e. normal TSH and thyroid hormone levels). This is what happens with pretty much all autoimmune conditions. However, the duration of this stage will vary greatly depending on the autoimmune condition. For example, if someone has elevated thyroglobulin antibodies, which are associated with Hashimoto’s Thyroiditis, then there is a good chance that these will cause damage to the thyroid gland. And if nothing is done to address the autoimmune component then the damage can be so extensive that the person might reach the point where they need to take thyroid hormone medication.
However, the person with Hashimoto’s Thyroiditis can be in the “silent” phase for many years. With Graves’ Disease it may be a different story, as my guess is that the silent phase isn’t nearly as long. And the reason for this is because when dealing with autoimmune conditions which involve tissue damage (i.e. Hashimoto’s, multiple sclerosis), the tissue damage can be minimal for many years, and so in some cases it can take a long time for the person to develop symptoms, which I’ll discuss next in phase #3. Graves’ Disease is different from many other autoimmune conditions in that it doesn’t necessarily involve tissue damage. The TSH receptor antibodies don’t seem to damage the TSH receptors, but apparently stimulate them, which results in the release of thyroid hormone. And the symptoms of Graves’ Disease are usually more noticeable initially than those of many other autoimmune conditions. Although in some cases it might take many years between the time someone develops Graves’ Disease autoantibodies and the time they develop hyperthyroid symptoms, in my opinion this is less likely to happen.
Stage #3. Symptoms present with some tissue loss. Although stage #2 might involve some tissue damage, it’s very minimal, and it’s in stage #3 where this damage reaches the point where the person begins to experience symptoms. Once again, it can take many years for this to happen. So with the person who has Hashimoto’s Thyroiditis, what frequently will happen is that due to the tissue damage to the thyroid gland, the person will begin to experience some symptoms. As a result, they might visit their medical doctor, who will run a thyroid panel, and at this point the TSH might be elevated, or it still might look fine. Obviously one can’t rely on the TSH alone, but unfortunately this still is what frequently happens at many medical doctor’s offices. And if the TSH is within the lab reference range, regardless of how the person feels, they might be told that everything is fine since the tests are within the normal reference range. On the other hand, a smart doctor will run a more comprehensive panel which not only evaluates the thyroid hormone levels (which probably will also be normal), but they will also look at the thyroid antibodies, in this case thyroperoxidase antibodies and thyroglobulin antibodies.
Unlike Hashimoto’s Thyroiditis, when someone with Graves’ Disease is experiencing symptoms there usually is a correlation with the blood test results. So for example, if someone has elevated TSH receptor antibodies and begins experiencing hyperthyroid symptoms (i.e. increased pulse rate, heart palpitations, tremors, etc.) then there is a good chance the TSH will be depressed and/or the thyroid hormone levels will be elevated, although this isn’t always the case. As I’ve mentioned in other articles and posts, for some people with Hashimoto’s Thyroiditis and Graves’ Disease, the thyroid antibodies will show up as being negative when doing a blood test.
Stage #4. Symptoms are present and there is greater tissue loss. This is the “final” stage of autoimmunity, as it’s when the person’s symptoms will usually worsen, there will be greater tissue loss, and the blood tests will be positive. Although some people might be diagnosed with an autoimmune thyroid condition in stage #3, especially those with Graves’ Disease, many people with Hashimoto’s Thyroiditis won’t be diagnosed until they reach stage #4. And the reason is because most of the symptoms of Hashimoto’s Thyroiditis can’t be measured. In other words, if someone with Hashimoto’s Thyroiditis is in stage #3 and presents with negative blood tests, yet they are experiencing symptoms such as fatigue, brain fog, and hair loss, these symptoms can’t be measured. On the other hand, if someone with Graves’ Disease is in stage #3 they very well might have an elevated heart rate, which will be detected almost immediately when the vital signs are being taken. Getting back to Hashimoto’s Thyroiditis, if someone is in stage #3 and has negative blood tests, often times doing a good case history and conducting a thorough physical exam can determine if someone has a thyroid condition. But this isn’t always the case, and unfortunately, many medical doctors see such a high volume of patients that they won’t perform a thorough physical exam if all of the tests look good.
In summary, different autoimmune conditions are characterized by different types of autoantibodies. There are a few factors which will determine whether autoimmunity will develop, as a genetic marker is usually present, and an environmental trigger is also necessary. However, other factors are usually necessary to set the stage for autoimmunity, such as a decrease in regulatory T cells, a leaky gut, and/or mitochondrial dysfunction. So in order to prevent autoimmunity, or restore the health of someone who already has an autoimmune condition it would appear to be necessary to have high numbers of regulatory T cells, a healthy gut, and healthy mitochondria. I also discussed the four stages of autoimmunity, which should also help you to understand the progression of most autoimmune conditions.