Hashimoto’s Part 2: Causes of Autoimmunity

Person rubbing their neck.Hashimoto’s thyroiditis is one of over 100 autoimmune conditions, and in general there are 3 primary causes of autoimmunity.  As I discussed in Part 1, Hashimoto’s involves the thyroid gland, but it is actually caused by a problem with the immune system. 

When we manage Hashimoto’s in any medical model, we start with treating the thyroid and decreasing symptoms. Thyroid medications can do this for 75-80% of people, but may not be halting the autoimmune process.   

To truly address the causes of autoimmunity, we have to address the immune system.  This involves what I call “full spectrum” functional medicine, which considers the potential triggers and drivers that lead to activation of the immune system (in particular, the Th17 cells – but I won’t go into that in this article!).  Patients that seek this approach, or are still having symptoms despite “normal” looking labs, are the ones with whom I typically work.



Diagnosis: Hashimoto’s is diagnosed when someone has high antibody levels on a blood test, or has a thyroid ultrasound and/or thyroid biopsy that indicates thyroid damage attributed to an autoimmune process. 

Symptoms: Many with Hashimoto’s will have hypothyroid-like symptoms (see Part 1 for a list of common symptoms), but when thyroid cells are destroyed, thyroid hormones that are in these cells are released into the bloodstream (which can cause periods of hyperthyroid symptoms).   

Treatment: The primary treatment of Hashimoto’s, in both mainstream medicine and in functional medicine, involves the use of prescription thyroid hormones.  By the time someone has symptoms, up to half of the thyroid can be destroyed, so many people require these prescriptions to compensate for this loss.

Treatment to autoimmune remission (rarely done via a mainstream medicine approach): When we start to address treatment of Hashimoto’s beyond balance of the thyroid hormones, we use antibody levels on a blood test to guide us on efficacy.  But we have to do this the right way:

  1. Don’t over-test: I recommend only testing antibodies every 3-6 months (due to biology, noted below).
  2. Don’t forget basic biology: Any treatment or intervention that is initiated should be followed for at least 3 months.  Why?  All antibodies for thyroid disease are part of a class of molecules known as IgG immunoglobulins.  On average, these molecules will be active for at least 6 weeks (if they are not bound to something in the body).  However, when these bind to something, they can stay around for months.



There is not a single cause for Hashimoto’s.

Any complex illness like an autoimmune condition will have multiple causes.  And these will be unique to the patient.

There are many books, blogs, forums, and more that touch on the research behind autoimmunity.  And there is a LOT of scientific research on this topic!  However, I often advise my patients (and colleagues) to focus on the top 3 likely causes that apply to the patient rather than evaluate and test for all.  This keeps costs down and is the smartest way to practice functional medicine (in my experience).

To understand the development of Hashimoto’s, we start with what Dr. Alessio Fasano termed the “triad of autoimmunity”.


It is well-known that genetics and environmental elements are involved in triggering autoimmunity.  Mainstream medicine and functional medicine can agree on that.

But functional medicine addresses these and one other factor, which is in part based off the work of Dr. Alessio Fasano (who is a gastroenterologist, researcher, and professor at Harvard Medical School – in addition to a whole host of other positions).  He is actually responsible for developing one of the first tests that we continue to use to identify Celiac Disease (tTG test)!

In 2000, Dr. Fasano and his team discovered a protein called zonulin that is released in response to an environmental trigger.  It is found in high amounts in those with conditions such as Type 1 Diabetes, Rheumatoid Arthritis, Celiac Disease, irritable bowel syndrome, and more.

Dr. Fasano tested zonulin for years before publishing his findings and autoimmune theory in Scientific American in 2009 (when he used the term the autoimmune “triad”).  I encourage you to read about his story via an interview here!

The 3 factors that make up the triad (aka the causes of autoimmunity) include:

  1. Genetic predisposition
  2. Environmental triggers
  3. Hyper-permeable gut lining

To understand how zonulin works, think of it this way.  The gut barrier is like a piece of tightly woven fabric.  It stretches (aka “weakens”) to expose the gut contents to a part of the immune system known as the GALT.  Zonulin is one molecule that causes this stretching, to essentially open the “gaits” between the gut and the GALT.  But the GALT also tests what is in the gut by reaching through the gut lining without stretching it, which is preferred over the stretching mechanism. This “stretching” is a normal process that serves to communicate with the immune system in order to protect the body from potential dangers. 

But when higher amounts of zonulin are present, it is because too much of the gut lining is being stretched/weakened.  This leads to the GALT being exposed to larger particles, resulting in a chronically activated immune response and eventually autoimmunity.

Let’s address each of these factors.



The best way to evaluate genetic potential is by doing a thorough family history. Genetic predisposition only contributes to 30% of the autoimmune process, and genes can be turned on/off by environmental factors. 

Genetic testing is still evolving, and can be expensive.  Thankfully, we have a lot of companies doing more research in this area.  However, I personally do not utilize a lot of genetic testing for autoimmunity in my practice (I used to do research for a genetics company, and realized how much we really don’t know – especially when you start looking at adjacent genes that can turn on or off the genes that are of concern!).  Thus, at this time, I find it more clinically useful for me to look at the environment than it is for me to look into the genes. 

“Genes load the gun; environment pulls the trigger”



These are unique to everyone. 

For example, inflammation can be beneficial in small amounts.  We know that gluten cause some inflammation whenever anyone consumes it.  Some people will sequester the inflammation quickly, without leading to long-term problems.  But others will become intolerant to the inflammation, resulting in symptoms and chronic conditions. 

The same is true for other factors.  Unless we live isolated in a bubble, we will always be exposed to factors with which the body has to eliminate.  Some people will “detoxify” these elements effectively, and others will not.  These factors include physical byproducts of chronic stress (yes, stress does cause physical changes in the body!), indoor mold toxins (aka mycotoxins), chemical exposures (e.g. pesticides in non-organic foods), heavy metals from food or dental procedures, elements found in tap/bottled water, and more.

So, as we can see, there are a plethora of potential environmental triggers.  In its basic definition, environmental encompasses the air we breathe, the food we eat, the water we drink, the lifestyle we lead, our relationships, and more.

The following is a list of triggers that I start with, when I approach autoimmunity.  As I consider each of these in my patients, I am also addressing specific immune cells (e.g. Th1, Th17, Th2, and Treg cells),  in order to bring balance to the immune system so it can do its job better.  More than half of these can be evaluated with asking the right questions, and using blood testing.  If needed, I will consider additional testing methods (like stool testing, urine-based tests, and more).

  • Nutrition imbalances (e.g. nutrient deficiencies, too many inflammatory foods, foods that trigger an immune response, etc).
  • Chronic stress (these can be physical, emotional, negative thoughts, etc).
  • Byproducts from environmental elements like indoor mold (mycotoxins)
  • Build up of heavy metals like aluminum and mercury
  • Reactivated viruses like the “mono” virus (aka EBV; click here for an entire article I wrote on this)
  • Subacute bacterial or parasitic infections (e.g. dysbiosis in the gut, SIBO, blastocystis hominis)
  • Hormone imbalances (e.g. cortisol, reproductive hormones, insulin, vitamin D)

Before you feel overwhelmed, it is important to note that you don’t need to test for everything.  In fact, you may be able to avoid seeing me or another functional medicine practitioner just by optimizing the labs I mentioned in Part 1 (which can be ordered by your primary care practitioner) , completing an online program like the “SAD to AIP”, Izabella Wentz’ book that provides a 90-day self-care protocol for Hashimoto’s, or purchasing my friend Sarah Ballantyne’s book on using nutrition to reverse autoimmunity!  These resources address the lifestyle habits and daily exposures that are the primary drivers of autoimmunity.



“Leaky gut” is actually not a true disease process, since we could not absorb our food/liquids without some gut permeability.  Because it is not a legitimate diagnosis, mainstream medical practitioners will often dismiss the existence of this.  I use this term for simplicity purposes (just like I may say someone had a “heart attack” instead of using the term “myocardial infarction”), since it is easier to say than “pathologic small intestine hyper-permeability”!

I touched on some of the mechanism behind leaky gut when discussing zonulin above.  To understand more of what triggers this process, we must remember the role of the gut. 

In general, our gut has 3 purposes:

  1. Break down food into smaller particles (chewing, stomach acid, enzymes)
  2. Kill “bugs” (stomach acid)
  3. Absorb nutrients and molecules of energy (if broken down properly)

Most of the time, our body is able to compensate for things that impact the above processes (e.g. not chewing our food well enough, taking an acid-blocker for reflux, etc).  But if any of those processes are chronically inadequate, we may see nutrient deficiencies, bacterial overgrowth…and “leaky gut”. 

To decrease gut hyper-permeability and immune activation, we have to start with what is triggering the gut to become hyper-permeable.  I won’t misguide you – to restore the gut lining takes work!  It often involves changing food choices, taking therapeutic supplements, changing mindset, changing habits, and addressing the most neglected and forgotten treatment – developing a daily habit that decreases the response to stress (stress releases cortisol, and cortisol triggers “leaky gut”).

I’ll address more of the treatment of this in the next part of this series, but I want to touch on how we evaluate whether this is present or not.

First, if someone has active autoimmunity, with or without gut symptoms, I don’t believe we have to test for this

Second, if I do test for this, it is either because a patient wants the test, or we’ve already done a lot of health optimization but haven’t reached 80% improvement in symptoms and resiliency (which is my goal with all patients).

So, what test can we use to look for this? 

Unfortunately, we can’t test for this with national labs, used by mainstream medical practitioners. Independent labs are the best options right now, and these may or may not work with insurance companies.  But we have to consider what is being tested for.

When the zonulin molecule was first discovered, testing was focused on the presence or absence of the zonulin molecules.  As we’ve learned more about it, we now know that zonulin is short lived in the bloodstream (which doesn’t make it a reliable molecule to test) and it fluctuates throughout the day.  But we can test for antibodies to this.  Thus, if we test for “leaky gut”, the test that is most valid looks for zonulin antibodies.  Right now, I only trust one lab (Cyrex Labs), and it costs around $200.



  • Hashimoto’s is one of over 100 autoimmune conditions
  • There is no single cause of Hashimoto’s
  • Always start with treating the thyroid and managing symptoms with medication(s)
  • Use full spectrum functional medicine to address immune triggers
  • Follow testing of thyroid antibodies to determine the activity of autoimmunity.  The goal is to see progressive lowering over time (not to necessarily get these to normal or zero).
  • The “triad of autoimmunity” is our best hypothesis and guide for addressing any autoimmune condition
  • The goal is not to identify and eliminate every potential cause or trigger, but to re-establish normal immune function.  Our bodies are smart, but they sometimes needs to be re-directed. 

We each have a unique ability to tolerate external factors from our environment.  If you are dealing with the ups and downs of Hashimoto’s or any autoimmune condition, give your body grace.  It is doing what it knows to do.  There is no cure, but we can put autoimmunity into remission and learn how to deal with flares when they occur! 

The information above applies not only to Hashimoto’s, but also to Multiple Sclerosis, Grave’s Disease, atherosclerosis (which is associated with high cholesterol and heart disease), rheumatoid arthritis, and more.

If you are interested in working with me, starting in January 2021 I am joining the amazing team at Parsley Health and am accepting new patients!

Thank you for taking the time to read this article.  I hope it brings some clarity and direction to you or a loved one.

Meg McElroy MS, PA-C

The information contained in this article is for educational purposes only.  It does not constitute a diagnosis or prescription for treatment.