Many people have low levels of the hormones DHEA, testosterone, estrogen, and progesterone.  And while there are numerous factors which can cause low levels of these hormones, one of the biggest factors that can cause this is something known as the pregnenolone steal, also referred to as the cortisol steal.  Many doctors will recommend bioidentical hormones to correct hormone deficiencies, and while there is a time and place for hormone replacement, it of course is preferable to correct the cause of the problem whenever this is possible.  And so in this post I’m going to discuss what the pregnenolone steal is, how it can lead to deficiencies in other hormones, and what you can do to correct this problem.

I’ve spoken about the hormone pathway in some past articles and posts, but I’m going to give a little refresher here.  First of all, it’s important to understand that all of the steroid and sex hormones are derived from cholesterol.   In other words, if you have very low cholesterol levels then this alone can result in low hormone levels.  And the reason I need to emphasize this is because many medical doctors prescribe statins to a lot of their patients, and these statins can result in low cholesterol levels.  So while you don’t want cholesterol levels that are extremely high, you also don’t want to have very low cholesterol levels.

So the hormone pathway starts with cholesterol, and the hormone pregnenolone is synthesized from cholesterol.  This takes place in the mitochondria, and so if someone has mitochondrial dysfunction then this can affect the production of pregnenolone.  But assuming this isn’t the case, pregnenolone can convert into either progesterone or DHEA, and these in turn convert into other hormones.  Let’s take a look at each of these pathways:

Conversion of Pregnenolone Into DHEA.  Pregnenolone gets converted into 17-hydroxy pregnenolone by the enzyme 17α-hydroxylase.  17-hydroxy pregnenolone will in turn get converted into dehydroepiandrosterone (DHEA) by the enzyme 17,20 lyase.  DHEA is the precursor of androstenedione, which in turn is a precursor of testosterone.  Testosterone in turn can convert into estradiol via the enzyme aromatase, and dihydrotestosterone (DHT) via the enzyme 5α-reductase.

Conversion of Pregnenolone into Progesterone.   Pregnenolone converts into progesterone, which in turn gets converted into 17-hydroxy progesterone by the 17α-hydroxylase enzyme.  17-hydroxy progesterone will in turn be converted into 11-deoxycortisol, which in turn is converted into cortisol by the enzyme 11beta-hydroxylase.  17-hydroxy progesterone can also convert into androstenedione, with the help of the enzyme 17,20 lyase.  So progesterone ultimately leads to the formation of cortisol, although it can also lead to the formation of androstenedione.  Progesterone can also be converted into aldosterone, which takes place in multiple steps.

What Is The Pregnenolone Steal?

The pregnenolone steal is what happens when someone deals with prolonged chronic stress.  Out of all of the hormones I listed above, the production of cortisol is a priority.  And if someone is in a stressed out state, cortisol will be produced at the expense of DHEA.  So with the hormone pathway I discussed, you’ll recall that pregnenolone can be converted into both progesterone and DHEA, which in turn will convert into the other hormones I mentioned.  If someone is stressed out then this will inhibit the enzyme 17,20 lyase, which  helps to convert 17-OH pregnenolone into DHEA, and 17-OH progesterone into androstenedione.

So what is the consequence of this?  Well, if these enzymes are inhibited then this will result in a decrease of DHEA and androstenedione.  And remember that these hormones are precursors to testosterone, and this hormone converts into estradiol and DHT.  As a result, the pregnenolone steal can result in decreased levels of DHEA, androstenedione, testosterone, estradiol, and DHT.  Keep in mind that not all of these hormones will instantaneously become depleted, and so initially you might see some of these hormones depressed, while other hormones will look fine.

So the pathway that converts pregnenolone into progesterone will predominate.  However, cortisol is a priority over progesterone, and so progesterone will also decrease in order to produce more cortisol.  This is why this process is also referred to as the “cortisol steal” by some sources.

How Can The Pregnenolone Steal Be Diagnosed?

Sometimes it can be challenging to tell if someone is going through the pregnenolone steal, but in most cases you will see elevated cortisol levels, followed by low levels of one or more of the sex hormones.  If cortisol is high and all of the sex hormones are low or depressed, then you can be confident that the pregnenolone steal is a factor.  But wait, if someone is in postmenopause, isn’t it normal for the sex hormones to be depressed?  In other words, is it possible that if all of the sex hormones are low it’s simply due to the aging process?

Well, without question the hormones do decrease as we age.  However, this doesn’t mean that they should be depressed.  And if cortisol is elevated, then this is a pretty good sign that the pregnenolone steal is at least part of the problem.  Sure, there can always be other factors, such as one’s age, but if chronic stress is a factor then this needs to be addressed.

What are some of the symptoms someone will experience during the pregnenolone steal?  Since this involves high cortisol and low sex hormones, then the symptoms will usually correlate with this.  So for example, if someone is experiencing hot flashes or a low libido, then this probably is due to a deficiency of one or more of the sex hormones.  Other symptoms can include menstrual irregularities, anxiety or depression, vaginal dryness, insomnia, irritability, fatigue, and numerous other symptoms.  So when someone has one or more of these symptoms then it’s possible that the pregnenolone steal is the root cause of the problem.

How Can You Reverse The Pregnenolone Steal?

As for how you can halt and reverse this process, the two most important things you can do is to 1) reduce the stress in your life, and 2) improve your stress handling skills.  I realize that sometimes people can’t reduce their stress levels, but either way it is important to work on stress management.  Remember that chronic stress will inhibit the enzymes which lead to the production of DHEA, along with the androgens and estrogens.  And so if you don’t do anything to improve your stress handling skills,  then your body will continue to produce cortisol at the expense of your sex hormones.

So you need to block out time to manage the stress in your life.  I personally use a biofeedback program by the company Heart Math, as I block out 12 to 15 minutes each night before I go to bed.  Sure, I probably should be doing more than this, but it’s definitely better than nothing.  And in my opinion it’s better to spend 10 to 15 minutes EVERY DAY on stress management than 30 minutes three times per week.  Of course you don’t need to use Heart Math, as many people improve their stress handling skills through techniques such as yoga and meditation.  And there are other mind body medicine techniques as well.  I talk more about this in my article entitled “Mind Body Medicine and Thyroid Health“.

In summary, the pregnenolone steal occurs when someone is in a stressed out state.  When this is the case the body will do everything it can to produce cortisol, which in turn will inhibit the enzymes that lead to the formation of the androgens and estrogens.  So if someone has elevated cortisol levels and low sex hormones, then this is an indication that the pregnenolone steal is occurring.  And in order to halt this process you need to reduce your stress levels and improve your stress handling skills.  Some ways to accomplish this is through yoga, meditation, and biofeedback.

Just about everyone with thyroid and autoimmune thyroid conditions have some type of inflammatory process.  This is especially true with those patients with Graves’ Disease and Hashimoto’s Thyroiditis.  And while the inflammatory markers on a blood test or stool panel won’t always be positive in the presence of inflammation, I still thought it would be beneficial to discuss some of the more important markers which relate to inflammation.

Before talking about the different inflammatory markers, I’d like to briefly discuss the inflammatory process, as this will help you to better understand the purpose behind testing for these markers.  First of all, why does someone experience inflammation?  The inflammatory process occurs when someone is exposed to a trauma, infection, food allergen, toxin, or something else that puts stress on the body.  Without going into too much detail, let’s look at an example of what happens when someone is exposed to a bacterial infection. In this situation there will be an activation of white blood cells, along with the release of something called arachidonic acid.  The arachidonic acid will lead to inflammatory substances known as leukotrienes and prostaglandins, and this in turn will stimulate neutrophils, which are a type of white blood cell in your body.  In fact, when you get a complete blood count with differential one of the things it will test for is neutrophils, and if the neutrophils are elevated, then this usually indicates an acute inflammatory process.

In any case, inflammation not only results in an increase in neutrophils, but it can also cause an increase in free radicals, which causes oxidative stress and tissue damage.  And your body will also release proinflammatory cytokines, which I’ve discussed in other articles as being a factor in autoimmunity.  This process also involves something called nuclear factor kappa B (NFkB), which results in more inflammation, and one of the problems with autoimmune conditions is that NFkB gets chronically upregulated.  I spoke about NFkB in greater detail in a past blog post entitled “The Role of Cytokines In Autoimmune Thyroid Conditions”.

Hopefully you have a better understanding of the inflammatory process.  Now I’d like to go ahead and talk about the different inflammatory markers:

C-reactive protein.  C-reactive protein (CRP) is one of the main inflammatory markers commonly tested for by healthcare professionals.  It increases as interleukin 6 (IL6) is secreted by immune system cells, with an example being macrophages.  IL6 is a proinflammatory cytokine, which I’ll discuss a little later.  CRP is not a specific test.  In other words, if it is positive it means you have inflammation, but it won’t tell you where the inflammation is located.  Ideally you want the levels to be less than 1.0 mg/L, but any value greater than 3.0 mg/L doesn’t only mean that the person has a good amount of inflammation, but it also might mean that you have an increased risk of developing cardiovascular disease (1).  When getting this test it’s best to order “high sensitivity” C-Reactive protein, also known as hs-CRP.

Reference range: Most labs use a reference range of 1.0 to 3.0 mg/L, and while greater than 3.0 mg/L seems to be a cardiovascular risk, ideally you want to see this less than 1.0 mg/L.

Erythrocyte sedimentation rate (ESR).  This is another inflammatory marker commonly recommended by healthcare professionals, and this marker represents the rate at which red blood cells sediment in a one hour period.  Like CRP, an elevated ESR confirms the presence of inflammation, but it doesn’t pinpoint specifically where the inflammation is in the body.  CRP is usually preferred because these levels increase in the blood quicker after the inflammatory process begins.

Reference range: The range will vary depending on the age and gender, as most labs use a reference range less than 15 mm/hr for men under 50 years old, less than 20 mm/hr for women under 50 years old, less than 20 mm/hr for men over 50 years old, and less than 30 mm/hr for women over 50 years old (2).

Fibrinogen.  This is a protein produced by the liver, and it helps to stop bleeding through the formation of blood clots.  This marker isn’t commonly used to measure inflammation, although it frequently elevates in the presence of inflammation.

Reference range: Most labs use a reference range of 200 to 400 mg/dL

Calprotectin.  Calprotectin is a marker tested in the stool that is used to detect intestinal inflammation.  It is a calcium-binding protein that is found in large amounts in neutrophils, and during inflammation, calprotectin is released from the activated neutrophils (3).  Although you can’t use calprotectin by itself to diagnose a certain condition, it can help to differentiate between inflammatory bowel disease (i.e. Crohn’s disease and ulcerative colitis) and non-inflammatory conditions (4) (5).  It can also be used to monitor the progress of someone with inflammatory bowel disease (IBD).  Just keep in mind that calprotectin can increase with certain gut infections (which can of course cause intestinal inflammation but doesn’t necessarily mean that someone has IBD), as well as with colorectal cancer (6).  However, calprotectin is usually normal or very low in those with irritable bowel syndrome (7).  So if someone has high calprotectin then they have some type of intestinal inflammation, perhaps IBD, and most likely not IBS.  On the other hand, if someone has normal calprotectin then they probably don’t have intestinal inflammation.

It’s important to know that the intake of non-steroidal anti-inflammatory drugs (NSAIDS) increases calprotectin levels (8) (9).  Also, since intestinal inflammation is more common in those with an increased body mass index (BMI), it shouldn’t be surprising that elevated calprotectin is associated with obesity (10) (11) (12).  Although the focus here is on fecal calprotectin levels, there is evidence that serum calprotectin is increased in those with papillary thyroid carcinoma, and significantly decreases after total thyroidectomy (13).

Reference Range: The labs I’m familiar with use a reference range of less than 50 mcg/g

Lactoferrin.  Fecal lactoferrin can also be a useful marker for determining if someone has intestinal inflammation.  It is an iron-binding protein, which comes mainly from neutrophils (14).  Lactoferrin is usually significantly increased in IBD, but it can also increase with infective diarrhea, colon cancer, and after taking NSAIDS (14).  Like calprotectin, lactoferrin may also be useful in monitoring the treatment one is receiving for IBD.  And since lactoferrin is usually negative in IBS, this marker can also help to differentiate IBD from IBS (15).

Reference range: Doctor’s Data uses a reference range of less than 7.3 mcg/mL

Secretory IgA.  Secretory IgA (SIgA) is found on the mucosal surfaces of the body, and it plays an important role in providing protection by separating the outside environment from the inside of the body (16).  This is a process called immune exclusion, as it limits the entry of pathogens and antigens (16).  As a result, it is common for there to be elevated levels of secretory IgA in the presence of an infection, and sometimes a food allergen.  There is also evidence of elevated secretory IgA levels in inflammatory bowel disease (17), although it seems as if calprotectin and lactoferrin are better markers.  On the other hand, chronic stress can result in a decrease in SIgA, which in turn can increase one’s susceptibility of having an infection or an increase in intestinal permeability (18).

Reference range: The reference range seems to depend on the lab, as Doctor’s Data uses a reference range of 51-204 mg/dL, while Genova Diagnostics uses a range less than 885, with the units not specified.

Lysozyme.  Lysozyme is an enzyme that is secreted at the site of inflammation in the gastrointestinal tract.  Lysozyme levels also seem to be elevated in people with IBD (19).  One study showed that neutrophils cause elevated fecal lysozyme levels in ulcerative colitis and macrophages cause elevated serum lysozyme levels in Crohn’s disease (20).

Reference range: The labs I’m familiar with use a reference range of less than 600 ng/mL

Eosinophilic Protein X.  There is evidence that eosinophils are involved in the pathophysiology of numerous inflammatory conditions of the gut.  Eosinophils contain different proteins which are cytotoxic, and are released from the eosinophils after being activated.  One of these proteins includes eosinophil protein X (EPX).  Some suggest that EPX might be a better marker of low grade inflammation, whereas other markers such as calprotectin and lactoferrin usually don’t test positive until someone has a significant amount of intestinal inflammation.  A few studies show that EPX is positive in inflammatory bowel disease (21) (22) (23).

Reference range: Genova Diagnostics is the only lab I know of which tests for this, and they use a reference range of less than 4.6 mcg/g

Autoantibodies.  Although autoantibodies aren’t considered to be inflammatory markers, the presence of elevated autoantibodies usually correlate with an inflammatory process.  In other words, when someone has elevated autoantibodies, inflammation will also be present.  There are many different autoantibodies one can test for, but with regards to thyroid autoimmunity, the most common ones include thyroid peroxidase antibodies, thyroglobulin antibodies, and thyroid stimulating immunoglobulins.   The first two autoantibodies I mentioned are associated with Hashimoto’s Thyroiditis, while thyroid stimulating immunoglobulins are commonly found in patients with Graves’ Disease.

Reference range: These are common reference ranges for the following thyroid antibodies:

Thyroglobulin antibodies: 0-0.9 IU/mL

Thyroid peroxidase (TPO) antibodies: 0-34 IU/mL

Thyroid stimulating immunoglobulins (TSI): <140%

Proinflammatory Cytokines.  Autoimmunity involves the presence of proinflammatory cytokines, and although I don’t test the cytokines in my patients, some doctors do.  Some examples of proinflammatory cytokines that can be tested include Interleukin-1 beta (IL-1β, Interleukin-6 (IL-6), Interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α).

Which Inflammatory Markers Should You Test For?

I have most of my patients test for hs-CRP through the blood.  I don’t always test for ESR, although some healthcare professionals will test hs-CRP and ESR on all of their patients.  I do test for the thyroid antibodies in my patients.  As I mentioned earlier, I don’t do testing for cytokines.  As for calprotectin, lactoferrin, lysozyme, and some of the other stool markers, there are times when I will do stool testing on my patients, although it’s not something I do with every patient.  If someone is having a lot of gut issues and/or symptoms of inflammatory bowel disease then obtaining a stool panel might be a good idea.  However, there are functional medicine doctors who will recommend a comprehensive stool panel with every single one of their patients, and especially those with autoimmune thyroid conditions.

In summary, inflammation is a factor with just about every autoimmune condition, including Graves’ Disease and Hashimoto’s Thyroiditis.  Some of the different inflammatory markers include C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), calprotectin, lactoferrin, lysozyme, secretory IgA, Eosinophilic Protein X, and proinflammatory cytokines.  Although autoantibodies aren’t considered to be an inflammatory marker, if an autoimmune thyroid condition is suspected then it makes sense to test the thyroid antibodies.  In addition to testing the thyroid antibodies, I commonly test for hs-CRP, and while I don’t do testing for cytokines, there are times when I will recommend testing for one or more of the other inflammatory markers.

Not too long ago I attended a functional medicine conference, and the attendees were entitled to receive a free stool analysis.  Although I can’t say I enjoyed the collection process (especially since this required three different stool samples collected on different days), I was curious to see what the comprehensive stool panel results showed.  Fortunately I tested negative for pathogenic bacteria, yeast, and parasites.  And most of the other markers looked great, which of course made me very happy.  However, even though I hadn’t been experiencing any digestive symptoms, I had some positive markers for inflammation.  Fortunately the markers that are commonly high in inflammatory bowel disease looked good, although I was still surprised to see some of the other inflammatory markers on the high side.

You might wonder why I’m sharing this story with you.  Well, the main reason is to demonstrate that it is possible to have inflammation yet not experience any overt symptoms.  Another reason is to demonstrate that I’m not perfect, as while I eat a pretty good diet overall, I admittedly had been indulging more than usual prior to collecting the stool samples.  Not to make excuses, but I traveled a lot in 2015, and I probably gave in to too many temptations. And while it’s a little bit embarrassing to admit this, I thought it was a good idea to share this experience so that you realize that it’s not only a challenge to eat well when trying to restore one’s health when dealing with a thyroid or autoimmune thyroid condition, but it’s also a challenge to eat well when trying to maintain a state of wellness.

Is It Possible To Eat Too Many Healthy Foods?

When I was a teenager and young adult, there were certain foods I ate on a regular basis that I thought were healthy, but I eventually learned that this wasn’t the case.  A few examples include pasta, whole wheat bread, and soy chicken nuggets.  Of course now I have a pretty good idea of which foods are healthy and unhealthy, but one thing to be aware of is that you can eat too much of a healthy food.  For example, in the second half of 2015 there is no question that I ate too many nuts and too much dark chocolate.  Yes, I did eat some foods worse than these (i.e. pizza), and this probably was a factor as well.  But I don’t want you to overlook the fact that eating an excess of other foods that have some health benefits can also cause problems.

So was overindulging in nuts and dark chocolate a potential factor in my inflammation?  I’m honestly not sure, and I did mention earlier that I ate other foods far worse than nuts and dark chocolate.  For example, I attended my younger sister’s wedding in August of 2015, and Italian food was served.  And while we did put in a request for gluten free pasta, I ate a cannoli that definitely wasn’t gluten free.  Speaking of which, if anyone has a gluten free cannoli recipe please feel free to share it with me in the comment sections below!  I wish I can say that the cannoli was the only bad thing I ate, but the night before I also had some pizza at a Brooklyn pizzeria.  And while I ordered a gluten free pizza, I admittedly was naughty and also had some regular pizza.  Of course even gluten free pizza isn’t considered to be healthy, especially when you consider some of the ingredients used by many restaurants.  But eating pizza is even worse from a health perspective when it’s loaded with gluten (no matter how delicious it might be…and believe me, that Brooklyn pizza tasted amazing).

In last week’s blog post I spoke about gluten, and whether someone should avoid it even if they don’t feel bad upon eating it and/or don’t experience any improvement in their symptoms upon avoiding it.  I usually don’t feel bad when eating foods with gluten, but this doesn’t mean that it’s not having a negative effect on my health.  If you read last week’s blog post, you’ll recall that I mentioned that gluten apparently causes an increase in intestinal permeability (a leaky gut) in everyone, and not just those with Celiac disease or a non-autoimmune gluten sensitivity.

Do YOU Have Gut Inflammation?                                   

After reading this post, I’m sure there are some people who are wondering if they have gut inflammation.  The truth is that many people have gut inflammation and are unaware of it.  You of course can test for some general inflammatory markers through the blood such as high sensitive c-reactive protein (hs-CRP), or erythrocyte sedimentation rate (ESR).  Just keep in mind that negative findings don’t necessarily rule out inflammation.  While you can do a comprehensive stool analysis like I did, such testing can be expensive.  If you are eating gluten and/or dairy on a regular basis then this can be problematic.  But even if you are gluten and dairy free but are eating a lot of nuts, seeds, grains, and legumes, then these might cause inflammation when eaten in excess.  And so rather than spend a lot of money on additional testing, it might be best to just minimize your consumption of these foods for awhile and see if your health improves.

What’s the solution to get rid of gut inflammation?  Well, it of course depends on the cause of the inflammation.  If someone is sensitive to gluten and they eat even a small amount of it then this can result in inflammation.  On the other hand, not everyone with gut inflammation is sensitive to gluten.  In fact, some people who avoid gluten still have gut inflammation.  Other foods can cause inflammation, along with other factors such as an infection, and even chronic stress.  Taking certain nutrients and herbs can also help to reduce gut inflammation, such as fish oils, probiotics, and turmeric.  However, if the cause of the inflammation isn’t addressed then these natural anti-inflammatory agents aren’t going to be as effective.

In summary, many people have gut inflammation but are unaware of it.  And while some people with gut inflammation experience overt symptoms, this isn’t always the case.  Eating foods that contain gluten and dairy causes inflammation in a lot of people, but eating too many healthy foods such as nuts, seeds, grains, and legumes might also lead inflammation in some people.  While you can do some testing to confirm or rule out inflammation, regardless of the findings you of course want to eat a healthy diet, try not to overindulge in certain foods, and do a good job of managing your stress.

Many people with thyroid imbalances, and especially those with an autoimmune thyroid condition such as Graves’ Disease or Hashimoto’s Thyroiditis, can benefit from avoiding gluten.  It’s very common for my patients who go on a gluten free trial to tell me how much better they feel.  Sometimes the changes in their symptoms are dramatic, and some people even experience a dramatic reduction in their thyroid antibodies upon avoiding gluten.  However, not everyone feels better when avoiding gluten.  And so the goal of this blog post is to discuss what approach you should take if you don’t feel any improvement in your symptoms upon avoiding gluten.

Just as a side note, while growing up, gluten was part of my regular diet.  I would have cold cereal for breakfast (i.e. Fruit Loops, Apple Jacks, etc.).  I ate plenty of bread, cookies, and other foods loaded with gluten.  In addition, I  grew up in Queens New York, which has a bagel store on almost every corner, and there are also plenty of pizza places and bakeries.  And so I had plenty of gluten as a child and teenager, and I must admit that if gluten was as healthy as vegetables I would be eating gluten-based foods all of the time!  Sure, I feel great after having my green smoothie for breakfast, and I don’t mind eating steamed broccoli, but if bagels and pizza were just as healthy I’d be eating these foods every day.  And yes, I know there are gluten free versions of these, but they still aren’t as healthy as whole foods.

So now that you are aware of my secret obsession with bagels and pizza (more so pizza than bagels), let’s talk about what you should expect to happen when you avoid gluten.  If you are symptomatic should you experience an improvement in your symptoms within a few days or weeks of going gluten free?  Should you notice an improvement in your blood tests upon removing gluten from your diet?  It really does depend on the person, as if someone has a gluten sensitivity, or a condition such as Celiac disease, then they will usually feel better upon avoiding gluten.  However, not everyone experiences overt symptoms even when they are gluten sensitive, and some people even have silent Celiac disease (1) (2) (3).  Admittedly most of the cases of silent Celiac disease seem to be present in children and adolescents, but adults can have this as well.

How Can You Tell If You Have A Gluten Sensitivity?

There are basically two ways to tell if someone has a gluten sensitivity…by symptoms or through testing.  Of course if you experience symptoms when eating gluten then this is a clear sign to avoid it.  The problem is that not everyone experiences overt symptoms when consuming gluten, and so the lack of symptoms when consuming gluten doesn’t necessarily rule out a gluten sensitivity.  Also, keep in mind that foods that contain gluten are typically high in FODMAPs, and so if you have problems with gluten and other high FODMAP foods then there is a chance that gluten sensitivity isn’t the issue, but you might have small intestinal bacterial overgrowth instead.  If you aren’t familiar with FODMAPs then I would read the blog post I wrote entitled “Should People With Thyroid Conditions Follow a Low FODMAP Diet?”

As for testing, while this can help to detect a gluten sensitivity problem, a negative finding doesn’t rule out a sensitivity to gluten.  For example, if someone gets a Celiac panel which measures the antibodies to gliadin and transglutaminase and the test results are negative, this doesn’t mean you can’t be sensitive to other proteins of gluten which aren’t tested.  Cyrex Labs has the most comprehensive test for gluten that I know of, but while it tests for many of the markers of gluten, it doesn’t test for all of them. In addition, if someone has depressed immunoglobulins then this can result in a false negative result.

So hopefully you realize that it can be challenging at times to determine if someone has a gluten sensitivity, as while a positive test result usually confirms a gluten sensitivity, a negative result doesn’t necessarily rule out problems with gluten.  If one has overt symptoms when consuming gluten and/or tests positive for a gluten sensitivity then there is no question that they should avoid gluten.  But if they don’t experience negative symptoms, and if the testing reveals no gluten sensitivity, then it’s not clear if they should avoid gluten.  And this is one reason why many healthcare professionals will have all of their patients who have a chronic health condition avoid gluten.

“Can I Get Into Remission If I Continue To Eat Some Gluten?”            

At this point you might still be wondering if you can restore your health if you continue to eat gluten.  The answer is “maybe”.  In my experience it is possible for some people with Graves’ Disease and Hashimoto’s Thyroiditis to restore their health, even if they don’t completely avoid gluten.  While some natural healthcare professionals will disagree with this, and while I do encourage my patients to avoid gluten while following a natural treatment protocol, I have had some patients continue to eat gluten and still get into remission.  This doesn’t mean that they were eating large amounts of whole wheat bread and pasta on a daily basis, as they were still eating very healthy, but they didn’t completely avoid all sources of gluten.

With that being said, it does appear that gliadin, which is one of the proteins in gluten, causes an increase in intestinal permeability in everyone, even those who aren’t sensitive to gluten (4).  What this means is that gluten causes a leaky gut in everyone.  And while this study did show that those people with active Celiac disease and a non-autoimmune gluten sensitivity had a greater increase in intestinal permeability, those who didn’t have Celiac disease or a non-autoimmune gluten sensitivity still experienced negative effects on the intestinal barrier when consuming gluten.

However, some people are hesitant to avoid gluten if they don’t feel worse upon eating it, or if they don’t notice any positive changes in their symptoms upon eliminating it.  The problem is that you can’t always go by symptoms alone, and it is impossible to predict who will do fine when continuing to consume gluten.  And so there are basically two options for those who are looking to restore their health, yet don’t experience any negative symptoms when eating gluten (or don’t feel better upon eliminating it).  One option is to continue to eat gluten while following a natural treatment protocol and see how you progress.  If you choose this option I still would try to minimize your consumption of gluten, and if you are eating mostly whole foods then it’s easy to accomplish this.

A second option is to play it safe and completely avoid gluten.  This always leads to questions such as “is it okay to have a tiny amount of gluten?”, or “what if I’m 99% gluten free?”  This once again depends on the person.  Some people make an effort to go gluten free, but either intentionally or accidentally get exposed to small amounts of gluten.  And if they don’t have Celiac disease or a non-autoimmune gluten sensitivity then they probably will do fine.  On the other hand, if they have a gluten sensitivity they will continue to have gut inflammation even when consuming small amounts of gluten, and as a result they probably won’t improve.

What Should You Do If Avoiding Gluten For A Prolonged Period Of Time Doesn’t Help?

I’ve come across people who have gone gluten free for six months or longer without any improvement in their symptoms or thyroid blood tests/antibodies.  Isn’t this an obvious sign that they aren’t gluten sensitive?  Well, when this is the case there is a good chance that gluten isn’t the primary trigger.  However, keep in mind that there can be multiple triggers.  For example, someone can have a gluten sensitivity that is causing inflammation, but the main trigger is an underlying infection.  And so avoiding gluten might have helped with the inflammation, but since the main trigger (the infection) was still present, the person didn’t notice much of a difference with their symptoms when avoiding gluten.

It’s a no-win situation, and so you might as well just throw in the towel and munch on some donuts or muffins, right?  The truth is that I’m not against some people eating gluten on an occasional basis…after they have restored their health back to normal.  Although I try to eat a healthy diet most of the time, I’d be lying if I told you that I was completely gluten free 100% of the time.  Gluten should admittedly be avoided, just like alcohol, and while I don’t drink alcohol, I do occasionally indulge in foods that contain gluten.  I’m not suggesting that everyone is able to eat gluten after they restore their health, as there definitely are people who need to completely avoid it.  And next week I’ll be releasing a blog post which might suggest that I should completely avoid gluten altogether, even though I feel fine when I consume it.

In summary, while many people feel better upon avoiding gluten, not everyone who eliminates gluten from their diet notices an improvement in their symptoms and blood tests.  When this is the case, it is tempting to want to go ahead and eat gluten on a regular basis, but just remember that the lack of symptoms, and even a negative test result doesn’t rule out a gluten sensitivity.  While some people might be fine eating small amounts of gluten while trying to restore their health, others won’t do well.  As a result, I think it’s a good idea for everyone to go on a gluten free trial, although this doesn’t mean that everyone needs to completely avoid gluten on a permanent basis.

Thyroxine, also known as T4, is the primary thyroid hormone secreted by the thyroid gland.  This hormone is low or depressed in those people with hypothyroidism, and it is usually elevated in those with hyperthyroidism.  Although the focus of this post will be on T4, triiodothyronine (T3) is another thyroid hormone.  And because most T3 is produced via the conversion of T4 into T3, if someone has low T4 levels then they usually will have low T3 levels, although there are exceptions.

Before talking about some of the factors which can cause low T4 levels, I’d like to briefly discuss how thyroid hormone is manufactured.  Because if you understand how it is formed then you will also understand some of the things which can lead to lower thyroid hormone levels.  The thyroid follicles are cells in the thyroid gland, and this is where thyroid hormones are produced.  You get iodide from the diet, which travels through the bloodstream to the thyroid follicular cells, which in turn takes up the iodide with the help of something called a sodium-iodide-symporter.  Thyroid peroxidase is an enzyme which plays an important role in iodination, which involves the oxidation of iodide ions to form iodine atoms.

Thyroxine contains four iodine atoms, which is why it’s referred to as “T4”, and these iodine atoms attach to a tyrosine molecule.   And as you might have guessed, triiodothyronine contains three iodine atoms, which is why it’s referred to as “T3”.  There is also thyroglobulin, which is synthesized by the thyroid follicular cells, and this acts as a substrate for the synthesis of T3 and T4, and also stores inactive forms of thyroid hormone.  So what’s important to understand is that iodine and tyrosine are important for the formation of thyroid hormone, and thyroid peroxidase and thyroglobulin also play important roles.

Hopefully you have a better understanding of how thyroid hormone is formed.  Now I’d like to go ahead and look at seven reasons why you might have low T4 levels:

1. Hashimoto’s Thyroiditis.  This is an autoimmune condition which involves the immune system attacking the thyroid gland.  The immune system specifically attacks thyroglobulin and/or thyroid peroxidase, which in turn is what results in low or depressed thyroid hormone levels.  Although many people with Hashimoto’s don’t have low T4 levels, since most medical doctors don’t do anything to address the autoimmune component, the immune system will continue damaging these structures of the thyroid gland, and as a result, over a prolonged period of time most patients with Hashimoto’s will eventually have low T4 levels.

What’s The Solution To This Problem?  The goal is to address the autoimmune response.  The most important factor is to try to detect and then remove the autoimmune trigger.  While doing this you should do things to reduce inflammation and increase regulatory T cells, which I discussed in a separate blog post entitled “Regulatory T Cells and Thyroid Autoimmunity“.

2. Iodine Deficiency.  Since iodine is necessary for the formation of thyroid hormone, it should come as no surprise that an iodine deficiency can result in low T4 levels.  But how can you determine if you have an iodine deficiency?  The most accurate way of testing for iodine seems to be in the urine.

What’s The Solution To This Problem?  If someone has an iodine deficiency then the obvious goal should be to correct it.  However, not everyone does well when taking iodine, especially many people with Hashimoto’s Thyroiditis, and so if you test positive for an iodine deficiency and are thinking about supplementing with iodine, you do need to be cautious.  This is especially true if you are thinking about taking high doses of iodine, but it can also be a problem in some people even in small doses.  For those people with Hashimoto’s, many times it is best to restore the health of the immune system before taking iodine.

3. Dysregulation of the HPT Axis.  When talking about the formation of thyroid hormone earlier, I didn’t talk about the role of the hypothalamus and pituitary gland.  These both play an important role in the signaling of thyroid hormone.  Most people are familiar with thyroid stimulating hormone, which is also known as TSH.  TSH is released by the pituitary gland, which tells the thyroid gland to produce more thyroid hormone.  However, the hypothalamus communicates with the pituitary gland, and so if there are problems with either the hypothalamus or pituitary gland then this in turn can cause problems with the thyroid gland.

What’s The Solution To This Problem?  If someone has dysregulation of the hypothalamic-pituitary-thyroid (HPT) axis, then the goal should be to improve the health of the HPT axis.  Adaptogenic herbs can help to accomplish this, with ashwagandha perhaps the most well known herb which can have a positive effect on the HPT axis.  Taking glandulars to support the hypothalamus and pituitary gland can also help in some cases.  However, while taking adaptogenic herbs can help, stress causes dysregulation of the HPT axis, as well as the hypothalamic-pituitary-adrenal (HPA) axis, and so improving your stress handling skills is essential.

4. Tyrosine Deficiency.  You learned earlier that tyrosine plays an important role in thyroid hormone production, as the iodine atoms attach to a tyrosine molecule.  And while most cases of low T4 levels aren’t caused by a tyrosine deficiency, it’s still something to consider.  I spoke about this in greater detail in an article I wrote entitled “Tyrosine and Thyroid Health“.

What ‘s The Solution To This Problem?  If someone does have a tyrosine deficiency then they will want to increase their consumption of tyrosine-rich foods such as chicken, turkey, fish, eggs, avocados, and spinach.  Taking a tyrosine supplement might also be a good idea if one has a deficiency..

5. Iron deficiency.  As you have learned, the enzyme thyroid peroxidase plays an important role in thyroid hormone formation.  Thyroid peroxidase is a heme-containing enzyme, which means that it is dependent on iron.  And the research shows that an iron deficiency can reduce thyroid peroxidase activity, which in turn can affect thyroid metabolism (1) (2).

What’s The Solution To This Problem?  Many people are deficient in iron, and so before ruling out an iron deficiency you want to make sure to get  a complete iron panel consisting of serum iron, ferritin, iron saturation, and TIBC.  If you have an iron deficiency then supplementation probably is a good idea.  However, you also want to try addressing the cause of the problem, which I spoke about in an article entitled “Iron Deficiency Anemia and Thyroid Health“.

6. Environmental toxins.  Certain environmental toxins can potentially inhibit thyroid activity.  Numerous studies show that xenoestrogens such as BPA and flame retardants can inhibit thyroid hormone production (3) (4) (5).  Other studies also show that fluoride can interfere with thyroid gland function (6) (7).  Bromide might also have an inhibitory effect on thyroid hormone (8).  Perchlorate inhibits the uptake of iodine and can decrease thyroid hormone production (9).  Heavy metals such as mercury can also inhibit thyroid hormone production (10) (11).

What’s The Solution To This Problem?  Although it’s impossible to eliminate your exposure to environmental toxins, you of course can do things to minimize your exposure to them.  For example, you want to avoid drinking bottled water on a frequent basis, reduce your exposure to flame retardants, along with fluoride, and other environmental toxins.

7. Soy and other goitrogenic foods.  This one is controversial, as while there are studies which show that soy phytoestrogens can cause hypothyroidism (12), other studies show that this isn’t the case (13).  Other studies suggest that soy only has antithyroid effects in the presence of an iodine deficiency (14).  With regards to other goitrogenic foods (i.e. cruciferous vegetables, spinach, strawberries, etc.), there are no human studies I’m aware of which show that eating these foods inhibit thyroid activity.

What’s The Solution To This Problem?  Besides the possibility that soy has goitrogenic properties, soy is a common allergen, and most soy is also genetic modified.  And so it might be best to minimize your consumption of soy.  With that being said, some people are able to eat some organic fermented soy without a problem, although not everyone.  As for other goitrogenic foods, such as cruciferous vegetables, most people are able to eat these without a problem, although if someone has a moderate to severe iodine deficiency then it might be best to play it safe and limit your consumption of these foods.  However, keep in mind that cooking these foods will also reduce the goitrogenic activity.

In summary, there are numerous factors which can cause low T4 levels.  Hashimoto’s Thyroiditis is the primary cause of hypothyroidism.  Nutrient deficiencies can also play a role, including iodine, iron and tyrosine.  Other potential causes include dysregulation of the HPT axis, certain environmental toxins, and perhaps certain goitrogenic foods.