A Different View on a Common Autoimmune Disease, Hashimoto’s Thyroiditis

A Different View on a Common Autoimmune Disease, Hashimoto's Thyroiditis

I read this paper published in Naturopathic Currents an evidence-based publication for the Naturopathic profession in April 2014. The author Dr. Fiona McCulloch wrote a review of the most current research on the autoimmune condition Hashimoto’s Thyroiditis. I was fascinated and reached out to Dr. McCulloch about her findings.

Thank you to Naturopathic Currents and Dr. Fiona McCulloch for permission to repost it here at Hypothyroid Mom.

Written by Fiona McCulloch ND, White Lotus Integrative Medicine

I’ve written this paper to review current information on a common autoimmune condition, Hashimoto’s Disease – this is by far the most common autoimmune disease I treat in my practice. Natural treatments for Hashimoto’s Thyroiditis will be discussed, and I’ll also include a unique functional medicine view of how the condition may develop. This information is based on the most recent research into autoimmune disease, and since this field is consistently evolving, we expect that this information will change in time.

Hashimoto’s thyroiditis is an autoimmune disease that is characterized by an infiltration and destruction of the thyroid gland by the immune system. In this condition, immune cells produce antibodies against a key enzyme that is required for thyroid hormone production — thyroid peroxidase — and/or against thyroglobulin, which is the building block of thyroid hormones.[1. Dayan, C.M. and G.H. Daniels GH. “Chronic autoimmune thyroiditis”. N Engl J Med. Vol. 335, No. 2 (1996): 99-107]

Hashimoto’s is believed to be the most common cause of hypothyroidism in North America, and is among the most common causes of goiter in areas of the world where iodine intake is considered sufficient.[2. Kumar, V. The Endocrine System. Robbins and Cotran Pathologic Mechanisms of Disease, 8th ed. Philadelphia, PA: Elsevier, 2010: 1111–1205] An average of 1.5 out of 1000 people have this disease, it is 7 times more common in women than in men, and is most prevalent in those between the ages of 45 and 65.

Risk factors for Hashimoto’s include a family history of thyroid disorders, as well as specific environmental triggers. Several genetic polymorphisms (for example, changes to the HLA-DR gene) have been associated with autoimmune thyroiditis.[3. Jabrocka-Hybel, A., et al. “How far are we from understanding the genetic basis of Hashimoto’s thyroiditis?” International Reviews of Immunology Vol. 32, No. 3 (2013): 337–354] In addition, infectious diseases, excessively high iodine intake, selenium deficiency, and certain medications may also trigger this condition in those who have a genetic predisposition.

Hashimoto’s is a disease process characterized by progressive destruction of the thyroid gland resulting in hypothyroidism. It can be diagnosed by any of the following: 1) enlargement of the thyroid gland / goiter, 2) high levels of antibodies against thyroid peroxidase or thyroglobulin, 3) fine-needle aspiration of the thyroid showing immune-cell infiltration of the gland, 4) an ultrasound showing an enlarged thyroid, or 5) radioactive iodine uptake scan showing a specific pattern of diffuse iodine uptake.

People with Hashimoto’s often experience different symptoms, of varying severity. Some patients may experience no symptoms at all, whereas those experienced by others may be quite severe. As the condition results in progressive destruction, symptoms of hypothyroidism gradually appear.

Hypothyroidism symptoms include:

Weight gain
Dry skin
Hair loss
Sensitivity to cold

These symptoms often worsen over time, as the gland is progressively destroyed. Another aspect of Hashimoto’s is that patients may experience temporary symptoms of hyperthyroidism — this is known as “Hashitoxicosis”.[4. Nabhan, Z.M., N.C. Kreher, and E.A. Eugster. “Hashitoxicosis in children: clinical features and natural history”. The Journal of Pediatrics Vol. 146, No. 4 (2005): 533–536]

Symptoms of Hashitoxicosis include:

Weight loss
Palpitations & rapid heart rate
Thinning skin

Hashitoxicosis occurs as a result of disturbance of the thyroid follicles, which causes the release of excessive thyroid hormone. However, as the disease progresses, the predominant symptomatology becomes more one of hypothyroidism.

This article will discuss the underlying causes of autoimmune thyroiditis, the relationship of the intestinal microbiology and gut barrier in provoking and aggravating the disease. Celiac disease and the role of gluten in Hashimoto’s, and nutritional relationships between iodine and selenium in this disease will also be discussed.

Hashimoto’s & The Gut

In recent years, the intestinal immune system and bacterial flora have been found to play a key role in many different autoimmune diseases, such as rheumatoid arthritis.[5. Ebringer, A. and T. Rashid. “Rheumatoid arthritis is caused by a Proteus urinary tract infection”. APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica 2013 Aug 29. [Epub ahead of print] The intestine is in continuous contact with a wide variety of antigens from both food and microorganisms. Beneficial microorganisms in the intestine provide great benefit by forming protective barriers, aiding in the digestion and assimilation of nutrients, and in the development of the intestinal immune system. Fermentation products of intestinal bacteria also may inhibit inflammatory chemicals such as TNF-alpha, IL-6, and NF-kB[6. Segain, J.-P., et al. “Butyrate inhibits inflammatory responses through NFkB inhibition: implications for Crohn’s disease”. Gut Vol. 47, No. 3 (2000): 397–403],[7. Macdonald, T.T. and G. Monteleone. “Immunity, inflammation, and allergy in the gut”. Science Vol. 307, No. 5717 (2005): 1920–1925] that can be part of autoimmune destruction. Overall, a well-balanced gut flora is important when considering autoimmune diseases such as Hashimoto’s.

In addition to the microbes that live in the intestine, the intestinal lining itself is coming more to the forefront of research in autoimmune disease. The intestinal lining provides a barrier that prevents both pathogenic and nonpathogenic bacteria from entering into highly immunoreactive areas of the body, such as the bloodstream. If this mucosal barrier is disrupted, the immune cells of the intestine can become exposed to bacterial and dietary compounds that would normally be kept out. This in turn can lead to activation of the immune system and the development of autoimmune diseases.[8. Vaarala, O., M.A. Atkinson, and J. Neu. “The ‘perfect storm’ for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity”. Diabetes Vol. 57, No. 10 (2008): 2555–2562] When this happens, intestinal cells change, and the overall permeability of the intestine increases. This has been demonstrated in conditions such as autoimmune type 1 diabetes, and similar changes in intestinal structure have also been detected in patients with Hashimoto’s disease.[9. Cindoruk, M., et al. “Increased colonic intraepithelial lymphocytes in patients with Hashimoto’s thyroiditis”. Journal of Clinical Gastroenterology Vol. 34, No. 3 (2000): 237–239],[10. Sasso, F.C., et al. “Ultrastructural changes in enterocytes in subjects with Hashimoto’s thyroiditis”. Gut Vol. 53, No. 12 (2004): 1878–1880]

A concept known as “molecular mimicry” has also been implicated in Hashimoto’s and other autoimmune diseases. For example, Yersinia enterocolitica is an intestinal pathogen that can be transmitted to humans through pets and domestic animals, including pigs, with infections acquired via ingestion of contaminated food or water. There have been several studies correlating Yersinia infection with thyroid autoimmunity, including a trial reported in Clinical Microbiology and Infection, which claimed that the prevalence of antibodies to Yersinia was 14 times higher in people with Hashimoto’s than in those within a control group.[11. Chatzipanagiotou, S., et al. “Prevalence of Yersinia plasmid-encoded outer protein (Yop) class-specific antibodies in patients with Hashimoto’s thyroiditis”. Clinical Microbiology and Infection Vol. 7, No. 3 (2001): 138–143] The researchers concluded that there may be a strong causative relationship between this pathogen and autoimmune thyroiditis.

One important point to consider is that although probiotic flora may be beneficial, the choice of strains is crucial. Some probiotic strains have anti-inflammatory effects and provide benefit in autoimmune disease, whereas other strains may aggravate autoimmunity. For instance, a study conducted in Denmark found that specific strains of Lactobacillus acidophilus and Bifidobacterium bifidum reduced regulatory T-cell activity, which could increase inflammation and aggravate Hashimoto’s,[12. Schmidt, E.G.W., et al. “Antigen-presenting cells exposed to Lactobacillus acidophilus NCFM, Bifidobacterium bifidum BI-98, and BI-504 reduce regulatory T cell activity”. Inflammatory Bowel Diseases Vol. 16, No. 3 (2010): 390–400] whereas another study found that Lactobacillus rhamnosus HN001 and Bifidobacterium lactis HN019 reduced inflammation without affecting Hashimoto’s antibodies.[13. Zhou, J.S. and H.S. Gill. “Immunostimulatory probiotic Lactobacillus rhamnosus HN001 and Bifidobacterium lactis HN019 do not induce pathological inflammation in mouse model of experimental autoimmune thyroiditis”. International Journal of Food Microbiology Vol. 103, No. 1 (2005): 97–104]

Celiac Disease, Gluten & Hashimoto’s

There have been several studies correlating celiac disease and Hashimoto’s thyroiditis. As these are both autoimmune conditions, the topic has been the subject of much research, which has found a clear link between the two.

In a Dutch study on 104 people with Hashimoto’s,[14. Hadithi, M., et al. “Coeliac disease in Dutch patients with Hashimoto’s thyroiditis and vice versa”. World Journal of Gastroenterology Vol. 13, No. 11 (2007): 1715–1722] it was found that there was a significantly increased chance of having markers of celiac disease, including antibodies to gliadin and/or damage to the small intestine. Nearly 50% of the Hashimoto’s patients had the genes for celiac disease (HLA-DQ2). In a separate test within the same study, 184 patients with celiac disease were tested for Hashimoto’s antibodies, and it was found that 21% of them were positive. In some patients with celiac disease, avoidance of gluten may actually eliminate thyroid specific antibodies.[15. Chen, X., et al. “Effect of excessive iodine on immune function of lymphocytes and intervention with selenium”. Journal of Huazhong University of Science and Technology. Medical Sciences Vol. 27, No. 4 (2007): 422–425] 

Gluten & Zonulin

Zonulin is a fascinating intestinal protein that was recently discovered by Dr. Allessio Fasano. Its main function is to regulate the passage of materials from the intestine to the bloodstream. Tight junctions are the areas in which adjacent intestinal cells come into contact with each other, forming an impermeable barrier. They are crucial in that they prevent foreign particles, microbes, and improperly digested food from entering the body. When too much zonulin is released, the tight junctions can become leaky, and as described in the previous section, allow immunologically reactive molecules such as food antigens and microbes to enter into the bloodstream,[16. Fasano, A. “Zonulin, regulation of tight junctions, and autoimmune diseases”. Annals of the New York Academy of Sciences Vol. 1258 (2012): 25–33] causing inflammatory activation.

Interestingly, even in people who do not have celiac disease, consuming gliadin (a component of gluten) increases the release of zonulin and temporarily causes “leakiness” in the intestinal barrier, also known as “leaky gut”.[17. Drago, S., et al. “Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines”. Scandinavian Journal of Gastroenterology Vol. 41, No. 4 (2006): 408–19] In people who carry the HLA-DQ gene (approximately 30% of the population, and around 50% of Hashimoto’s patients) an excessive amount of zonulin is released when gliadin is consumed. For these patients, gut permeability is even more intensive. Once particles can enter the bloodstream through this leaky barrier, we are again faced with antigens entering the bloodstream, leading to aggravation or triggering of autoimmunity.[18. Fasano, A. “Leaky gut and autoimmune disease”. Clinical Reviews in Allergy & Immunology Vol. 42, No. 1 (2012): 71–78]

Selenium & Iodine

Iodine is a key nutrient for thyroid function. It combines with thyroglobulin to make the key thyroid hormones T3 and T4, so as you can imagine, its balance is crucial for the function of the gland.

It is well known that the intake of excessive iodine is linked to triggering Hashimoto’s thyroiditis.[19. Mazokopakis, E.E., et al. “Effects of 12 months treatment with l-selenomethionine on serum anti-TPO levels in patients with Hashimoto’s thyroiditis”. Thyroid Vol. 17, No. 7 (2007): 609–612] The literature is full of cases of iodine-induced autoimmune thyroid disease, with many studies correlating the increased incidence of Hashimoto’s in countries where iodine intake is higher. The high doses of iodine in patients with a predisposition to Hashimoto’s seem to trigger the production of T lymphocytes,[20. Xu, J., et al. “Supplemental selenium alleviates the toxic effects of excessive iodine on thyroid”. Biological Trace Element Research Vol. 141, No. 1–3 (2011): 110–118] and these immune cells then turn on the thyroid gland itself, resulting in decreased overall thyroid function over time.

That said, many practitioners do use iodine therapy with Hashimoto’s patients. This part of the article will discuss the critical balance between two key thyroid nutrients, iodine and selenium. I also have another article with information on the use of iodine in patients who are trying to conceive or are suffering with infertility and Hashimoto’s.

Much of the research about using iodine for patients with Hashimoto’s involves the effect of optimal selenium status. Selenium is a mineral that is found in high concentration in the thyroid, and the selenoproteins in that gland are involved in antioxidant defense; specifically in the action of glutathione peroxidase[21. Xue, H., et al. “Selenium upregulates CD4+CD25+ regulatory T cells in iodine-induced autoimmune thyroiditis model of NOD.H-2h4 mice”. Endocrine Journal Vol. 57, No. 7 (2010): 595–601] — a major cellular protector. These antioxidant defense mechanisms protect the thyroid from the reactive oxygen species that are produced as a byproduct of thyroid hormone synthesis. The three key enzymes involved in the activation and inactivation of thyroid hormones are also selenium-based in structure.

There are numerous studies finding that selenium supplementation reduces thyroid autoimmune antibodies. A study of 80 women with Hashimoto’s disease found that supplementation of 200 mcg of selenomethionine reduced anti-TPO antibodies by 21%,[22. Contempre, B., et al. “Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium”. The Journal of Clinical Endocrinology and Metabolism Vol. 73, No. 1 (1991): 213–215] and many other studies support this finding. Supplementation of selenium is without doubt of great benefit for patients with Hashimoto’s, but what about the balance between iodine and selenium?

An animal study completed in China set out to test the hypothesis that the toxicity induced by excessive iodine intake might actually be induced by selenium deficiency.[23. Chong, W., et al. “Multifactor analysis of relationship between the biological exposure to iodine and hypothyroidism” (article in Chinese). Zhonghua Yi Xue Za Zhi Vol. 84, No. 14 (2004): 1171–1174] The study found that when iodine was given in high doses, it decreased the activity of thyroid enzyme thyroid peroxidase, changed the cell structure to a goiter-like appearance, and reduced the protective glutathione in the thyroid gland. However, when selenium was supplemented along with the iodine, these all returned back to control levels.

Another study found something quite similar: three groups of mice were included, including a healthy control group and two groups with iodine-induced Hashimoto’s. One of the thyroiditis groups was given selenium and one was not, but both were given high amounts of iodine. The selenium group had completely reversed the thyroiditis pattern on biopsy after eight weeks of supplementation, despite continuing on the high dose of iodine.[24. Tong, Y.J., et al. “An epidemiological study on the relationship between selenium and thyroid function in areas with different iodine intake” (article in Chinese). Zhonghua Yi Xue Za Zhi Vol. 83, No. 23 (2003): 2036–2039] In the non-selenium group, the destructive pattern in the thyroid gland remained.

Each of these studies indicates that achieving good selenium status can reverse the stimulation of thyroiditis caused by excessive amounts of iodine. The amount in these studies corresponds to approximately 200–400 mcg per day of selenium. It is important to note that selenium can be toxic, and that supplementing selenium in conditions of iodine deficiency may be harmful for thyroid function.

Another interesting point is that the areas of the world where Hashimoto’s increased after iodization of salt were areas in which selenium deficiency is predominant as well. For example, a study comparing different provinces in China indicated that the provinces with the lowest intakes of iodine also had the lowest incidences of Hashimoto’s. Coincidentally, these provinces were also more deficient in selenium. Thus, we can conclude that selenium status may play a key role in preventing autoimmune thyroiditis, and that the balance between iodine and selenium is important for thyroid function. It is often helpful to check iodine status before supplementing higher doses of iodine. Urinary iodine testing is the most accurate (either a 24-hour urine iodine, or dried urine iodine test).

If you have been diagnosed with or suspect a thyroid problem, we recommend consultation with a licensed naturopathic doctor prior to undertaking high dose iodine or selenium supplementation.

About Fiona McCulloch ND

Dr. Fiona McCulloch is a board certified Naturopathic Doctor who has been in practice since 2001 in Toronto, Canada. Dr. Fiona is the founder and owner of White Lotus Integrative Medicine, a busy urban clinic specializing in women’s health, endocrinology, and fertility. Her clinical focus is on the treatment of fertility and hormonal conditions and she is an avid writer and researcher, developing naturopathic treatment protocols for hormonal concerns based on the most current evidence.

Dr. McCulloch has published a variety of articles in naturopathic journals and is currently working on her first book on the naturopathic treatment of PCOS by clinical phenotype. She lives in Toronto with her husband and 3 boys. She can be found on her Dr Fiona McCulloch ND Facebook Page and on Twitter @DrFionaND.


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About Dana Trentini

Who knew that little butterfly-shaped thyroid gland at the base of my neck could affect my life so completely? I founded Hypothyroid Mom in memory of the unborn baby I lost to hypothyroidism. Winner of two 2014 WEGO Health Activist Awards: Health Activist Hero & Best In Show Twitter. *Hypothyroid Mom includes Affiliate links. Connect with me on Google+

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