Katlyn Mayer’s Advanced Biochemistry Blog

Background Information and History of the Disease

Background Information

Hashimoto’EPS Thyroiditis is an autoimmune disease that causes hypothyroidism. The classic signs, symptoms, and clinical findings of the disease include those of any generic hypothyroidism: fatigue, weight gain, fluid retention in the face and neck, feeling cold, irregular heart rates and rhythms, and heavy menstrual flow in women. Like so many other autoimmune diseases where antibodies attack healthy tissues, antithyroid antibodies attack the tissue of the thyroid and can create nodules. Antibodies against thyroid peroxidase and/or thyroglobulin cause gradual degradation of the follicles in the thyroid creating nodules.  In severe cases, thyroid lumps can be visualized through the neck. Interestingly enlargement of the thyroid is due to lymphocytic infiltration and fibrosis rather than actual thyroid tissue growth. As it turns out, one of the clinical tests for the disease is to look for these anti-thyroid antibodies in the blood.

Nodules that develop on the thyroid can be visible through the neck if they get large enough.

Hashimoto’s Thyroiditis has an interesting history. It was named after the Japanese physician who discovered it, Hakaru Hashimoto. He first published on the disease and its characteristic lymphocytic infiltration of the thyroid in 1912. By 1957, the disease was named an autoimmune disorder and was the first autoimmune disorder classified as having an organ-specific target– the thyroid.

 

Dr. Hakaru Hashimoto circa 1912.

Many of the studies referenced throughout these theme pages examine patients with Grave’s Disease as a means to comparison to Hashimoto’s Thyroiditis. It is important to understand the differences between these two autoimmune thyroid conditions. As noted above, Hashimoto’s Thyroiditis is an autoimmune disease that results in hypothyroidism and its associated symptoms. Grave’s Disease, on the other hand, is an autoimmune thyroid condition which is known to cause hyperthyroidism and its associated symptoms. Often the two diseases are studied together in clinical trials as they are both autoimmune thyroid conditions with genetic and environmental factors contributing to its appearance in patients. While both diseases have antibodies against thyroid peroxidase, and it is not necessarily impossible for both diseases to appear in a patient at the same time, at the end of the day, Grave’s disease is an autoimmune disease causing hyperthyroidism (overproduction of thyroid hormone) while Hashimoto’s Thyroiditis, the disease focused on in these theme pages, is an autoimmune disease causing hypothyroidism (underproduction of thyroid hormone.)

One of the earlier findings in the disease was a phenomenon known as Hashitoxic Periodic Paralysis. This finding was present in both Graves Disease Patients and Hashimoto’s Thyroiditis patients as its main cause was speculated to be due to the antibodies against Thyroid Peroxidase. This paralysis event is characterized by tremors, weakness, and the sensation of paralysis. While Hashitoxic paralysis is not an incredibly common finding in those suffering from hypothyroidism and hyperthyroidism, it has been one of the signs and symptoms that has brought the Hashimoto’s Thyroiditis patient to the doctor. When a patient presents with these symptoms, it is up to the physician to determine what is causing the patient’s suffering and to rule out other diseases like Myesthenia Gravis.

As noted above, the disease has strong genetic and environmental causes.  Those who already suffer from other autoimmune diseases such as type 1 diabetes and celiac disease are more at risk for developing this form of hypothyroidism. Progressive downregulation of the gene can lead to low T3/T4 levels and compensatory low TSH levels. One of the genes that is associated with Hashimoto’s is Cytotoxic T-lymphocyte Antigen-4 (CTLA-4). The protein is an immune checkpoint which down regulates immune responses. While the gene is found on chromosome 2 and not a sex chromosome, the majority of those who suffer from Hashimoto’s disease are women. Those who suffer from the  disease demonstrate down-regulation of this gene. This down regulation event reduces the checkpoint activity and stops the inhibitory signal that is sent to T cells causing attack of the thyroid tissue in patients.

Some of the environmental factors that have been implicated in causing the disease include high iodine intake as well as selenium deficiency. These dietary factors can cause hypothyroidism—specifically Hashimoto’s Thyroiditis. Another environmental factor in Hashimoto’s Thyroiditis is vitamin D deficiency. While it is not entirely understood if the disease causes the deficiency or if the deficiency causes the disease, you can read more about this phenomenon on the page entitled “Biochemical Basis and Treatment of the Disease.” The vitamin D receptor is examined as a possible cause of this irregularity in the disease as well.

Bibliographic information found in Works Cited tab of this page.

2 comments

  1. Very well done articles. I started with the first intro page and had to dive deeper to learn. Is hypothyroidism hereditary? Also, are the treatments for hypothyroidism and Hashimoto’EPS Thyroiditis the same? It is interesting that women are more like to acquire the disease than men. Men are more likely to inherit X chromosome diseases because they only have one X chromosome. Is this disease on a certain chromosome? Women, on the other hand, have two X chromosomes so I would think that the other X chromosome would turn off this “bad” gene. I would be interested to learn even more about the connection between VDR and Hashimoto’s. Overall, very professional and I learned a lot of new information!

    1. Hashimoto’s disease is hereditary, but researchers are not entirely sure of the mechanism. Hashimoto’s is one class of hypothyroidism, but most if not all hypothyroidism diseases are treated with levothyroxine. It is the safest and most effective treatment on the market today. I was also incredibly surprised that women inherit the disease over men. I immediately thought of diseases linked to sex chromosomes which are inherited much more often by men as they only have one X chromosome. As it turns out, the mutation in CTLA-4 is on chromosome 2– an autosomal chromosome which both men and women have two copies of. In our advanced biochemistry class this semester, we learned about the importance of vitamin D in the immune system, and it will be interesting to follow the literature over the years to see how it can be beneficial in treating autoimmune disorders!

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