Sean Ma

A11693261
12/12/2014
Genetic Disorder Essay- Graves Disease
Upon receiving this assignment, I immediately knew that I wanted to research a genetic
order that had directly affected someone in my life. However, I also wanted to research a
disorder that wasnt common knowledge, or that I had much prior knowledge of beforehand. So
while my grandfather suffers from type 2 diabetes, I felt like I already knew too much about the
disorder. My mother had once mentioned a problem with her thyroid, but never elaborated on it,
and because it didnt appear to be too serious I did not press the issue. Upon further investigation
I discovered that Graves disease is a common hyperthyroid disease in women, and its symptoms
matched much of what my mother had been experiencing over the past couple years. This
assignment provided the perfect opportunity to become more knowledgeable about the disease.
The thyroid is a gland in the lower neck that produces hormones which regulate
important body functions such as growth and development, heart rate, temperature, and
menstrual cycles (1). Hyperthyroidism can result when too much thyroid hormone is produced,
while hypothyroidism occurs when too little is produced. Graves disease is an autoimmune
hyperthyroid disease that is a result of an overactive thyroid which produces more hormones than
the body requires. This can result in symptoms that include fatigue, weight loss, a rapid and
irregular heartbeat, increased anxiety, frequent bowel movements, and difficulty sleeping.
Women with Graves disease often have irregular menstrual cycles as well. Some individuals
afflicted with Graves experience a swelling of the thyroid, called a goiter, which can cause
problems with breathing and swallowing (1). About 25 percent of people with Graves disease
also develop Graves opthalmopathy (GO), which is a result of the autoimmune system attacking
tissues around the eyes. This causes inflammation behind the eye socket, producing bulged-out

eyes that are often experience irritation, increased light sensitivity, or in extreme cases, even loss
of vision (2). Graves disease affects around 1 in 200 people, and is more common in women
than in men, likely because of hormonal factors (1).
While it is not entirely clear how Graves disease is inherited, studies have shown that
having a relative with the disease increases a persons chance of developing Graves (2). The
disease is likely a result of many genetic and environmental factors. As a result, a single
chromosome has not been identified as the direct cause for Graves disease. However, loci for
susceptibility to the condition have been mapped to chromosomes 14q31 and 20q13 (3). Studies
in the 1940s and 1960s provided conflicting ideas about the dominant versus recessive nature of
the disease, but there was not conclusive evidence of either.
Tests for Graves disease simply involve tests for thyroid function. Typically the first test
performed is to measure the level of thyroid-stimulating hormone (TSH) in a blood sample. A
low TSH level indicates that the thyroid is overactive and is producing large amounts of thyroid
hormone, indicating hyperthyroidism and therefore a strong possibility of Graves disease (4).
Additional tests for Graves measure levels of thyroxine (T4), the major hormone excreted by the
thyroid, and triiodothyronine (T3), a converted state of T4. Hyperthyroidism results in higher
levels of T4 and T3, and conversely, hypothyroidism results in lower levels. Thyroid activity can
also be detected by tracing a small amount of radioactive iodine as it is ingested. T4 contains
iodine, so iodine is taken from the blood stream to create additional T4. If the thyroid takes up a
large amount iodine, this can be indicative of hyperthyroidism and Graves disease (4).
Graves disease is typically treated in three different ways. Radioiodine therapy involves
ingesting radioactive iodine-131. Iodine-131 is stronger than the iodine used in tests, and
gradually destroys part or all of the cells of the thyroid gland, therefore stopping the production

of the thyroid hormone. However, this almost always results in hypothyroidism because no
thyroid hormone is produced, so patients must take medication that provides a synthetic hormone
(2). While use of radioiodine therapy is not known to cause birth defects, it is not recommended
for pregnant women. Instead, they are usually treated with antithyroid medication, which inhibits
production of the thyroid hormone. However use of antithyroid medication typically does not
have permanent results, so medication is generally given to patients before they undergo
radioiodine therapy or thyroid surgery(2). Thyroid surgery involves the direct removal of the
entire thyroid gland, called a thyroidectomy, and is the least used of the three treatment methods.
Once again, patients that have had their thyroid removed require thyroid hormone medication to
replace the lack of hormone production. While radioiodine therapy has been by far the most
common treatment method, a study in 2010 on sixty five thyroidectomy patients revealed that
surgery is the most rapid and cost effective cure for Graves disease. All sixty five of the
thyroidectomy patients were cured of Graves, and none experienced a recurrence of the disease
afterwards (5). While some complications arose during the surgeries, there were no major or
lasting negative effects. In the future, perhaps the frequency of thyroidectomies as a treatment for
Graves disease will rise as additional developments and more experienced surgeons further
increase the effectiveness and safety of the procedure.
Other potential treatments of Graves disease are also on the rise. Selenium, a powerful
antioxidant, has been used to successfully slow the progression of mild Graves opthalmopathy
and ease some of the discomfort caused by the disease. This comes from seleniums presence in
selenoproteins, which catalyze the breakdown of hydrogen peroxide and lipid hydroperoxide,
two products of hyperthyroidism. Selenium has also been shown to slow the formation of
proinflammatory cytokines, reducing the inflammatory effects of GO (6). While further research

is needed, selenium is a promising alternative for therapy of patients with severe Graves disease
and opthalmopathy. Rituximab (RTX), a human antibody, has also been proposed as a potential
treatment for Graves disease. RTX interrupts aspects of the immune response that underlie
Graves by destroying immune system B cells. As a result, RTX has been used in the treatment of
a variety of autoimmune diseases. Application of RTX seems to be effective on patients who are
unresponsive to typical antithyroid drugs, and may also prolong remission for longer periods of
time than these conventional drugs (7). However, RTX therapy is quite expensive, and additional
studies are needed before it can become a more widely used treatment for Graves disease.

Sources:

(1) Genetics Home Reference. (2014, December 9). Graves disease. Retrieved December 11,
2014, from http://ghr.nlm.nih.gov/condition/graves-disease
(2) National Endocrine and Metabolic Diseases Information Service (NEMDIS). (August 10,
2012.). Graves Disease. Retrieved December 11, 2014, from
http://www.endocrine.niddk.nih.gov/pubs/graves/#ophthalmopathy
(3) Online Mendelian Inheritance in Man, OMIM. Johns Hopkins University, Baltimore, MD.
MIM Number: {275000}: {September 9, 2014}: . World Wide Web URL:
http://www.omim.org/entry/275000
(4) American Thyroid Association. (2012, June 4). Thyroid Function Tests. Retrieved December
11, 2014, from http://www.thyroid.org/blood-test-for-thyroid/
(5) Feliciano, D. V., & Lyons, J. D. (2011). Thyroidectomy is optimal treatment for Graves'
disease. Journal of the American College of Surgeons, 212(4), 714-720.
(6) Duntas, L. H. (2012). The evolving role of selenium in the treatment of Graves' disease and
ophthalmopathy. Journal of thyroid research, 2012.
(7) Hegeds, L., Smith, T. J., Douglas, R. S., & Nielsen, C. H. (2011). Targeted biological
therapies for Graves disease and thyroidassociated ophthalmopathy. Focus on Bcell depletion
with Rituximab. Clinical endocrinology, 74(1), 1-8.