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Several treatments claim to be first-line treatments. These treatments include radioactive iodine, antithyroid medications, and beta blockers. Depending on the severity and progression of the disease, as well as provider recommendation, treatment could involve one or more aspects.

Treatment with radioactive iodine slowly kills the thyroid cells and works by decreasing the production of hormones and shrinking the gland over time. Surgery to remove the thyroid might be recommended in severe cases.  In less severe or early onset cases, anti-thyroid medications such as methimazole might be prescribed to slow the progression and help manage the effects of the disease.  corticosteroids can also help certain ailments of the disease such as pressure behind the eyes. Beta-blockers are not used to manage the thyroid, rather they protect the heart while thyroid-stabilizing medications take effect.

Cleveland Clinic, 2022. Graves disease.  Diseases and conditions.  http://my.clevelandclinic.org

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Graves disease (GD) is an autoimmune disorder caused by an overproduction of thyroid hormones. Normally the thyroid function is regulated by a hormone released by the pituitary gland. When needed, the body's immune system produces antibodies designed to target specific virus, bacterium and other antigens. However in Graves' Disease, thyrotropin receptor antibody, mimics the regulatory pituitary hormone. By mimicking the action of TSH, it binds and activates the receptor causing an overproduction of thyroid hormones and hypertrophy of thyroid follicular cells.

Although it is not known exactly how a malfunction in the body's disease fighting immune system causes GD, we do know it is a multifactorial disease that is caused by both genetic and environmental factors that lead to the loss of immune tolerance to thyroid antigens. Its hallmarks include elevated levels of serum thyroxine (T4) and triiodothyronine (T3) and is characterized by unique associations of ophthalmopathy, dermopathy, goiter, and thyrotoxicosis.

Menconi, F. Marcocci, C. & Marino, M. (2014). Diagnosis and Classification of Graves' Disease. Autoimmune Reviews, vol 13(4-5), pp. 398-402. https://doi.org/10.1016/j.autrev.2014.01.013.

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Some observable symptoms that are used in diagnosing Grave's disease are:

-weight loss
-shaky hands
-rapid or irregular heart beat
-trouble sleeping
-increased appetite
-irritability or nervousness

It is important to note that these symptoms will vary between individuals and these are interconnected with symptoms of hyperthyroidism.

U.S. Department of Health and Human Services. (n.d.). Graves’ disease - niddk. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/endocrine-diseases/graves-disease#symptoms

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Conformity of disease to definition of hypersensitivity:

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Conformity of disease to definition of hypersensitivity:

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Type ll hypersensitivity is defined as being tissue-specific which technically categorizes Graves disease. However, it is more appropriately classified under type 2 in the subtype V, as type V represents the action of antibodies being made against a specific hormone receptor.  This action occurs in Graves disease and is apparent within the thyroid causing hyperthyroidism.  Graves disease is caused by antibodies called thyroid-stimulating immunoglobulin (TSI) that target and bind to the thyroid cells mimicking the action of thyroid-stimulating hormone.  This action stimulates the thyroid to overproduce hormones.

Rogers, J. (2022) . McCance & Huether's Pathophysiology (9th ed.). Elsevier Health Sciences (US). pg (694). https://pageburstls.elsevier.com/books

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-Female
-30 years old or older
-Postpartum women
-Smokers
-Constantly under a lot of stress
-Exposed to environments that have high levels of iodine

All these traits increase the likelihood of getting Graves' Disease. It's also important to note that individuals who have certain autoimmune diseases are susceptible to having Grave's disease. Individuals who have the following are at an increased risk; type 1 diabetes, autoimmune gastritis, rheumatoid arthritis, and those who have a family history of Grave's disease.

Yale Medicine. (2023, May 16). Graves’ disease. Yale Medicine. https://www.yalemedicine.org/conditions/graves-disease

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Cellular, tissue, organ level pathophysiology:

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Cellular, tissue, organ level pathophysiology:

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In Graves' Disease, there are 4 thyroid antigens: thyroglobulin, thyroid peroxidase, sodium-iodide symporter and thyrotropin receptor that direct B and T lymphocyte mediated autoimmunity. However, the primary auto antigen is the thyrotropin receptor. The thyrotropin receptor antibody overrides the body's normal regulation of the thyroid. B lymphocytes primarily synthesize the antibodies TSI, thyroid stimulating immunoglobulins, within thyroid cells but it can also be synthesized in lymph nodes and bone marrow. B cells are stimulated by T lymphocytes which get sensitized by antigens in the thyroid gland. Normally thyroid receptors act as docking station for TSH, but TSI tricks the body causing the thyroid to grow and make more thyroid hormones (especially triiodothyronine T3 and thyroxine T4) leading to hyperthyroidism and thyromegaly.

Although there is no known etiology for Graves' Disease, there are a few susceptibility genes associated with it including the immune regulatory genes: HLA-DR, PTPN22, CTLA4, CD40, FCRL3 and SCGB3A2. HLA-DR plays an important role in helping to recognize CD4+ T helper cells while protein tyrosine phosphatase non receptor type 22, PTPN22, has been associated with HLA and plays a role in T cell regulation. CTLA2 is expressed on regulatory T cells and functions as an immune checkpoint and downregulates immune responses. FCRL3 is an Fc receptor like protein 3 that plays a role in regulating the immune system and contains immunoreceptor tyrosine activation and inhibitory motifs. SCGB3A2 is a homodimeric protein that plays a role in inflammation and tumorigenesis. Mutations in these genes greatly increase risk of autoimmune diseases including GD.

Graves' disease affects many organs including heart, skeletal muscle, eyes, skin, bone and liver. If left untreated, it can change the function and structure of the heart muscles causing heart rhythm disorders and heart failure. Some other issues include ophthalmopathy. This is caused by inflammation, cellular proliferation, increased growth of extraocular muscles and increased retro-orbital connective and adipose tissues due to TSI and cytokines released by killer cells. Cytokines and thyroid stimulating antibodies synthesize GAG which causes muscle swelling by trapping water. Orbital connective tissue accumulation, inflammation and edema results in protrusion of eyeball, periorbital edema, extraocular muscle weakness leading to double vision. Another manifestation includes dermopathy that is characterized by subcutaneous swelling of legs and erythematous skin. It is associated excessive amounts of hyaluronic acid production in dermis and subcutaneous tissue. It can give appearance of clubbing of the fingers.

Pokhrel, B. & Bhusal, K. Graves Disease. (2023) National Library of Medicine. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK448195/
S. Khan, M., S. Lone, S., Faiz, S., Farooq, I., & Majid, S. (2021). Graves’ Disease: Pathophysiology, Genetics and Management. IntechOpen. doi: 10.5772/intechopen.98238