Physiological Review Of Graves Disease Biology Essay

Published: Last Edited:

This essay has been submitted by a student. This is not an example of the work written by our professional essay writers.

Graves Disease is the most common type of hyperthyroidism and involves multiple physiological processes within the body. GD results from the presence of autoantibodies that mimic thyroid-stimulating hormone and cause an overproduction and release of thyroid hormones into the bloodstream (Nystrom, 2011). Factors contributing to the production of the autoantibodies include genetic susceptibility (Bahn, Davies, Latif & Yin, 2012), in addition to environmental factors, including stress (Effraimidis, Tijssen, Brosschot, & Wiersinga, 2012), smoking, and certain viruses and medications (Dalan & Leow, 2012). Consequently, symptoms of anxiety occur (Weeks, 2005), in addition to an enlarged thyroid (Nystrom, 2011), ocular symptoms (Bahn & Khoo, 2007), a rash known as pretibial myxedema (Houck, Kauffman, Missner & Ramsay, 1998), and abnormal swelling of the hands (Nystrom, 2011). Gaining an understanding of the physiological mechanisms of action involved in the development and treatment of GD is important for healthcare professionals who treat patients who may have this condition.

Physiological Review of Grave's Disease

Grave's Disease (GD) is an autoimmune disease that was first discovered by Robert Graves in 1835 (Weeks, 2005). GD is the most prevalent a type of hyperthyroidism (Weeks, 2005), a condition where the thyroid gland synthesizes and releases hormones in excess of that required by the body (Nystrom, 2011). Thyroid hormones are important for maintaining the body's metabolism and have mechanisms that interact with the immune system (Effraimidis, Tijssen, Brosschot, &Wiersinga, 2012). When reviewing the mechanisms of action of GD, it is important to include the physiological origin of the disease, as well as symptomology, epidemiology, diagnosis, and treatment options.

The Thyroid Gland

To gain a clear understanding of the mechanisms of action of GD, it is important to first have a basic understanding of the normal processes of the thyroid gland. The thyroid gland is an endocrine gland that is found in the lower neck below the larynx and wraps around the trachea (Mokhasi et al., 2012). This gland produces hormones called thyroxin (T4) and triiodothyronine (T3) (Weeks, 2005). T3 and T4 are produced to maintain the body's metabolism but T3 works at a faster pace (Weeks, 2005). Hormone production and release are controlled by an area of the brain known as the hypothalamus, which produces thyrotropin-releasing hormone (TRH; Weeks, 2005). TRH then stimulates the pituitary to release thyroid-stimulating hormone (TSH), which stimulates the thyroid to release T3 and T4 (Weeks, 2005). If the amount of T3 and T4 in the bloodstream is low, the pituitary releases TSH to increase the release of these hormones from the thyroid gland (Weeks, 2005). If the level of these hormones in the bloodstream is high, the pituitary inhibits TSH from being released, creating a negative feedback (Weeks, 2005). Although the presence of TSH is essential for the release of thyroid hormones (Weeks, 2005), the synthesis of T3 and T4 depends on the presence of iodine within the cells (Laurberg, 2012).

Iodine, a common compound found in foods with salt, is also essential for normal thyroid processes to occur (Laurberg, 2012). Adults are recommended to consume 150 micrograms of iodine each day (Nystrom, 2011). Once iodine is consumed and released from the small intestine into the bloodstream, 30 percent of the compound travels to the thyroid gland where it creates an electrochemical gradient around the basal membrane of the follicle cells located in the thyroid (Nystrom, 2011). The remaining 70 percent of the consumed iodine is excreted in urine (Nystrom, 2011). The pump allows iodide to pass through the membrane, which stimulates the iodine channels to open (Laurberg, 2012). This permits iodine to enter the cell and contribute to thyroid hormone synthesis (Laurberg, 2012). A disruption of these processes may result in numerous thyroid deficiencies, including GD (Weeks, 2005).

Grave's Disease

There are specific physiological mechanisms that result in the symptoms associated with GD (Weeks, 2005). For an unknown reason, individuals with this disease produce T-lymphocytes that are sensitive to antigens located in the thyroid gland (Weeks, 2005). The T-lymphocytes then stimulate B-lymphocytes to release a specific type of autoantibody, called thyrotropin receptor antibody (TRAb), which bind to the TSH receptor site on follicular cells in the thyroid (Mathews & Syed, 2011). As a result, TRAb blocks TSH from binding to the receptor (Mathews & Syed, 2011). Because TRAb have the same effects on the thyroid gland as TSH, an overproduction of thyroid hormones occur and the negative feedback loop is inhibited (Mathews & Syed, 2011). Specifically, after TRAb binds to the receptor site there is an increase in production of a second messenger called cyclic adenosine monophosphate, which facilitates the transfer of hormones into cells (Richards, 2001). Additionally, the presence of TRAb results in increased iodine uptake and increased production of T3 and T4 (Dalan & Leow, 2012). An overabundance of these hormones result in a 60 to 100 percent increase of the body's metabolism (Weeks, 2005). Additionally, as individuals with GD get older, the thyroid gland produces nodules that release T3 and T4 spontaneously, without responding to stimulation or inhibition from the pituitary (Week, 2005). Several factors have been demonstrated to influence the onset of these physiological reactions (Bahn, Davies, Latif & Yin, 2012).


A complex combination of genetic and environmental factors has been demonstrated to increase the chances one has of developing GD (Bahn, Davies, Latif & Yin, 2012). Two distinct groups of genes have been found to be related to the disease, including genes involved in many autoimmune diseases, as well as genes that regulate the thyroid gland (Bahn, Davies, Latif & Yin, 2012). Studies have shown that it is common for several family members across generations to develop the disease (Weeks, 2005).

Environmental factors influencing the development of GD include viruses, smoking, and medications (Dalan & Leow, 2012). These exogenous factors contribute to GD by either modifying the TSH receptor site or changing the TSH structure in thyroid cells (Dalan & Leow, 2012). Additionally, abnormal levels of iodine exposure are also thought to influence the development of GD, due to the impact iodine has on thyroid hormone production (Nystrom, 2011). This interaction is dependent on the amount of iodine reserves already present within the individual (Nystrom, 2011).

Furthermore, environmental stress may play a role in the development of GD (Effraimidis, Tijssen, Brosschot, & Wiersinga, 2012). Stress activates the hypothalamic-pituitary-adrenal axis, which inhibits the response of a specific T cell, called Th1, and excites the response of another T cell, known as Th2 (Effraimidis, Tijssen, Brosschot, & Wiersinga, 2012). Th2 is typically predominant in the development of GD (Effraimidis, Tijssen, Brosschot, & Wiersinga, 2012). As a result of the physiological changes that occur involved in the progression of GD, several symptoms are present among patients with this disease (Weeks, 2005).


Due to the increase of metabolic regulating hormones in the bloodstream of an individual with GD, several symptoms are typically present (Weeks, 2005). In most cases of GD, individuals have a syndrome called thyrotoxicosis, which involves the activation of the sympathetic nervous system (Weeks, 2005). Individuals who have thyrotoxicosis typically have a heightened sensitivity to catecholamines, which are hormones important for the physiological responses associated with the fight or flight response (Nystrom, 2011). Thyrotoxicosis involves symptoms of anxiety, such as restlessness, irritability, weight loss, and fatigue (Nystrom, 2011). Additional symptoms are muscle weakness, brittle hair, and increased sweating (Brent, 2008). GD may also result in tremors, rapid heart rate, irregular menstruation, and increased bowel movements (Brent, 2008).

Many individuals with GD also experience ocular symptoms, including irritation of the eye, corneal abrasions, and tearing (Weeks, 2005). Additionally, the eyeballs become inflamed and appear enlarged, exposing region of the eye above the iris, and impairing the eyelids from completely closing (Weeks, 2005). Approximately 25 to 50% of individuals with GD have this symptom (Bahn & Khoo, 2007). Research has demonstrated that ophthalmopathy of GD stem from the reaction TSH autoantibodies have on the production of adipose tissue, or fat cells, in the cells of the eye (Bahn & Khoo, 2007). The antibodies increase the production of adipose tissue, resulting in increased fat and muscle volume within the orbital region, pushing the eyeballs forward (Bednarek, Wysocki, & Sowiñski, 2005; Bahn & Khoo, 2007). A recent study has demonstrated ophthalmopathy symptoms of GD to be the result of environmental or epigenetic factors, rather than genetic factors alone (Bahn, Davies, Latif & Yin, 2012).

Furthermore, GD may result in the development of dermatologic symptoms, abnormal swelling, and an enlarged thyroid gland (Weeks, 2005). Pretibial myxoedema, which is a red, painless rash on the skin, is a common symptom of GD (Nystrom, 2011). Although the exact mechanism of action resulting in this symptom is currently unknown, one hypothesis suggests TRAb stimulates a target cell in the skin to release an excess of glycosaminoglycans, which accumulate and create the rash (Houck, Kauffman, Missner & Ramsay, 1998), typically present in the front of the lower legs (Nystrom, 2011). An additional symptom called thyroid-associated acropachy is uncommon, but may present in individuals with GD as swelling of the hands and feet (Nystrom, 2011). In most cases of GD, an enlarged thyroid gland, or goiter, is also present, especially in young adults (Weeks, 2005). A goiter develops as the result of a chronic increase of iodine, which stimulates the release of TSH (Nystrom, 2011). Because a variety of symptoms may present with GD, a thorough medical evaluation is necessary for making an accurate diagnosis (Weeks, 2005).


Individuals are typically diagnosed with GD between the ages of 20 and 40 (Weeks, 2005). The condition occurs within one percent of the population (Bahn, Davies, Latif &Yin, 2012) and women are eight times more likely than men to develop GD (Gaffud, Lee, Solorzano, Prinz, & Weber, 2006). A diagnosis can be made after a thorough patient history is obtained, including an assessment of symptoms lasting for four to six weeks and the presence of opthalmopathy, a goiter, or pretibial myxoedema (Nystrom, 2011). A physical exam, along with diagnostic tests, should also be completed (Weeks, 2005). An early diagnosis of GD increases the chances of a better prognosis and several treatment options exist to increase a patient's chances of recovery (Weeks, 2005).


Unfortunately, there are no treatment modalities that target the underlying immunological pathology of GD (Nystrom, 2011). However, interventions have been developed to decrease the production of thyroid hormones (Nystrom, 2011). These treatment options include antithyroid medications, radioactive iodine, and surgery (Weeks, 2005). Factors that impact a physician's decision to recommend a specific course of treatment include age, presence of a goiter, pregnancy, and history of recurrence (Nystrom, 2011).

Although antithyroid medications typically have positive short-term effects, the risk of recurrence has been found to be between 40 and 60 percent (Brent, 2008). Currently, two antithryoid drug treatment models exist for treating GD (Nystrom, 2011). One model involves the administration of the medication at the lowest dose that will achieve a normal level of T3 and T4 in the bloodstream (Brent, 2008). These results typically occur within three to four weeks of starting the medication (Brent, 2008). The second model is referred to as block and replace therapy and is implemented when a full dose of an antithyroid drug is administered to completely inhibit production of thyroid hormone (Nystrom, 2011). After 2 to 4 weeks, patients begin taking T4 daily with a gradual dosage increase (Nystrom, 2011). A patient who does not respond well to an antithyroid intervention may be recommended to undergo radioiodine therapy or surgery (Nystrom, 2011).

Radioiodine treatment may also be used to target GD (Carceller et al., 2011). This strategy targets GD as radioactive iodine is transported into the cell via the iodine pump and destroys surrounding thyroid tissue (Hayes & O'Connell, 2012). This method typically results in a gradual improvement of symptoms (Carceller et al., 2011). However, it is common for radioiodine treatment to cause damage to the thyroid, which decreases hormone levels (Carceller et al., 2011). Patients who have this reaction may develop hypothyroidism (Carceller et al., 2011).

Furthermore, surgical treatment is also an option for patients with GD, specifically those who are younger, have high hormone levels, and have developed a goiter (Nystrom, 2011). This method of treatment involves removing part of the thyroid and replacing T4 (Gaffud, Lee, Solorzano, Prinz, &Weber, 2006). The surgical procedure limits the reoccurrence significantly, but may result in complications such as injury to the thyroid gland and surrounding areas (Gaffud, Lee, Solorzano, Prinz, &Weber, 2006). This procedure may also result in hypothyroidism (Gaffud, Lee, Solorzano, Prinz, &Weber, 2006).

Summary and Conclusion

GD is an autoimmune disease that was first discovered by Robert Graves in 1835 and is currently the most prevalent diagnosis of hyperthyroidism (Weeks, 2005; Nystrom, 2011). This disease directly impacts the functioning of the thyroid gland, as a result of autoantibodies binding to the TSH receptor, which inhibits the signal to the thyroid to stop producing hormones (Micheals, 2011). Because this negative feedback is inhibited, there is a significant increase the amount of T4 and T3 the gland produces (Mokhasi et al., 2012).

There are multiple factors involved in the development of GD, including both genetic and environmental factors (Bahn, Davies, Latif & Yin, 2012). Numerous studies have demonstrated a connection between a specific genotype and GD (Bahn, Davies, Latif & Yin, 2012). Additionally, factors associated with stress (Effraimidis, Tijssen, Brosschot, & Wiersinga, 2012), smoking, certain medications, and specific viruses can also result in GD by triggering a physiological chain of events that impacts hinders the inhibition of the release of thyroid hormones (Dalan & Leow, 2012). This epigenetic combination typically results in symptoms related to anxiety, the presence of goiter (Weeks, 2005), ophthalmopathy, (Bednarek, Wysocki, & Sowiñski, 2005) pretibial myxedema (Houck, Kauffman, Missner & Ramsay, 1998), and acropachy (Nystrom, 2011).

GD may be diagnosed by a physician after a thorough exam and supplemental blood tests (Weeks, 2005). There are three common treatment strategies used to target the release of thyroid hormones, including antithyroid medications, radioactive iodine, and surgery (Weeks, 2005). Undoubtedly, GD is a complex disease that could have a significant impact on one's life (Weeks, 2005). Fortunately, current treatment protocols have been demonstrated to be effective with most individuals (Nystrom, 2011).