Grave's disease is an autoimmune condition which impacts the human thyroid gland. Excessive production of the thyroid hormone engorges the gland and it continues to grow. Because of this, there can be many adverse affects to the person's health, particularly in terms of ophthalmological and dermatological symptoms. The exact cause of the condition has not been determined nor has a cure for the disease. However, there are treatment methods available which can alleviate symptoms and even prevent further hyperthyroidism in the patients. Overview and Brief History of the Condition:

Grave's disease is an autoimmune disorder which most commonly affects the thyroid gland and results in hyperthyroidism, or over activity of the gland. Patients with this disease experience various symptoms but have a shared epidemiology. This condition creates antibodies which impact receptor activation within the thymus.

Causes:

The specific cause of Grave's disease is as yet unknown; however there are theories as to what might be the potential reasons why people develop this disease. There is a strong hereditary link associated with Grave's disease. Certain genetic markers have been shown to indicate whether someone develops the condition, including TSH receptors which activate the antibodies. HLA (human leukocyte antigen) DR also plays an important role in Grave's disease acquisition (Tomer 1993,-page 111).

Grave's disease occurs in females far more often than in males at a rate of approximately 5:1 or even 10:1 according to differing statistics. Approximately 2% of the female population will be affected by the condition at some point in their lives with the majority of patients being diagnosed later in life. Due to the fact that it often appears later in life, some researchers have suggested that the condition may be caused by an infection of some kind which then impacts the antibodies which react with Thyroid Stimulating Hormone (TSH) receptors. TSH, also known as thyrotopin, is released by the pituitary gland when the brain registers high levels of thyroid hormone in the bloodstream, which is in turn caused by hyperthyroidism. When a thyroid stimulating hormone becomes attached to a TSH receptor on a gland, the gland will continue to grow and will in turn produce even more of the hormone. If the TSI keeps stimulating the gland and the gland continues to produce the hormone despite normal levels already being reached, then the patient is diagnosed with Grave's disease.

Signs and Symptoms:

In addition, patients will show signs of hyperthyroid symptoms, such as increased speed of the heartbeat, muscle weaknesses, disturbed sleep, and increased irritability. Grave's diseases can cause difficulty for the heart, and problems with the circulatory or nervous systems. Due to the hypothyroidism of the condition, patients will also show such symptoms as: insomnia, hand tremors and other shaking, hair loss, hyperactivity, excessive sweating, itching, and intolerance to both heat and cold (Agabegi 2008,-page 157). Patients may also exhibit dietary and digestive issues including increased appetite with unexplainable weight loss, as well as diarrhea or frequent bowel movements.

There are psychological and emotional issues which are common with patients who have Grave's disease. Personality difficulties and quick changes in emotion are some of the negative mental aspects of the condition. Hyperthyroidism can result in depression, psychosis, anxiety, agitation, and even manic behaviors (Bunevicius 2006,-page 898).

Pathophysiology:

Grave's disease is an autoimmune condition. The body produces antibodies and they negatively impact the TSH receptor. They might also produce antibodies impacting thyroglobulin or specific thyroid hormones. The antibodies which are made create hyperthyroidism because the TSH receptor becomes bound to them. TSH receptors may be affected by types of antibodies (Abs) which are classified as stimulating, blocking, or neutral (Morshed 2010,-page 5537). There are three types of autoantibodies which react with the TSH reactor, including thyroid stimulating immunoglobulins (TSI), thyroid growth immunoglobulins (TGI), and thyrotrophin binding-inhibiting immunoglobulins (TBII) (Bunevicius 2006,-page 900). TSI creates an elevated production of the thyroid hormone. TSI bond directly to the TSH reactor and have been shown to grow the thyroid follicles. Finally TBII prevents TSH and its receptor from functioning properly. Hyperthyroidism then causes the thyroid gland to enlarge which begins the course of other negative issues associated with the condition. It has been suggested by some researchers that the bulging of the eye associated with Grave's disease, also known as exophthalmos, might be caused by a shared antigen between the antibodies and the muscles surrounding the eye. If the antigen is related,...

al who discovered that each of the pertinent antibodies related to TSH had a unique epitope pattern (2012). Such epitopes were distinct however they had similar characteristics in that they contacted the "hinge region and the amino terminus of the TSHR following the signal peptide and encompassing cysteine box 1 which has previously shown to be important for TSH binding and activation" (Latif 2012). The distinctiveness of the various epitopes indicated their potential to impact the TSH and ultimately directly affected the propensity to be diagnosed with Grave's disease. Research in Grave's diseases has indicated beyond reasonable doubt that the condition has a direct correlation to antibodies and the TSH receptor. It is possible that soon research will be able to indicate exactly what alleviates and exacerbates symptomology, such as that conducted by Morshed et. al (2010) which shows oxidative stress markers may be the key to fully understanding the pathology of the disease (page 5537).
Scientists have been able to prove that those who have been diagnosed with Grave's disease are likely to experience bone loss because of osteoporosis. Any hyperthyroid condition can result in such bone loss. It is believed that more calcium and phosphorus is lost via the body's waste removal systems than should be and therefore the body is not receiving as much of these chemicals as is necessary for the body to perform correctly (Mathur 2006). If left untreated, thyrotoxicosis can set in which changes the levels of calcium in the body to perhaps even ae of its proper levels. The result can be even worse dietary and digestive problems, with increased urination and defecation and the potential of damage done to the kidneys and other components of the waste removal organs of the body.

Manifestations:

When Grave's disease is suspected, the thyroid will be enlarged, sometimes to twice its normal size, called a goiter. The thyroid will most often become overactive which can create other health problems. The most common manifestation of Grave's disease will by hyperthyroidism with diffuse goiter ophthalmology and dermopathy.

Ophthalmologically, patients may show signs of "lid lag" which is an inability to control the movement of the eye lid and makes the eyes appear droopy or tired. They might also have excessive tear production called lacrimation (Agabegi 2008,-page 157). One of the most obvious indications of Grave's disease is a bulging of the eyes, known as exophthalmos. When exophthalmos occurs, the eyes appear to bulge out of their sockets abnormally so that a large amount of the eyeball is exposed. The extraocular muscles and orbital fat are affected by the thyroid's inflammation. Other ocular manifestations of Grave's disease can include: soft tissue damage, enlargement of one or both of the eyes which makes them protrude out of the socket which a symptom is called proptosis, exposure of the corneas, and compression of the optic nerves (Khoo 2007,-page 1014). There are six classifications of Grave's disease related optical disease and they are as follows: Class 0 which is no symptom of eye disease, Class 1 where signs are limited to lid retraction or staring, Class 2 which damages the soft tissues, Class 3 where proptosis occurs, Class 4 which involved extraocular muscles, Class 5 where the cornea is damaged, and finally Class 6 which results in loss of vision altogether (Cawood 2004,-page 385).

The dermatological manifestation of Grave's disease includes irritation of the skin which is called pretibial myxedema which is caused by the autoimmune component of the condition. When a person has Grave's disease, then they might have a skin irritation which is associated with it. Usually, the skin takes on a reddish or orange tint and a rough texture, providing the symptom with the nickname "orange peel" skin. Lumps or lesions are also visible on the skin, usually on the limbs and torso. In a study conducted by Schwartz and colleagues (2002), it was found that the majority of patients who developed thyroid dermopathy would most often experience skin irritation in pretibial areas (page 438). They also found that those who had dermopathy would almost always also be affected by ophthalmopathy at a staggering 97% of those involved in the study.

Possible Treatments:

Although there is no outright cure for Grave's disease at present, there are proven techniques which treat the disease and make it manageable for the patient. Catching it early on and treating it as soon as possible also ensure that the more damaging effects of the condition, such as the eye protrusion and the osteoporosis…