Graves disease

Definition
Grave’s disease is an autoimmune disorder that leads to over activity of the thyroid gland (hyperthyroidism). Grave’s disease is the leading cause of hyperthyroidism.

Pathophysiology
Grave’s disease is a form of type II hypersensitivity where the immune system makes antibodies called thyroid-stimulating immunoglobin (TSI) that attach to thyroid cells and mimic the actions of thyroid stimulating hormone and stimulate the thyroid to make too much thyroid hormone. The TSI stimulation of TSH receptors in the gland result in hyperplasia or goiter and also increased synthesis of thyroid hormone and especially triiodothyronine (T3). An overabundance of thyroid hormones affect all of the physiologic system such as metabolism, heart function, nervous system, body temperature and more. The two main manifestations of Grave’s disease are opthalmopathy and pretibial myxedema. Opthalmopathy results from hyperactivity of the autonomic nervous system which causes a lag of the globe or lid of the eye causing either an upward or downward gaze. Exophthalmos is caused by infiltrative changes caused by TSH receptor autoantibodies reacting with orbital fibroblast receptors which causes inflammation and edema of orbital contents. Individuals may also experience double vision caused by weakness to the extraocular muscles. Pretibial myxedema is subcutaneous swelling on the anterior portions of the legs and are indurated and erythematous skin. It is caused by thyrotropin receptor antigens on fibroblasts and recruited T lymphocyte that stimulate excess amounts of hyaluronic acid production in the dermis and subcutis.

Genetics
Exact cause of Grave’s disease is not known however genetic factors interacting with environmental factors play a role in the pathogenesis of this disease.

Epidemiology
Grave’s disease is most common in women under 40 years old. People with a family history of Grave’s disease or history of other autoimmune diseases have a higher risk of developing Grave’s disease.

Disease Described
People with Graves’ disease will likely present with some or all of the following symptoms. Exophthalmos and pretibial myxedema are significant for Graves’ disease. The patient would also likely have decreased TSH and elevated T3 and T4 levels. Patients may also present with a goiter and a bruit may be able to be heard over the goiter.

Signs and Symptoms

 * Exophthalmos
 * Myxedema
 * Nervousness or irritability
 * Fatigue
 * Muscle weakness
 * Heat intolerance
 * Rapid/Irregular heartbeat
 * Hand tremors
 * Weight loss
 * Goiter

Diagnosis
Diagnosis is based on physical exam and history looking for above signs and symptoms. Lab tests that would be ordered would be TSH, T3, T4, Radioactive iodine uptake test, TSI test. Diagnostic tests would also include a thyroid scan.

Treatment
Treatment is aimed at controlling the overactive thyroid. Treatment options are radioiodine therapy, antithyroid medication such as Tapazole, or surgery as a final option.

Links
[PubMed] [American Thyroid Association] [National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK] [Graves' Disease and Thyroid Foundation]

Related Articles
Management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Retrieved from http://www.guideline.gov/content.aspx?id=36623&search=grave%27s+disease Laboratory Science, 26(2). 112-117
 * National Clearinghouse Guidelines. (2011). Hyperthyroidism and other causes of thyrotoxicosis:
 * Chiasera, J. M. (2013). Back to the basics: Thyroid gland structure, function and pathology. Clinical