Grave's Disease

Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones (a serious metabolic imbalance known as hyperthyroidism and thyrotoxicosis). This is caused by thyroid autoantibodies that activate the TSH-receptor, thereby stimulating thyroid hormone synthesis and secretion, and thyroid growth (causing a diffusely enlarged goiter). The resulting state of hyperthyroidism can cause a dramatic constellation of neuropsychological and physical signs and symptoms.

Graves' disease is the most common cause of hyperthyroidism (60-90% of all cases), and usually presents itself during midlife, but also appears in children, adolescents, and the elderly. It has a powerful hereditary component, affects up to 2% of the female population, and is between five and ten times as common in females as in males. Graves’ disease is also the most common cause of severe hyperthyroidism, which is accompanied by more clinical signs and symptoms and laboratory abnormalities as compared with milder forms of hyperthyroidism. About 30-50% of people with Graves' disease will also suffer from Graves' ophthalmopathy (a protrusion of one or both eyes), caused by inflammation of the eye muscles by attacking autoantibodies.

Diagnosis is usually made on the basis of symptoms, although thyroid hormone tests may be useful. Graves’ thyrotoxicosis frequently builds over an extended period, sometimes years, before being diagnosed. This is partially because symptoms can develop so insidiously, they go unnoticed; when they do get reported, they are often confused with other health problems. Thus, diagnosing thyroid disease clinically can be challenging. Nevertheless, patients can experience a wide range of symptoms and suffer major impairment in most areas of health-related quality of life.

Graves’ disease has no cure, but treatments for its consequences (hyperthyroidism, ophthalmopathy, and mental symptoms) are available. The Graves’ disease itself - as defined, for example, by high serum thyroid autoantibodies (TSHR-Ab) concentrations or ophthalmopathy - often persists after its hyperthyroidism has been successfully treated.

The hyperthyroidism from Graves' disease causes a wide variety of symptoms. The two signs are truly 'diagnostic' of Graves' disease (i.e., not seen in other hyperthyroid conditions), exophthalmos (protuberance of one or both eyes) and pretibial myxedema, a rare skin disorder with an occurrence rate of 1-4%, that causes lumpy, reddish skin on the lower legs. Graves' disease also causes goitre (a diffuse enlargement of the thyroid gland). Though it also occurs with other causes of hyperthyroidism, Graves' disease is the most common cause of diffuse goitre. A large goitre is visible to the naked eye, but a smaller goitre may be detectable only by a physical exam. On occasion, goitre is not clinically detectable, but may be seen only with CT or ultrasound examination of the thyroid.

Differentiating Graves' hyperthyroidism from the other causes (thyroiditis, toxic multinodular goiter, toxic thyroid nodule, and excess thyroid hormone supplementation) is important to determine proper treatment. Thus, when hyperthyroidism is confirmed, or when blood results are inconclusive, thyroid antibodies should be measured (almost all patients with Graves' hyperthyroidism have detectable TSHR-Ab levels). Measurement of thyroid-stimulating immunoglobulin (TSI) is the most accurate measure of thyroid antibodies. They will be positive in 60 to 90% of children with Graves' disease. If TSI is not elevated, then a radioactive iodine uptake should be performed; an elevated result with a diffuse pattern is typical of Graves' disease. Biopsy to obtain histological testing is not normally required, but may be obtained if thyroidectomy is performed.