drugs, the hyperthyroid state may recur. the risk of recurrence is about 40–50%, and lifelong treatment with antithyroid drugs carries some side effects such as agranulocytosis and liver disease. side effects of the antithyroid medications include a potentially fatal reduction in the level of white blood cells. therapy with radioiodine is the most common treatment in the united states, while antithyroid drugs and/or thyroidectomy are used more often in europe, japan, and most of the rest of the world. β-blockers (such as propranolol) may be used to inhibit the sympathetic nervous system symptoms of tachycardia and nausea until antithyroid treatments start to take effect. pure β-blockers do not inhibit lid retraction in the eyes, which is mediated by alpha adrenergic receptors. antithyroid drugs the main antithyroid drugs are carbimazole (in the uk), methimazole (in the us), and propylthiouracil/ptu. these drugs block the binding of iodine and coupling of iodotyrosines. the most dangerous side effect is agranulocytosis (1/250, more in ptu). others include granulocytopenia (dose-dependent, which improves on cessation of the drug) and aplastic anemia. patients on these medications should see a doctor if they develop sore throat or fever. the most common side effects are rash and peripheral neuritis. these drugs also cross the placenta and are secreted in breast milk. lugol's iodine may be used to block hormone synthesis before surgery. a randomized control trial testing single-dose treatment for graves' found methimazole achieved euthyroid state more effectively after 12 weeks than did propylthyouracil (77.1% on methimazole 15 mg vs 19.4% in the propylthiouracil 150 mg groups). no difference in outcome was shown for adding thyroxine to antithyroid medication and continuing thyroxine versus placebo after antithyroid medication withdrawal. however, two markers were found that can help predict the risk of recurrence. these two markers are a positive tshr antibody (tshr-ab) and smoking. a positive tshr-ab at the end of antithyroid drug treatment increases the risk of recurrence to 90% (sensitivity 39%, specificity 98%), and a negative tshr-ab at the end of antithyroid drug treatment is associated with a 78% chance of remaining in remission. smoking was shown to have an impact independent to a positive tshr-ab. radioiodine scan of affected thyroid before (top) and after (bottom) radioiodine therapy radioiodine (radioactive iodine-131) was developed in the early 1940s at the mallinckrodt general clinical research center. this modality is suitable for most patients, although some prefer to use it mainly for older patients. indications for radioiodine are failed medical therapy or surgery and where medical or surgical therapy are contraindicated. hypothyroidism may be a complication of this therapy, but may be treated with thyroid hormones if it appears. the rationale for radioactive iodine is that it accumulates in the thyroid and irradiates the gland with its beta and gamma radiations, about 90% of the total radiation being emitted by the beta (electron) particles. the most common method of iodine-131 treatment is to administer a specified amount in microcuries per gram of thyroid gland based on palpation or radiodiagnostic imaging of the gland over 24 hours. patients who receive the therapy must be monitored regularly with thyroid blood tests to ensure they are treated with thyroid hormone before they become symptomatically hypothyroid. contraindications to rai are pregnancy (absolute), ophthalmopathy (relative; it can aggravate thyroid eye disease), or solitary nodules. disadvantages of this treatment are a high incidence of hypothyroidism (up to 80%) requiring eventual thyroid hormone supplementation in the form of a daily pill(s). the radioiodine treatment acts slowly (over months to years) to destroy the thyroid gland, and graves' disease–associated hyperthyroidism is not cured in all persons by radioiodine, but has a relapse rate that depends on the dose of radioiodine which is administered. in rare cases, radiation induced thyroiditis has been linked to this treatment. surgery further information: thyroidectomy this modality is suitable for young and pregnant people. indications for thyroidectomy can be separated into absolute indications or relative indications. these indications aid in deciding which people would benefit most from surgery. the absolute indications are a large goiter (especially when compressing the trachea), suspicious nodules or suspected cancer (to pathologically examine the thyroid), and people with ophthalmopathy and additionally if it is the person's preferred method of treatment or if refusing to undergo radioactive iodine treatment. pregnancy is advised to be delayed for 6 months after radioactive iodine treatment. both bilateral subtotal thyroidectomy and the hartley-dunhill procedure (hemithyroidectomy on one side and partial lobectomy on other side) are possible. advantages are immediate cure and potential removal of carcinoma. its risks are injury of the recurrent laryngeal nerve, hypoparathyroidism (due to removal of the parathyroid glands), hematoma (which can be life-threatening if it compresses the trachea), relapse following medical treatment, infections (less common), and scarring. the increase in the risk of nerve injury can be due to the increased vascularity of the thyroid parenchyma and the development of links between the thyroid capsule and the surrounding tissues. reportedly, a 1% incidence exists of permanent recurrent laryngeal nerve paralysis after complete thyroidectomy. risks related to anesthesia are many, thus coordination with the anesthesiologist and patient optimization for surgery preoperatively are essential. removal of the gland enables complete biopsy to be performed to have definite evidence of cancer anywhere in the thyroid. (needle biopsies are not so accurate at predicting a benign state of the thyroid). no further treatment of the thyroid is required, unless cancer is detected. radioiodine uptake study may be done after surgery, to ensure all remaining (potentially cancerous) thyroid cells (i.e., near the nerves to the vocal cords) are destroyed. besides this, the only remaining treatment will be levothyroxine, or thyroid replacement pills to be taken for the rest of the patient's life. a 2013 review article concludes that surgery appears to be the most successful in the management of graves' disease, with total thyroidectomy being the preferred surgical option. eyes mild cases are treated with lubricant eye drops or nonsteroidal anti-inflammatory drops. severe cases threatening vision (corneal exposure or optic nerve compression) are treated with steroids or orbital decompression. in all cases, cessation of smoking is essential. double vision can be corrected with prism glasses and surgery (the latter only when the process has been stable for a while). difficulty closing eyes can be treated with lubricant gel at night, or with tape on the eyes to enable full, deep sleep. orbital decompression can be performed to enable bulging eyes to retreat back into the head. bone is removed from the skull behind the eyes, and space is made for the muscles and fatty tissue to fall back into the skull. eyelid surgery can be performed on upper and/or lower eyelids to reverse the effects of graves' disease on the eyelids. eyelid muscles can become tight with graves' disease, making it impossible to close the eyes all the way. eyelid surgery involves an incision along the natural crease of the eyelid, and a scraping away of the muscle that holds the eyelid open. this makes the muscle weaker, which allows the eyelid to extend over the eyeball more effectively. eyelid surgery helps reduce or eliminate dry eye symptoms. for management of clinically active graves' disease, orbitopathy (clinical activity score >2) with at least mild to moderate severity, intravenous glucocorticoids are the treatment of choice, usually administered in the form of pulse intravenous methylprednisolone. studies have consistently shown that pulse intravenous methylprednisolone is superior to oral glucocorticoids both in terms of efficacy and decreased side effects for managing graves' orbitopathy. prognosis if left untreated, more serious complications could result, including birth defects in pregnancy, increased risk of a miscarriage, bone mineral loss and, in extreme cases, death. graves' disease is often accompanied by an increase in heart rate, which may lead to further heart complications, including loss of the normal heart rhythm (atrial fibrillation), which may lead to stroke. if the eyes are proptotic (bulging) enough that the lids do not close completely at night, dryness will occur – with the risk of a secondary corneal infection, which could lead to blindness. pressure on the optic nerve behind the globe can lead to visual field defects and vision loss, as well. prolonged untreated hyperthyroidism can lead to bone loss, which may resolve when treated. epidemiology most common causes of hyperthyroidism by age graves' disease occurs in about 0.5% of people. graves' disease data has shown that the lifetime risk for women is around 3% and 0.5% for men. it occurs about 7.5 times more often in women than in men and often starts between the ages of 40 and 60. it is the most common cause of hyperthyroidism in the united states (about 50 to 80% of cases). history graves' disease owes its name to the irish doctor robert james graves, who described a case of goiter with exophthalmos in 1835. (medical eponyms are often styled nonpossessively; thus graves' disease and graves disease are variant stylings of the same term.) the german karl adolph von basedow independently reported the same constellation of symptoms in 1840. as a result, on the european continent, the terms "basedow syndrome", "basedow disease", or "morbus basedow" are more common than "graves' disease". graves' disease has also been called exophthalmic goiter. less commonly, it has been known as parry disease, begbie disease, flajan disease, flajani–basedow syndrome, and marsh disease. these names for the disease were derived from caleb hillier parry, james begbie, giuseppe flajani, and henry marsh. early reports, not widely circulated, of cases of goiter with exophthalmos were published by the italians giuseppe flajani and antonio giuseppe testa, in 1802 and 1810, respectively. prior to these, caleb hillier parry, a notable provincial physician in england of the late-18th century (and a friend of edward miller-gallus), described a case in 1786. this case was not published until 1825 - ten years ahead of graves. however, fair credit for the first description of graves' disease goes to the 12th century persian physician sayyid ismail al-jurjani, who noted the association of goiter and exophthalmos in his thesaurus of the shah of khwarazm, the major medical dictionary of its time. society and culture notable cases marty feldman used his bulging eyes, caused by graves' disease, for comedic effect. ayaka, japanese singer, was diagnosed with graves' disease in 2007. after going public with her diagnosis in 2009, she took a two-year hiatus from music to focus on treatment. susan elizabeth blow, american educator and founder of the first publicly funded kindergarten in the united states, was forced to retire and seek treatment for graves' disease in 1884. george h. w. bush, former u.s. president, developed new atrial fibrillation and was diagnosed in 1991 with hyperthyroidism due to the disease and treated with radioactive iodine. the president's wife, barbara bush, also developed the disease around the same time, which, in her case, produced severe infiltrative exophthalmos. rodney dangerfield, american comedian and actor gail devers, american sprinter: a doctor considered amputating her feet after she developed blistering and swelling following radiation treatment for graves' disease, but she went on to recover and win olympic medals. missy elliott, american hip-hop artist marty feldman, british comedy writer, comedian and actor sia, australian singer and songwriter sammy gravano, italian-american former underboss of the gambino crime family. jim hamilton, scottish rugby player, discovered he had graves' disease shortly after retiring from the sport in 2017. heino, german folk singer, whose dark sunglasses (worn to hide his symptoms) became part of his trademark look herbert howells, british composer; the first person to be treated with radium injections yayoi kusama, japanese artist. nadezhda krupskaya, russian communist and wife of vladimir lenin umm kulthum was an egyptian singer, songwriter, and film actress active from the 1920s to the 1970s. barbara leigh, an american former actress and fashion model, now spokeswoman for the national graves' disease foundation keiko masuda, japanese singer and one-half of the duo pink lady. yūko miyamura, japanese voice actress lord monckton, former ukip and conservative politician. sophia parnok, russian poet sir cecil spring rice, british ambassador to the united states during world war i, died suddenly of the disease in 1918. christina rossetti, english victorian-era poet dame maggie smith, british actress mary webb, british novelist and poet wendy williams, american tv show host act yasukawa, japanese professional wrestler. literature in italo svevo's novel zeno's conscience, character ada develops the disease. ern malley was