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Hyperthyroidism

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Hyperthyroidism
Other namesOveractive thyroid, hyperthyreosis
Triiodothyronine(T3,pictured) andthyroxine(T4) are both forms ofthyroid hormone.
SpecialtyEndocrinology
SymptomsIrritability, muscle weakness, sleeping problems,fast heartbeat,heat intolerance,diarrhea,enlargement of the thyroid,weight loss[1]
ComplicationsThyroid storm[2]
Usual onset20–50 years old[2]
CausesGraves' disease,multinodular goiter,toxic adenoma,inflammation of the thyroid,eating too muchiodine,too muchsynthetic thyroid hormone[1][2]
Diagnostic methodBased on symptoms and confirmed byblood tests[1]
TreatmentRadioiodine therapy,medications, thyroid surgery[1]
MedicationBeta blockers,methimazole[1]
Frequency1.2% (US)[3]
DeathsRare directly, unlessthyroid stormoccurs; associated with increased mortality if untreated (1.23HR)[4]

Hyperthyroidismis the condition that occurs due to excessive production ofthyroid hormonesby thethyroid gland.[3]Thyrotoxicosisis the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism.[3]Some, however, use the terms interchangeably.[5]Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, afast heartbeat,heat intolerance,diarrhea,enlargement of the thyroid,handtremor,andweight loss.[1]Symptoms are typically less severe in the elderly and duringpregnancy.[1]An uncommon but life-threatening complication isthyroid stormin which an event such as aninfectionresults in worsening symptoms such as confusion and ahigh temperature;this often results in death.[2]The opposite ishypothyroidism,when the thyroid gland does not make enough thyroid hormone.[6]

Graves' diseaseis the cause of about 50% to 80% of the cases of hyperthyroidism in the United States.[1][7]Other causes includemultinodular goiter,toxic adenoma,inflammation of the thyroid,eating too muchiodine,and too muchsynthetic thyroid hormone.[1][2]A less common cause is apituitary adenoma.[1]The diagnosis may be suspected based on signs and symptoms and then confirmed with blood tests.[1]Typically blood tests show a lowthyroid stimulating hormone(TSH) and raisedT3orT4.[1]Radioiodineuptake by the thyroid,thyroid scan,and measurement ofantithyroid autoantibodies(thyroidal thyrotropin receptor antibodies are positive in Graves disease) may help determine the cause.[1]

Treatment depends partly on the cause and severity of disease.[1]There are three main treatment options:radioiodine therapy,medications, and thyroid surgery.[1]Radioiodine therapy involves takingiodine-131by mouth which is then concentrated in and destroys the thyroid over weeks to months.[1]The resulting hypothyroidism is treated with synthetic thyroid hormone.[1]Medications such asbeta blockersmay control the symptoms, andanti-thyroid medicationssuch asmethimazolemay temporarily help people while other treatments are having an effect.[1]Surgery to remove the thyroid is another option.[1]This may be used in those with very large thyroids or when cancer is a concern.[1]In the United States hyperthyroidism affects about 1.2% of the population.[3]Worldwide, hyperthyroidism affects 2.5% of adults.[8]It occurs between two and ten times more often in women.[1]Onset is commonly between 20 and 50 years of age.[2]Overall the disease is more common in those over the age of 60 years.[1]

Signs and symptoms

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Hyperthyroidism may be asymptomatic or present with significant symptoms.[2]Some of the symptoms of hyperthyroidism include nervousness, irritability, increased perspiration, heart racing, hand tremors, anxiety,trouble sleeping,thinning of the skin, fine brittle hair, and muscular weakness—especially in the upper arms and thighs. More frequent bowel movements may occur, and diarrhea is common. Weight loss, sometimes significant, may occur despite a good appetite (though 10% of people with a hyperactive thyroid experience weight gain), vomiting may occur, and, for women, menstrual flow may lighten and menstrual periods may occur less often, or with longer cycles than usual.[9][10]

Exophthalmosseen inGraves ophthalmopathy

Thyroid hormone is critical to normal function of cells. In excess, it both overstimulatesmetabolismand disrupts the normal functioning ofsympathetic nervous system,causing "speeding up" of various body systems and symptoms resembling an overdose ofepinephrine(adrenaline). These include fast heartbeat and symptoms ofpalpitations,nervous systemtremorsuch as of the hands andanxietysymptoms, digestive systemhypermotility,unintended weight loss, and, inlipid panelblood tests, a lower and sometimes unusually low serumcholesterol.[11]

Major clinical signs of hyperthyroidism includeweight loss(often accompanied by an increasedappetite), anxiety,heat intolerance,hair loss (especially of the outer third of the eyebrows), muscle aches, weakness, fatigue, hyperactivity, irritability,high blood sugar,[11]excessive urination,excessive thirst,delirium,tremor,pretibial myxedema(inGraves' disease),emotional lability,and sweating.Panic attacks,inability to concentrate, andmemoryproblems may also occur.Psychosisandparanoia,common duringthyroid storm,are rare with milder hyperthyroidism. Many persons will experience complete remission of symptoms 1 to 2 months after aeuthyroidstate is obtained, with a marked reduction in anxiety, sense of exhaustion, irritability, and depression. Some individuals may have an increased rate of anxiety or persistence ofaffectiveand cognitive symptoms for several months to up to 10 years after a euthyroid state is established.[12]In addition, those with hyperthyroidism may present with a variety of physical symptoms such aspalpitationsandabnormal heart rhythms(the notable ones beingatrial fibrillation), shortness of breath (dyspnea), loss oflibido,amenorrhea,nausea,vomiting,diarrhea,gynecomastiaandfeminization.[13]Long term untreated hyperthyroidism can lead toosteoporosis.These classical symptoms may not be present often in the elderly.[14]

Bone loss, which is associated with overt but not subclinical hyperthyroidism, may occur in 10 to 20% of patients. This may be due to an increase in bone remodelling and a decrease in bone density, and increases fracture risk. It is more common in postmenopausal women; less so in younger women, and men. Bone disease related to hyperthyroidism was first described by Frederick von Recklinghausen, in 1891; he described the bones of a woman who died of hyperthyroidism as appearing "worm-eaten".[15]

Neurological manifestations can includetremors,chorea,myopathy,and in some susceptible individuals (in particular of Asian descent)periodic paralysis.An association between thyroid disease andmyasthenia gravishas been recognized. Thyroid disease, in this condition, isautoimmunein nature and approximately 5% of people with myasthenia gravis also have hyperthyroidism. Myasthenia gravis rarely improves after thyroid treatment and the relationship between the two entities is becoming better understood over the past 15 years.[16][17][18]

Illustration depicting enlarged thyroid that may be associated with hyperthyroidism

InGraves' disease,ophthalmopathymay cause the eyes to look enlarged because the eye muscles swell and push the eye forward. Sometimes, one or both eyes may bulge. Some have swelling of the front of the neck from an enlarged thyroid gland (a goiter).[19]

Minor ocular (eye) signs, which may be present in any type of hyperthyroidism, are eyelid retraction ( "stare" ),extraocular muscleweakness, andlid-lag.[20]In hyperthyroidstare(Dalrymple sign) the eyelids are retracted upward more than normal (the normal position is at the superiorcorneoscleral limbus,where the "white" of the eye begins at the upper border of the iris). Extraocular muscle weakness may present with double vision. In lid-lag (von Graefe's sign), when the person tracks an object downward with their eyes, the eyelid fails to follow the downward moving iris, and the same type of upper globe exposure which is seen with lid retraction occurs, temporarily. These signs disappear with treatment of the hyperthyroidism.[citation needed]

Neither of these ocular signs should be confused withexophthalmos(protrusion of the eyeball), which occurs specifically and uniquely in hyperthyroidism caused by Graves' disease (note that not all exophthalmos is caused by Graves' disease, but when present with hyperthyroidism is diagnostic of Graves' disease). This forward protrusion of the eyes is due to immune-mediated inflammation in the retro-orbital (eye socket) fat. Exophthalmos, when present, may exacerbate hyperthyroid lid-lag and stare.[21]

Thyroid storm

[edit]

Thyroid storm is a severe form of thyrotoxicosis characterized by rapid and oftenirregular heart beat,high temperature, vomiting, diarrhea, and mental agitation. Symptoms may not be typical in the young, old, or pregnant.[2]It usually occurs due to untreated hyperthyroidism and can be provoked by infections.[2]It is amedical emergencyand requires hospital care to control the symptoms rapidly. The mortality rate in thyroid storm is 3.6-17%, usually due to multi-organ system failure.[8]

Hypothyroidism

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Hyperthyroidism due to certain types ofthyroiditiscan eventually lead tohypothyroidism(alackof thyroid hormone), as the thyroid gland is damaged. Also,radioiodinetreatment of Graves' disease often eventually leads to hypothyroidism. Such hypothyroidism may be diagnosed with thyroid hormone testing and treated by oral thyroid hormone supplementation.[22]

Causes

[edit]
Most common causes of hyperthyroidism by age.[23]

There are several causes of hyperthyroidism. Most often, the entire gland is overproducing thyroid hormone. Less commonly, a single nodule is responsible for the excess hormone secretion, called a "hot" nodule. Thyroiditis (inflammation of the thyroid) can also cause hyperthyroidism.[24]Functional thyroid tissue producing an excess of thyroid hormone occurs in a number of clinical conditions.

The major causes in humans are:

  • Graves' disease.An autoimmune disease (usually, the most common cause with 50–80% worldwide, although this varies substantially with location- i.e., 47% in Switzerland (Horst et al., 1987) to 90% in the USA (Hamburger et al. 1981)). Thought to be due to varying levels of iodine in the diet.[25]It is eight times more common in females than males and often occurs in young females, around 20 to 40 years of age.[citation needed]
  • Toxic thyroid adenoma(the most common cause in Switzerland, 53%, thought to be atypical due to a low level of dietary iodine in this country)[25]
  • Toxic multinodular goiter[citation needed]

High blood levels of thyroid hormones (most accurately termedhyperthyroxinemia) can occur for a number of other reasons:

  • Inflammationof the thyroid is calledthyroiditis.There are several different kinds of thyroiditis includingHashimoto's thyroiditis(Hypothyroidism immune-mediated), andsubacute thyroiditis(de Quervain's). These may beinitiallyassociated with secretion of excess thyroid hormone but usually progress to gland dysfunction and, thus, to hormone deficiency and hypothyroidism.
  • Oral consumption of excess thyroid hormone tablets is possible (surreptitious use of thyroid hormone), as is the rare event of eating ground beef or pork contaminated with thyroid tissue, and thus thyroid hormones (termedhamburger thyrotoxicosisoralimentary thyrotoxicosis).[26]Pharmacy compounding errors may also be a cause.[27]
  • Amiodarone,anantiarrhythmic drug,is structurally similar to thyroxine and may cause either under-oroveractivityof the thyroid.[citation needed]
  • Postpartum thyroiditis(PPT) occurs in about 7% of women during the year after they give birth. PPT typically has several phases, the first of which is hyperthyroidism. This form of hyperthyroidism usually corrects itself within weeks or months without the need for treatment.
  • Astruma ovariiis a rare form of monodermalteratomathat contains mostly thyroid tissue, which leads to hyperthyroidism.
  • Excess iodine consumption notably from algae such askelp.

Thyrotoxicosis can also occur after taking too much thyroid hormone in the form of supplements, such aslevothyroxine(a phenomenon known as exogenous thyrotoxicosis,alimentarythyrotoxicosis, oroccultfactitial thyrotoxicosis).[28]

Hypersecretion ofthyroid stimulating hormone(TSH), which in turn is almost always caused by apituitary adenoma,accounts for much less than 1 percent of hyperthyroidism cases.[29]

Diagnosis

[edit]

Measuring the level ofthyroid-stimulating hormone(TSH), produced by the pituitary gland (which in turn is also regulated by the hypothalamus's TSH Releasing Hormone) in the blood is typically the initial test for suspected hyperthyroidism. A low TSH level typically indicates that the pituitary gland is being inhibited or "instructed" by the brain to cut back on stimulating the thyroid gland, having sensed increased levels of T4and/or T3in the blood. In rare circumstances, a low TSH indicates primary failure of the pituitary, or temporary inhibition of the pituitary due to another illness (euthyroid sick syndrome) and so checking the T4and T3is still clinically useful.[11]

Measuring specificantibodies,such as anti-TSH-receptor antibodies in Graves' disease, or anti-thyroid peroxidase inHashimoto's thyroiditis—a common cause ofhypothyroidism—may also contribute to the diagnosis. The diagnosis of hyperthyroidism is confirmed by blood tests that show a decreased thyroid-stimulating hormone (TSH) level and elevated T4and T3levels. TSH is a hormone made by the pituitary gland in the brain that tells the thyroid gland how much hormone to make. When there is too much thyroid hormone, the TSH will be low. A radioactive iodine uptake test and thyroid scan together characterizes or enables radiologists and doctors to determine the cause of hyperthyroidism. The uptake test uses radioactive iodine injected or taken orally on an empty stomach to measure the amount of iodine absorbed by the thyroid gland. Persons with hyperthyroidism absorb much more iodine than healthy persons which includes radioactive iodine which is easy to measure. A thyroid scan producing images is typically conducted in connection with the uptake test to allow visual examination of the over-functioning gland.[11]

Thyroidscintigraphyis a useful test to characterize (distinguish between causes of) hyperthyroidism, and this entity from thyroiditis. This test procedure typically involves two tests performed in connection with each other: aniodine uptake testand a scan (imaging) with agamma camera.The uptake test involves administering a dose of radioactive iodine (radioiodine), traditionallyiodine-131(131I), and more recentlyiodine-123(123I).Iodine-123may be the preferred radionuclide in some clinics due to its more favorable radiationdosimetry(i.e. less radiation dose to the person per unit administered radioactivity) and a gamma photon energy more amenable to imaging with thegamma camera.For the imaging scan, I-123 is considered an almost ideal isotope of iodine for imaging thyroid tissue and thyroid cancer metastasis.[30]Thyroid scintigraphy should not be performed in those who are pregnant, a thyroid ultrasound with color flow doppler may be obtained as an alternative in these circumstances.[8]

Typical administration involves a pill or liquid containing sodium iodide (NaI) taken orally, which contains a small amount ofiodine-131,amounting to perhaps less than a grain of salt. A 2-hour fast of no food prior to and for 1 hour after ingesting the pill is required. This low dose of radioiodine is typically tolerated by individuals otherwise allergic to iodine (such as those unable to tolerate contrast mediums containing larger doses of iodine such as used inCT scan,intravenous pyelogram(IVP), and similar imaging diagnostic procedures). Excess radioiodine that does not get absorbed into the thyroid gland is eliminated by the body in urine. Some people with hyperthyroidism may experience a slight allergic reaction to the diagnostic radioiodine and may be given anantihistamine.[citation needed]

The person returns 24 hours later to have the level of radioiodine "uptake" (absorbed by the thyroid gland) measured by a device with a metal bar placed against the neck, which measures the radioactivity emitting from the thyroid. This test takes about 4 minutes while the uptake % (i.e.,percentage) is accumulated (calculated) by the machine software. A scan is also performed, wherein images (typically a center, left and right angle) are taken of the contrasted thyroid gland with agamma camera;aradiologistwill read and prepare a report indicating the uptake % and comments after examining the images. People with hyperthyroid will typically "take up" higher than normal levels of radioiodine. Normal ranges for RAI uptake are from 10 to 30%.

In addition to testing the TSH levels, many doctors test for T3,Free T3,T4,and/or Free T4for more detailed results. Free T4is unbound to any protein in the blood. Adult limits for these hormones are: TSH (units): 0.45 – 4.50 uIU/mL; T4Free/Direct (nanograms): 0.82 – 1.77 ng/dl; and T3(nanograms): 71 – 180 ng/dl. Persons with hyperthyroidism can easily exhibit levels many times these upper limits for T4and/or T3.See a complete table of normal range limits for thyroid function at thethyroid glandarticle.

In hyperthyroidism CK-MB (Creatine kinase) is usually elevated.[31]

Subclinical

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In overt primary hyperthyroidism, TSH levels are low and T4and T3levels are high. Subclinical hyperthyroidism is a milder form of hyperthyroidism characterized by low or undetectable serum TSH level, but with a normal serum free thyroxine level.[32]Although the evidence for doing so is not definitive, treatment of elderly persons having subclinical hyperthyroidism could reduce the number of cases ofatrial fibrillation.[33]There is also an increased risk ofbone fractures(by 42%) in people with subclinical hyperthyroidism; there is insufficient evidence to say whether treatment with antithyroid medications would reduce that risk.[34]

A 2022 meta-analysis found subclinical hyperthyroidism to be associated with cardiovascular death.[35]

Screening

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In those without symptoms who are not pregnant there is little evidence for or against screening.[36]

Treatment

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Antithyroid drugs

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Thyrostatics (antithyroid drugs) are drugs that inhibit the production of thyroid hormones, such ascarbimazole(used in the UK) andmethimazole(used in the US, Germany and Russia), andpropylthiouracil.Thyrostatics are believed to work by inhibiting theiodinationofthyroglobulinbythyroperoxidaseand, thus, the formation of tetraiodothyronine (T4). Propylthiouracil also works outside the thyroid gland, preventing the conversion of (mostly inactive) T4to the active form T3.Because thyroid tissue usually contains a substantial reserve of thyroid hormone, thyrostatics can take weeks to become effective and the dose often needs to be carefully titrated over a period of months, with regular doctor visits and blood tests to monitor results.[11]

Beta-blockers

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Many of the common symptoms of hyperthyroidism such as palpitations, trembling, and anxiety are mediated by increases in beta-adrenergic receptors on cell surfaces.Beta blockers,typically used to treat high blood pressure, are a class of drugs that offset this effect, reducing rapid pulse associated with the sensation of palpitations, and decreasing tremor and anxiety. Thus, a person with hyperthyroidism can often obtain immediate temporary relief until the hyperthyroidism can be characterized with the Radioiodine test noted above and more permanent treatment take place. Note that these drugs do not treat hyperthyroidism or any of its long-term effects if left untreated, but, rather, they treat or reduce only symptoms of the condition.[37]

Some minimal effect on thyroid hormone production however also comes withpropranolol—which has two roles in the treatment of hyperthyroidism, determined by the different isomers of propranolol. L-propranolol causes beta-blockade, thus treating the symptoms associated with hyperthyroidism such as tremor, palpitations, anxiety, andheat intolerance.D-propranolol inhibits thyroxine deiodinase, thereby blocking the conversion of T4to T3,providing some though minimal therapeutic effect. Other beta-blockers are used to treat only the symptoms associated with hyperthyroidism.[38]Propranololin the UK, andmetoprololin the US, are most frequently used to augment treatment for people with hyperthyroid.[39]

Diet

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People with autoimmune hyperthyroidism (such as inGrave's disease) should not eat foods high in iodine, such asedible seaweedandseafood.[1]

From a public health perspective, the general introduction of iodized salt in the United States in 1924 resulted in lower disease, goiters, as well as improving the lives of children whose mothers would not have eaten enough iodine during pregnancy which would have lowered the IQs of their children.[40]

Surgery

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Surgery(thyroidectomyto remove the whole thyroid or a part of it) is not extensively used because most common forms of hyperthyroidism are quite effectively treated by the radioactive iodine method, and because there is a risk of also removing theparathyroid glands,and of cutting therecurrent laryngeal nerve,making swallowing difficult, and even simply generalizedstaphylococcalinfection as with any major surgery. Some people with Graves' may opt for surgical intervention. This includes those that cannot tolerate medicines for one reason or another, people that are allergic to iodine, or people that refuse radioiodine.[41]

A 2019systematic reviewconcluded that the available evidence shows no difference between visually identifying the nerve or utilizing intraoperativeneuroimagingduring surgery, when trying to prevent injury to recurrent laryngeal nerve during thyroid surgery.[42]

If people have toxic nodules treatments typically include either removal or injection of the nodule with alcohol.[43]

Radioiodine

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Iniodine-131(radioiodine)radioisotope therapy,which was first pioneered by Dr.Saul Hertz,[44]radioactive iodine-131 is given orally (either by pill or liquid) on a one-time basis, to severely restrict, or altogether destroy the function of a hyperactive thyroid gland. This isotope of radioactive iodine used for ablative treatment is more potent than diagnostic radioiodine (usuallyiodine-123or a very low amount of iodine-131), which has a biological half-life from 8–13 hours. Iodine-131, which also emits beta particles that are far more damaging to tissues at short range, has a half-life of approximately 8 days. People not responding sufficiently to the first dose are sometimes given an additional radioiodine treatment, at a larger dose. Iodine-131 in this treatment is picked up by the active cells in the thyroid and destroys them, rendering the thyroid gland mostly or completely inactive.[45]

Since iodine is picked up more readily (though not exclusively) by thyroid cells, and (more important) is picked up even more readily by over-active thyroid cells, the destruction is local, and there are no widespread side effects with this therapy. Radioiodine ablation has been used for over 50 years, and the only major reasons for not using it are pregnancy and breastfeeding (breast tissuealso picks up and concentrates iodine). Once the thyroid function is reduced, replacement hormone therapy (levothyroxine) taken orally each day replaces the thyroid hormone that is normally produced by the body.[46]

There is extensive experience, over many years, of the use of radioiodine in the treatment of thyroid overactivity and this experience does not indicate any increased risk of thyroid cancer following treatment. However, a study from 2007 has reported an increased number of cancer cases after radioiodine treatment for hyperthyroidism.[45]

The principal advantage of radioiodine treatment for hyperthyroidism is that it tends to have a much higher success rate than medications. Depending on the dose of radioiodine chosen, and the disease under treatment (Graves' vs. toxic goiter, vs. hot nodule etc.), the success rate in achieving definitive resolution of the hyperthyroidism may vary from 75 to 100%. A major expected side-effect of radioiodine in people with Graves' disease is the development of lifelonghypothyroidism,requiring daily treatment with thyroid hormone. On occasion, some people may require more than one radioactive treatment, depending on the type of disease present, the size of the thyroid, and the initial dose administered.[47]

People with Graves' disease manifesting moderate or severeGraves' ophthalmopathyare cautioned against radioactive iodine-131 treatment, since it has been shown to exacerbate existing thyroid eye disease. People with mild or no ophthalmic symptoms can mitigate their risk with a concurrent six-week course ofprednisone.The mechanisms proposed for this side effect involve a TSH receptor common to boththyrocytesand retro-orbital tissue.[48]

As radioactive iodine treatment results in the destruction of thyroid tissue, there is often a transient period of several days to weeks when the symptoms of hyperthyroidism may actually worsen following radioactive iodine therapy. In general, this happens as a result of thyroid hormones being released into the blood following the radioactive iodine-mediated destruction of thyroid cells that contain thyroid hormone. In some people, treatment with medications such asbeta blockers(propranolol,atenolol,etc.) may be useful during this period of time. Most people do not experience any difficulty after the radioactive iodine treatment, usually given as a small pill. On occasion, neck tenderness or a sore throat may become apparent after a few days, if moderate inflammation in the thyroid develops and produces discomfort in the neck or throat area. This is usually transient, and not associated with a fever, etc.[citation needed]

It is recommended that breastfeeding be stopped at least six weeks before radioactive iodine treatment and that it not be resumed, although it can be done in future pregnancies. It also shouldn't be done during pregnancy, and pregnancy should be put off until at least 6–12 months after treatment.[49][50]

A common outcome following radioiodine is a swing from hyperthyroidism to the easily treatable hypothyroidism, which occurs in 78% of those treated for Graves' thyrotoxicosis and in 40% of those with toxic multinodular goiter or solitary toxic adenoma.[51]Use of higher doses of radioiodine reduces the number of cases of treatment failure, with penalty for higher response to treatment consisting mostly of higher rates of eventual hypothyroidism which requires hormone treatment for life.[52]

There is increased sensitivity to radioiodine therapy in thyroids appearing onultrasound scansas more uniform (hypoechogenic), due to densely packed large cells, with 81% later becoming hypothyroid, compared to just 37% in those with more normal scan appearances (normoechogenic).[53]

Thyroid storm

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Thyroid stormpresents with extreme symptoms of hyperthyroidism. It is treated aggressively withresuscitationmeasures along with a combination of the above modalities including: an intravenous beta blockers such aspropranolol,followed by athioamidesuch asmethimazole,an iodinated radiocontrast agent or an iodine solution if the radiocontrast agent is not available, and an intravenoussteroidsuch ashydrocortisone.[54]Propylthiouracilis the preferred thioamide in thyroid storm as it can prevent the conversion of T4 to the more active T3 in the peripheral tissues in addition to inhibiting thyroid hormone production.[8]

Alternative medicine

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In countries such as China, herbs used alone or with antithyroid medications are used to treat hyperthyroidism.[55]Very low quality evidence suggests thattraditional Chinese herbal medicationsmay be beneficial when taken along with routine hyperthyroid medications, however, there is no reliable evidence to determine the effectiveness of Chinese herbal medications for treating hyperthyroidism.[55]

Epidemiology

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In the United States hyperthyroidism affects about 1.2% of the population.[3]About half of these cases have obvious symptoms while the other half do not.[2]It occurs between two and ten times more often in women.[1]The disease is more common in those over the age of 60 years.[1]

Subclinical hyperthyroidismmodestly increases the risk of cognitive impairment and dementia.[56]

History

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Caleb Hillier Parryfirst made the association between the goiter and protrusion of the eyes in 1786, however, did not publish his findings until 1825.[57]In 1835, Irish doctorRobert James Gravesdiscovered a link between the protrusion of the eyes and goiter, giving his name to the autoimmune disease now known as Graves' Disease.[citation needed]

Pregnancy

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Recognizing and evaluating hyperthyroidism in pregnancy is a diagnostic challenge.[58]Thyroid hormones are commonly elevated during the first trimester of pregnancy as the pregnancy hormonehuman chorionic gonadotropin(hCG) stimulates thyroid hormone production, in a condition known as gestational transient thyrotoxicosis.[8]Gestational transient thyrotoxicosis generally abates in the second trimester as hCG levels decline and thyroid function normalizes.[8]Hyperthyroidism can increase the risk of complications for mother and child.[59]Such risks include pregnancy-related hypertension, pregnancy loss, low-birth weight,pre-eclampsia,pretermdelivery, still birth and behavioral disorders later in the child's life.[8][60][59][61]Nonetheless, high maternal FT4 levels during pregnancy have been associated with impaired brain developmental outcomes of the offspring and this was independent of hCG levels.[62]

Propylthiouracil is the preferredantithyroidmedication in the 1st trimester of pregnancy as it is lessteratogenicthan methimazole.[8]

Other animals

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Cats

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Hyperthyroidism is one of the most common endocrine conditions affecting older domesticatedhousecats.In the United States, up to 10% of cats over ten years old have hyperthyroidism.[63]The disease has become significantly more common since the first reports of feline hyperthyroidism in the 1970s. The most common cause of hyperthyroidism in cats is the presence ofbenign tumorscalled adenomas. 98% of cases are caused by the presence of an adenoma,[64]but the reason these cats develop such tumors continues to be studied.

The most common presenting symptoms are: rapidweight loss,tachycardia(rapid heart rate),vomiting,diarrhea,increased consumption of fluids (polydipsia), increased appetite (polyphagia), and increased urine production (polyuria). Other symptoms include hyperactivity, possible aggression, an unkempt appearance, and large, thickclaws.Heart murmursand agallop rhythmcan develop due to secondaryhypertrophic cardiomyopathy.About 70% of affected cats also have enlarged thyroid glands (goiter). 10% of cats exhibit "apathetic hyperthyroidism", which is characterized by anorexia and lethargy.[65]

The same three treatments used with humans are also options in treating feline hyperthyroidism (surgery, radioiodine treatment, and anti-thyroid drugs). There is also a special low iodine diet available that will control the symptoms providing no other food is fed; Hill's y/d formula, when given exclusively, decreases T4 production by limiting the amount of iodine needed for thyroid hormone production. It is the only available commercial diet that focuses on managing feline hyperthyroidism. Medical and dietary management using methimazole and Hill's y/d cat food will give hyperthyroid cats an average of 2 years before dying due to secondary conditions such as heart and kidney failure.[65]Drugs used to help manage the symptoms of hyperthyroidism are methimazole and carbimazole. Drug therapy is the least expensive option, even though the drug must be administered daily for the remainder of the cat's life. Carbimazole is only available as a once daily tablet. Methimazole is available as an oral solution, a tablet, and compounded as atopical gelthat is applied using afinger cotto the hairless skin inside a cat's ear. Many cat owners find this gel a good option for cats that don't like being given pills.[citation needed]

Radioiodine treatment, however, is not available in all areas, as this treatment requires nuclear radiological expertise and facilities that not only board the cat, but are specially equipped to manage the cat's urine, sweat, saliva, and stool, which are radioactive for several days after the treatment, usually for a total of 3 weeks (the cat spends the first week in total isolation and the next two weeks in close confinement).[66]In the United States, the guidelines for radiation levels vary from state to state; some states such as Massachusetts allow hospitalization for as little as two days before the animal is sent home with care instructions.[citation needed]

Dogs

[edit]

Hyperthyroidism is much less common indogscompared to cats.[67]Hyperthyroidism may be caused by a thyroid tumor. This may be a thyroidcarcinoma.About 90% of carcinomas are very aggressive; they invade the surrounding tissues andmetastasize(spread) to other tissues, particularly the lungs. This has a poorprognosis.Surgery to remove the tumor is often very difficult due tometastasisintoarteries,theesophagus,or thewindpipe.It may be possible to reduce the size of the tumor, thus relieving symptoms and allowing time for other treatments to work.[citation needed]About 10% of thyroid tumors are benign; these often cause few symptoms.[citation needed]

In dogs treated forhypothyroidism(lack of thyroid hormone), iatrogenic hyperthyroidism may occur as a result of an overdose of the thyroid hormone replacement medication,levothyroxine;in this case, treatment involves reducing the dose of levothyroxine.[68][69]Dogs which displaycoprophagy,the consumption of feces, and also live in a household with a dog receiving levothyroxine treatment, may develop hyperthyroidism if they frequently eat the feces from the dog receiving levothyroxine treatment.[70]

Hyperthyroidism may occur if a dog eats an excessive amount of thyroid gland tissue. This has occurred in dogs fed commercial dog food.[71]

See also

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References

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