Hyperthyroidism

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Overview
Hyperthyroidism (or "overactive thyroid gland") is the clinical syndrome caused by an excess of circulating free thyroxine (T4) or free triiodothyronine (T3), or both.

Causes
Hyperthyroidism is the result of excess thyroid hormone production, causing an overactive metabolism and increased speed of all the body's processes. Thyroid hormone generally controls the pace of all of the processes in the body. This pace is called one's metabolism. If there is too much thyroid hormone, every function of the body tends to speed up. The thyroid gland regulates the body temperature by secreting two hormones that control how quickly the body burns calories and energy. If the thyroid produces too much hormone, the condition is called hyperthyroidism, but if too little is produced, the result is hypothyroidism.

Major causes in humans are:
 * Graves' disease (the most common etiology with 70-80%)
 * Toxic thyroid adenoma
 * Toxic multinodular goitre

Other causes of hyperthyroxinemia (high blood levels of thyroid hormones) are not to be confused with true hyperthyroidism and include subacute and other forms of thyroiditis (inflammation) and struma ovarii (a teratoma). Thyrotoxicosis (symptoms caused by hyperthyroxinemia) can occur in both hyperthyroidism and thyroiditis. When it causes acutely increased metabolism, it is sometimes called "thyroid storm", a life-threatening event characterized by tachycardia, hypertension, and fever.

Excess thyroid hormone from pills can also cause hyperthyroidism. Amiodarone, a heart medication, can sometimes cause hyperthyroidism. Hamburger toxicosis is a condition that occurs sporadically and is associated with ground beef contaminated with thyroid hormone.

Postpartum thyroiditis occurs in about 7% of women during the year after they give birth. PPT typically has several phases, the first of which is hyperthyroidism. Many times, the hyperthyroidism corrects itself within weeks or months without any treatment necessary.

Complete Differential Diagnosis of Hyperthyroidism

 * Amiodarone
 * Gestational thyrotoxicosis
 * Grave's Disease
 * Hashimoto's thyroiditis
 * HCG-secreting tumors
 * Iatrogenic factitious
 * Iodine excess
 * Metastatic differentiated thyroid cancer
 * Radiation thyroiditis
 * Reidel's thyroiditis
 * Silent thyroiditis
 * Struma ovarii
 * Subacute thyroiditis
 * Suppurative thyroiditis
 * Thyroid carcinoma
 * Thyroid hormone resistance syndrome
 * Toxic thyroid adenoma
 * Toxic multinodular goiter
 * TSH (thyroid stimulating hormone)-secreting pituitary adenoma

Signs and symptoms
Major clinical weight loss (often accompanied by a ravenous appetite), intolerance to heat, fatigue, weakness, hyperactivity, irritability, apathy, depression, polyuria, polydipsia, and sweating. Additionally, patients may present with a variety of symptoms such as palpitations and arrhythmias (notably atrial fibrillation), shortness of breath (dyspnea), loss of libido, nausea, vomiting, and diarrhea. In the elderly, these classical symptoms may not be present and they may present only with fatigue and weight loss leading to apathetic hyperthyroidism.

Neurological manifestations are tremor, chorea, myopathy, and periodic paralysis. Stroke of cardioembolic origin due to coexisting atrial fibrillation may be mentioned as one of the most serious complications of hyperthyroidism.

As to other autoimmune disorders related with thyrotoxicosis, an association between thyroid disease and myasthenia gravis has been well recognized. The thyroid disease, in this condition, is often an autoimmune one and approximately 5% of patients with myasthenia gravis also have hyperthyroidism. Myasthenia gravis rarely improves after thyroid treatment and the relationship between the two entities is as yet unknown. Some very rare neurological manifestations that are reported to be dubiously associated with thyrotoxicosis are pseudotumor cerebri, amyotrophic lateral sclerosis and a Guillain-Barré-like syndrome.

Minor ocular signs, which may be present in any type of hyperthyroidism, are eyelid retraction ("stare") and lid-lag. These "fear-like" eye-signs result from thyroid hormone's exacerbation of the action of norepinephrine. In hyperthyroid stare (Dalrymple sign) the eyelids are retracted upward more than normal (the normal position is at the superior corneoscleral limbus, where the "white" of the eye begins at the upper border of the iris). In lid-lag (von Graefe's sign), when the patient 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, or treatment by certain anti-adrenergic drugs.

Neither of these ocular signs should be confused with exophthalmos (protrusion of the eyeball) which occurs in one thyroid-related disease (Graves' disease), but which is not caused by the hyperthyroid state in that disease, and is unrelated to it. Exophthalmos when present may exacerbate these signs, however.

Diagnosis
A diagnosis is suspected through blood tests, by measuring the level of thyroid-stimulating hormone (TSH) in the blood. A low TSH (the job of TSH taken over by thyroid-stimulating immunoglobulin [TSI] that act like TSH) indicates increased levels of T4 and/or T3 in the blood. Measuring specific antibodies, such as anti-TSH-receptor antibodies in Graves' disease, may contribute to the diagnosis. In all patients with hyperthyroxinemia, scintigraphy is required in order to distinguish true hyperthyroidism from thyroiditis.

Treatment
The major and generally accepted modalities for treatment of hyperthyroidism in humans involve initial temporary use of suppressive thyrostatics medication, and possibly later use of permanent surgical or radioisotope therapy. All approaches may cause under active thyroid function (hypothyroidism) which is easily managed with levothyroxine supplementation.

Thyrostatics
Thyrostatics are drugs that inhibit the production of thyroid hormones, such as carbimazole (used in UK) and methimazole (used in US), or where these not tolerated then propylthiouracil. Thyrostatics are believed to work by inhibiting the iodination of thyroglobulin by thyroperoxidase.

If too high a dose is used in pharmacological treatment, patients can develop symptoms of hypothyroidism.

Beta-blockers
Beta-blockers do not treat, but rather mask, common symptoms of hyperthyroidism such as palpitations, trembling, and anxiety. Propranolol in the UK, and Metoprolol in the US, are most frequently used to augment treatment for hyperthyroid patients.

Permanent treatments
Surgery as an option predates the use of the less invasive radioisotope therapy, but is still required in cases where the thyroid gland is enlarged and causing compression to the neck structures, or the underlying cause of the hyperthyroidism may be cancerous in origin.

Surgery
Surgery (to 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. However, some Graves' disease patients who cannot tolerate medicines for one reason or another, patients who are allergic to iodine, or patients who refuse radioiodine opt for surgical intervention. Also, some surgeons believe that radioiodine treatment is unsafe in patients with unusually large gland, or those whose eyes have begun to bulge from their sockets, claiming that the massive dose of iodine needed will only exacerbate the patient's symptoms. The procedure is quite safe - some surgeons even perform partial thyroidectomies on an out-patient basis.

Radioiodine
In Iodine-131 (Radioiodine) Radioisotope Therapy, radioactive iodine is given orally (either by pill or liquid) on a one-time basis to destroy the function of a hyperactive gland. The iodine given for ablative treatment is different from the iodine used in a scan. Radioactive iodine is given after a routine iodine scan, and uptake of the iodine is determined to confirm hyperthyroidism. The radioactive iodine is picked up by the active cells in the thyroid and destroys them. Since iodine is only picked up by thyroid cells (and picked up more readily by over-active thyroid cells), the destruction is local, and there are no widespread side effects with this therapy. Radioactive iodine ablation has been safely used for over 50 years, and the only major reasons for not using it are pregnancy and breast-feeding.

Often, due to the difficulty of picking the correct dose, the treatment results in an opposite condition - hypothyroidism. This is considered uncommon since the radioiodine has more affinity towards over-active thyroid cells than it does for the normal ones.

Cats
In veterinary medicine, hyperthyroidism is one of the most common endocrine conditions affecting older domesticated cats. The disease has become significantly more common since the first reports of feline hyperthyroidism in the 1970s. In cats, the cause of hyperthyroidism tends to be benign tumors, but the reason those cats develop such tumors continues to be researched. Most recently, mutations of the thyroid stimulating hormone receptor have been discovered which cause a constitutive activation of the thyroid gland cells. Many other factors may play a role in the pathogenesis of the disease such as goitrogens (isoflavones such as genistein, daidzein and quercertin) and iodine and selenium content in the diet.

The most common presenting symptoms are: rapid weight loss, tachycardia (rapid heart rate), vomiting, diarrhoea, increased consumption of fluids (polydipsia) and food, and increased urine production (polyuria). Other symptoms include hyperactivity, possible aggression, heart murmurs, a gallop rhythm, an unkempt appearance, and large, thick nails. About 70% of afflicted cats also have enlarged thyroid glands (goiter).

The same three treatments used with humans are also options in treating feline hyperthyroidism (surgery, radioiodine treatment, and anti-thyroid drugs). Drugs must be given to cats for the remainder of their lives, but may be the least expensive option, especially for very old cats. Radioiodine treatment and surgery often cure hyperthyroidism. Some veterinarians prefer radioiodine treatment over surgery because it does not carry the risks associated with anesthesia. Radioiodine treatment, however, is not available in all areas for cats. The reason is that this treatment requires nuclear radiological expertise and facilities, since the animal's urine is radioactive for several days after the treatment, requiring special inpatient handling and facilities usually for a total of 3 weeks (first week in total isolation and the next two weeks in close conefinement). Surgery tends to be done only when just one of the thyroid glands is affected (unilateral disease); however following surgery, the remaining gland may become over-active. As in people, one of the most common complications of the surgery is hypothyroidism.

Dogs
Hyperthyroidism is very rare in dogs (occurring in less than 1 or 2% of dogs), who instead tend to have the opposite problem: hypothyroidism. When hyperthyroidism does appear in dogs, it tends to be due to over-supplementation of the thyroid hormone during treatment for hypothryoidism. Symptoms usually disappear when the dose is adjusted.

Occansionally dogs will have functional carinoma in the thryoid; more often (about 90% of the time) this is a very aggressive tumor that is invasive and easily metastasizes or spreads to other tissues (esp. the lungs), making prognosis very poor. While surgery is possible, it is often very difficult due to the invasiveness of the mass in surrounding tissue including the arteries, theesophagus, and windpipe. It may only be possible to reduce the size of the mass, thus relieving symptoms and also allowing time for other treatments to work.

If a dog does have a benign functional carinoma (appears in 10% of the cases), treatment and prognosis is no different from that of the cat. The only real difference is that dogs tend to appear to be asymptomic, with the exception of having an enlarged thyroid gland appearing as a lump on the neck.