Hyperthyroidism

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
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). Thyrotoxicosis (symptoms caused by hyperthyroxinemia) can occur in both hyperthyroidism and thyroiditis. When it causes acutely increased metabolism, it is sometimes called "thyroid storm".

Signs and symptoms
Major clinical features in humans are weight loss (often accompanied by a ravenous appetite), fatigue, weakness, hyperactivity, irritability, apathy, depression, polyuria, and sweating. Additionally, patients may present with a variety of symptoms such as palpitations and arrhythmias (notably atrial fibrillation), 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 recognised. 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 relation between two entities is 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 occular signs should be confused with exopthalmos (protrusion of the eyeball) which occurs in one thyroid-related disease (Grave's disease), but which is not caused by the hyperthyroid state in that disease, and is unrelated to it. Exopthalmos when present may exacerbate these signs, however. .

Diagnosis
A diagnosis is suspected through blood tests, by measuring the level of TSH (thyroid stimulating hormone) in the blood. If TSH is low, there is likely to be increased production of T4 and/or T3. 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 are:

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 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 are even treating partial thyroidectomy on an out-patient basis.

Radioiodine
In Radioiodine (treatment) 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, 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. However, that is usually easily treated by the administration of levothyroxine, which is a pure synthetic form of T4.

Thyrostatics
Thyrostatics are drugs that inhibit the production of thyroid hormones, such as methimazole (Tapazole®) or PTU (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. Hypothyroidism is also a very common result of surgery or radiation treatment as it is difficult to gauge how much of the thyroid gland should be removed. Supplementation with levothyroxine may be required in these cases.

Veterinary medicine
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, it is almost always caused by a benign thyroid adenoma.

The most common presenting symptoms are: rapid weight loss, rapid heart rate, vomiting, diarrhoea, increased water consumption and increased urine production.

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.