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Friday, November 29, 2013

Hyperthyroidism (Thyrotoxicosis)

Graves-Basedow Disease

Graves-Basedow disease is named after the Irish physician (Robert Graves) and the German physician (Karl von Basedow) who described several cases in 1835 and 1840. It was actually first described by Parry a few years earlier. In Europe the disease is known as Basedow’s disease. In all countries it is also known as "Thyrotoxicosis". Graves’ disease is by far the most common cause of hyperthyroidism in Canada, affecting perhaps one in every 100 people. It appears to becoming even more common. The disease has a genetic component, although not every member of the afflicted families will suffer this condition. It is more common in females than in males.
Thyroid Stimulating Antibody
Graves’ disease is an autoimmune disorder. It is caused by an abnormal protein called the thyroid stimulating antibody. This antibody stimulates the thyroid gland to produce large amounts of thyroid hormone in an uncontrolled manner. In normal people, the production of the thyroid stimulating antibody (and other abnormal antibodies) is prevented by a surveillance system. This system consists of certain blood cells called suppressor and helper lymphocytes, Killer (K) cells and other constituents. Measurement of the thyroid stimulating antibody present in the blood of patients with Graves’ disease is not usually necessary, in order to establish the diagnosis.
Clinical Features
The symptoms and signs of Graves’ hyperthyroidism are due to the effects of excess amounts of thyroid hormone on body function and metabolism. Common symptoms include weight loss, nervousness, irritability, intolerance to hot weather, excessive sweating, shakiness, and muscle weakness. Other signs include a rapid pulse, loss of body fat and muscle bulk, thyroid enlargement (goitre), fine tremors of the fingers and hot, moist, velvety skin.
Clinically evident eye signs (ophthalmopathy) occur in patients with Graves’ disease. Fortunately only approximately 5% are severe. The eyes, which bulge from their sockets can be red and watery and the lids are swollen. Quite often the eyes do not move normally because the swollen eye muscles are unable to work precisely and patients can experience double vision. Some patients with Graves’ hyperthyroidism may have slightly bulging eyes because of spasm of the muscle of the lids, giving them a staring appearance.
Thyroid hormones have a wide variety of effects on the body and the symptoms and signs reflect these. In simple terms, all the metabolic processes are "speeded up". For example, the pulse rate is rapid (over 100) and occasionally irregular (atrial fibrillation), bowel function is increased (diarrhoea), and the sweat glands work excessively. The nervous system is also stimulated so that the patient becomes irritable and nervous. Despite increased appetite, the patient usually loses weight because food intake cannot keep up with the increased breakdown of body proteins. The end result is a thin, hot, nervous patient with "poppy" eyes and goitre - a classical clinical situation quickly recognized by any medical practitioner who has previously seen such a patient.
Because Graves’ hyperthyroidism is caused by a genetically determined abnormality of the immune system, the problem is complex and there is at present no specific treatment for the underlying abnormality. Since the end result of this problem is an over stimulation of thyroid function, treatment of the symptoms requires blocking thyroid hormone production with antithyroid drugs, destroying the thyroid cells with radioactive iodine or surgically removing the thyroid gland (thyroidectomy).
Radioactive Iodine
Although radioactive iodine is by far the simplest and most convenient treatment, its use in younger adults and children has previously been a matter of concern because of the possible harmful effects of radiation. Radioactive iodine has been used for over 40 years and there is no known evidence of any harmful effects. In North America most thyroid specialists would recommend its use in most patients with Graves’ disease over the age of 20-25 because it has a higher chance of long-term success (resolution of hyperthyroidism) than antithyroid drugs. Its use in adolescents is increasing. However, it occasionally aggravates the eye sight and preventive treatment with corticosteroids is sometimes warranted.
Radioactive iodine is usually given in the form of a capsule. The dose is calculated from the size of the goitre and the 24hr iodine uptake obtained by performing a "Thyroid Uptake Test." Because radioactive iodine takes several weeks to take its full effect, antithyroid tablets are sometimes given until such time as the full effect occurs.
After treatment with radioactive iodine, it is hoped that enough of the thyroid gland remains to function normally. Occasionally (10-20% of patients), the gland becomes overactive again since the abnormal stimulating antibody is still being produced by the lymphocytes. In other patients, there is a strong tendency for the remaining thyroid gland to become underactive (hypothyroidism) - perhaps 80% of all patients with Graves’ disease will eventually (1-10 years after the radioiodine treatment) require lifelong thyroid hormone replacement therapy. This is not considered a problem as long as the hypothyroidism is recognized and treated. It is much more of a problem for patients to have a recurrence of hyperthyroidism because of failure to remove enough gland or if too small dose of radioactive iodine is given. Indeed, some specialists deliberately propose to destroy the thyroid in order to prevent a recurrence of the hyperthyroidism, and immediately treat with thyroid hormone in anticipation of hypothyroidism. - Health Guide #07: Hyperthyroidism (Thyrotoxicosis)
Antithyroid Drugs
Antithyroid drugs (of which Propylthiouracil and Methimazole are the only ones available in Canada) are commonly used in children and adults under the age of 20-25. It may also be used at any age so as to bring about remissions, or prior to ablation therapy. There are two main drawbacks with this type of treatment:
  1. Patients must take tablets for many months or years, the recommended period of time for the treatment is 12 to 18 months;
  2. Once treatment is stopped, there is only about a 50% chance that the disease will not flare up again. Thus most patients require additional treatments.
In addition a very small percentage suffer side effects that very rarely can be severe (liver problems, low white blood cell count). Because of recent the evidence of side effects of Propylthiouracil on liver function, especially in children, the FDA has issued a warning for its use. Propylthiouracil is still the treatment of choice during pregnancy since there is unclear evidence about Methimazole side effects in the fetus (aplasia cutis, choanal atresia). It is preferable to treat the hyperthyroidism before considering pregnancy.
Another medication that can be given to treat the symptoms of hyperthyroidism is Propranolol or other beta-blockers. This drug blocks the effects of excess thyroid hormones on the heart, blood vessels, and nervous system, but has no direct effect on the thyroid gland. It is contraindicated in patients with asthma.
Thyroidectomy (thyroid surgery)
Surgery is sometimes recommended for the 80% of patients under the age 20 who have a recurrence of hyperthyroidism after antithyroid drugs. Thyroidectomy is also recommended for patients of any age in whom the goitre is so big that it causes blockage of the windpipe (trachea) or food passage (oesophagus) or in cases where a speedy control of hyperthyroidism is necessary (for example, difficult to manage cardiac arrhythmia). In England and Europe, thyroidectomy is performed for Graves’ disease much more often than in Canada, largely because of experience and tradition. Thyroidectomy requires admission to hospital for about 2 days and removal (by an experienced surgeon) of the gland. Some centres offer the procedure as a day-surgery and/or with video-assisted minimally invasive techniques. After the thyroid gland is removed replacement with thyroxine is a life-long requirement.
Other Causes of Hyperthyroidism
In Canada, Graves’ disease accounts for at least 90% of all patients with hyperthyroidism. Hyperthyroidism can also occur in older patients with long-standing nodular goitres.
Other uncommon causes of hyperthyroidism in Canada are painful (subacute) thyroiditis caused by a viral infection of the thyroid gland in which the hyperthyroidism is due to leakage of thyroid hormones from the swollen, damaged gland. Also known as "silent" thyroiditis, a similar condition but without the painful swelling of the thyroid (please refer to health guide 6). Silent thyroiditis frequently occurs in the post-partum period (a couple of months after delivery). A few other rare causes of hyperthyroidism need not be discussed here.

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