Hyperthyroidism (Thyrotoxicosis)

Graves’ Disease

Graves’ disease is named after the Irish physician (Robert Graves) and in some areas of the world referred to as Basedow’s disease after the German physician (Karl von Basedow).  They bothdescribed several cases in the 1830s  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.

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.

Often a radioactive iodine uptake and scan is ordered in hyperthyroid patients to differentiate Graves’ disease from thyroiditis or hyperfunctioning thyroid nodule(s).  Occasionally, the clinical picture is clear enough that further testing is not necessary.  Sometimes measurement of TSH receptor antibodies is used in addition to or instead of radioactive iodine testing, and when the thyroid feels abnormally large or nodular on physical exam then a thyroid ultrasound may be helpful.

Treatment

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

Radioactive iodine is the most common treatment for hyperthyroidism in North America.  It is usually effective with one treatment though occasionally a second treatment is required.  Most often radioactive iodine treatment results in hypothyroidism requiring thyroid hormone replacement. Radioactive iodine can sometimes worsen Graves’ eye disease and usually is avoided if there is severe eye disease, in mild-moderate Graves’ eye disease Radioactive iodine can sometimes be administered, but with prednisone steroid treatment given with the treatment to reduce the risk of Graves’ eye disease worsening.  Of note smoking dramatically increases the risk of developing Graves’ eye disease, and the risk of it worsening with radioactive iodine treatment.

Radioactive iodine is usually given in the form of a capsule or clear liquid. 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.

Antithyroid Drugs

Antithyroid drugs (of which Propylthiouracil and Methimazole are the only ones available in Canada) are  an acceptable treatment for Graves’ hyperthyroidism. They are often used initially to control thyroid levels. About 20-30% of patients with Graves’ hyperthyroidism may go into remission and therefore a trial of antithyroid drugs is a reasonable first line therapy.  If hyperthyroidism persists of recurs then consideration of radioactive iodine or surgery is recommended to treat the hyperthyroidism.  There are two main drawbacks with antithyroid drugs:

1. Though serious side effects are rare there is a risk of low white blood cells and serious infections, and liver damage (more so with propylthiouracil then methimazole). Because of the recent evidence of side effects of Propylthiouracil on liver function, especially in children, the FDA has issued a warning for its use.
2. Once antithyroid drugs arestopped, there is only about a 30% chance that the disease will not flare up again. Thus most patients require additional treatments.

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  another acceptable treatment for hyperthyroidism. Thyroidectomy is recommended for patients with a  goiter that 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). Also, surgery may be preferred in cases where there are thyroid nodules that are suspicious or indeterminate for thyroid cancer.  Thyroidectomy usually requires admission to hospital for about 1-2 days and removal (by an experienced surgeon) of the gland. 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.

Updated in February 2016 by Dr. Deric Morrison, MD FRCPC, ECNU, Endocrinologist, Assistant Professor, Division of Endocrinology, Department of Medicine, University of Western Ontario, London ON, from the original text written by: Irving B. Rosen, MD., FRCS(C), FACS and Paul G. Walfish CM, MD, FRCP(C), FACP, FRSM.