Technically, thyrotoxicosis refers to the presence of too much thyroid hormone in the body and hyperthyroidism is when thyrotoxicosis is due to overproduction of thyroid hormone by the thyroid gland.
Grave’s disease is by far the most common cause of hyperthyroidism in Canada. Graves’ disease is named after the Irish physician (Robert Graves). It is sometimes referred to as Basedow’s disease for the German physician (Karl von Basedow) who also described cases.
Graves’ disease affects about one in every 100 people. The disease has a genetic component, although not every member of afflicted families will suffer this condition. It is more common in women than in men, and in smokers compared to non-smokers.
Thyroid Stimulating Immunoglobulin/Thyroid Stimulating Hormone (TSH) Receptor Antibodies
Graves’ disease is an autoimmune disorder. It is caused by an abnormal protein referred to as thyroid stimulating immunoglobulins or TSH receptor antibodies. These antibodies stimulate the thyroid gland to produce large amounts of thyroid hormone (T4 and T3) in an uncontrolled manner. Antibodies are part of the immune system, generally important for fighting infections. In autoimmune conditions, like Graves’ disease, a susceptible person’s immune system gets triggered to produce antibodies that bind to one’s own tissues and potentially cause health problems. The trigger for TSH receptor antibody production in Graves’ is often not clear.
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, palpitations, increased bowel movements 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) can 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. Smokers with Graves’ disease have a higher risk of eye disease; this risk can be reduced by quitting smoking. Some patients with hyperthyroidism, but without Graves’ eye disease, may have the appearance of slightly bulging eyes because of spasm of the muscle of the lids, resulting in a staring appearance.
Thyroid hormones have a wide variety of effects on the body and the symptoms and signs of hyperthyroidism and thyrotoxicosis reflect these. In simple terms, all the metabolic processes “speed up”. For example, the pulse rate can be rapid and occasionally irregular (atrial fibrillation), bowel function may be increased, and the sweat glands may work excessively. The patient may become more irritable or anxious. Despite increased appetite, the patient may lose weight because food intake cannot keep up with the increased metabolism. Some patients can gain weight if the increased appetite is more profound than the increased metabolism.
Thyrotoxicosis is suspected based on the symptoms and signs described above, and confirmed by measurement of the level of Thyroid Stimulating Hormone (TSH) in the blood. If the TSH is suppressed, it indicates that there is too much thyroid hormone and the blood levels of thyroid hormones (Free T4 and T3) are measured to confirm the diagnosis. Occasionally, the clinical presentation is suggestive enough of Graves’ that further testing is unnecessary. If there is doubt as to the cause of thyrotoxicosis, then radioactive iodine scan, TSH receptor antibody measurement, or thyroid ultrasound can help to distinguish Graves’ from other conditions and may be ordered depending on the specific situation.
There is at present no specific treatment for the underlying abnormality (TSH receptor antibodies) that causes hyperthyroidism in Graves’ disease. Since the end result of this problem is an overstimulation of thyroid function, treatment requires blocking thyroid hormone production with antithyroid drugs, destroying the thyroid cells with radioactive iodine or surgically removing the thyroid gland (thyroidectomy).
Some patients will be prescribed a beta blocker medication until the thyroid hormone levels can be normalized. Beta blockers can help with some symptoms of thyrotoxicosis, especially rapid heart rate and tremor, but they do not lower the thyroid hormone levels.
Antithyroid drugs (Propylthiouracil (PTU) and Methimazole are the only ones available in Canada) are often the first treatment given for Graves’ disease. These drugs partially block the production of thyroid hormone by the thyroid, therefore lowering the thyroid hormone levels, but the levels will not return to normal immediately; it often takes weeks. These medications can be used as the initial treatment for patients with Graves’ disease as there is about a 50% chance of hyperthyroidism going into remission. Antithyroid drugs can also be used initially to lower thyroid hormone levels while planning to pursue radioactive iodine ablation or surgery (see below). Often if a patient does not go into remission after 1-2 years of treatment with antithyroid drugs, or if after stopping antithyroid drugs hyperthyroidism recurs, then radioactive iodine ablation or surgery may be recommended for definitive treatment.
A small percentage of patients suffer side effects that very rarely can be severe (liver problems, low white blood cell count). Because of the recent evidence of a higher risk of side effects of Propylthiouracil on liver function, especially in children, the Food and Drug Administration (FDA) in the United States has issued a warning for its use. These drugs sometimes must be used to control hyperthyroidism in pregnancy, however there are rare potential risks to mothers and fetuses with both drugs and the decision about which drug to use in each trimester of pregnancy is controversial. It is preferable to treat hyperthyroidism before considering pregnancy.
Radioactive iodine is a safe and effective treatment for Graves’ hyperthyroidism. However, it occasionally aggravates the eyesight in patients with Graves’ eye disease, especially if they are also smokers. Preventive treatment with corticosteroids is sometimes warranted. In patients with severe active eye disease, radioactive iodine may be avoided or delayed until the eye disease improves.
Radioactive iodine is usually given in the form of a capsule or clear liquid. Because radioactive iodine takes several weeks to months to take its full effect, antithyroid tablets are sometimes given until such time as the full effect occurs.
Occasionally (10-20% of patients), hyperthyroidism persists or recurs after radioactive iodine treatment, but if so, a second dose almost always resolves the hyperthyroidism. Most patients will develop an underactive thyroid (hypothyroidism) after radioactive iodine treatment and require lifelong thyroid hormone replacement therapy. It is important that thyroid blood tests be monitored in patients following radioactive iodine to assess the effectiveness of the treatment and monitor for either hyperthyroidism or hypothyroidism.
Thyroidectomy (thyroid surgery) Surgery may be recommended for patients in whom the goitre is so big that it causes significant discomfort or 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). Thyroidectomy is the treatment of choice if a patient has a known or suspected thyroid cancer in addition to Graves’ disease. Thyroidectomy may be considered in patients with significant Graves’ eye disease who desire definitive treatment. Thyroidectomy is an acceptable treatment for Graves’ disease, but not used as commonly as antithyroid drugs or radioactive iodine due to its invasiveness. Thyroidectomy requires admission to hospital for about 2 days and removal of the gland (by an experienced surgeon). After the thyroid gland is removed, patients need to take thyroid hormone replacement for the rest of their lives to avoid hypothyroidism.
Other Causes of Hyperthyroidism
In Canada, Graves’ disease accounts for at least 90% of all patients with hyperthyroidism. Hyperthyroidism can also occur in patients with nodular goiters or due to a benign thyroid nodule that produces excess thyroid hormone.
Thyrotoxicosis can also be caused by thyroiditis (thyroid inflammation) where the thyroid is damaged and thyroid hormone leaks out into the circulation, temporarily increasing the thyroid hormone levels until this excess thyroid hormone is metabolized or excreted. The most common thyroiditis (subacute thyroiditis) is caused by a viral infection and is painful. Silent thyroiditis is a similar condition but without the painful swelling of the thyroid (please refer to Health Guide 6: Thyroiditis). Silent thyroiditis is due to destructive antibodies and 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.
Reviewed by Dr. Deric Morrison, MD FRCPC, ECNU, Endocrinologist, Assistant Professor, Division of Endocrinology, Department of Medicine, University of Western Ontario, London ON, February 2016, from the original text written by: Irving B. Rosen, MD., FRCS(C), FACS, Professor of Surgery, University of Toronto, Department of Surgery, Mount Sinai Hospital; Consultant in Surgery, Princess Margaret Hospital, Ontario Cancer Institute and Paul G. Walfish CM, MD, FRCP(C), FACP, FRSM., Professor of Medicine, Pediatrics and Otolaryngology, University of Toronto; Senior Consultant, Endocrinology and Metabolism and Head and Neck Oncology Program, Mount Sinai Hospital.