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 both described several cases in the 1830s. Graves’ disease is by far the most common cause of hyperthyroidism in Canada, affecting perhaps one in every 100 people. It appears to be 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. 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 “sped up”. For example, the pulse rate may be 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. Other symptoms include weight loss, shakiness, muscle weakness, and thyroid enlargement (goitre).

Clinically evident eye signs (ophthalmopathy) may 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. The eyes may 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.

To differentiate Graves’ disease from other causes of hyperthyroidism, measurement of TSH receptor antibodies in the blood and/or an imaging test called the radioactive iodine uptake and scan is conducted.

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 a 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 moderate to severe or sight-threatening eye disease; in mild Graves’ eye disease, radioactive iodine can sometimes be administered with steroids 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 also avoided in patients who are pregnant, breastfeeding, or actively trying to conceive.

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 also a common 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 after 12-18 months of treatment and therefore a trial of antithyroid drugs is a reasonable first line therapy.  If hyperthyroidism persists or 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 than methimazole). Because of evidence of side effects of Propylthiouracil on liver function, the FDA has issued a warning for its use.
2. Once antithyroid drugs are stopped, the disease may flare up again and 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.

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 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 patients with thyroid nodules that are secreting thyroid hormones. .

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. Another cause is “silent” thyroiditis, a similar condition but without the painful swelling of the thyroid (please refer to health guide 6). Silent thyroiditis may occur in the post-partum period (a couple of months after delivery). Medications such as amiodarone and immune checkpoint inhibitor cancer medications may also cause hyperthyroidism. A few other rare causes of hyperthyroidism need not be discussed here.

Updated in May 2024 by Anna Lui MD, Endocrinology, 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.