Hyperthyroidism

Overview

Hyperthyroidism is a disease in which the thyroid gland is over active and makes too much thyroid hormone. Like most conditions of the thyroid gland, it is more common in women. Hyperthyroidism can be caused by either overproduction of thyroid hormone or excessive release of thyroid hormone from the thyroid gland due to inflammation and/or destruction of the thyroid cells. It is important to distinguish between these two causes, in order to choose the appropriate treatment. A thyroid uptake scan (also known as a radioactive iodine scan) is a test that can help to distinguish between these two causes. Problems which cause overproduction of thyroid hormone which is derived from iodine will have increased uptake of radioactive iodine on thyroid scanning (i.e. a “hot” scan), while thyroid gland inflammation and/or destruction will have low uptake of iodine on thyroid scan. Overproduction of thyroid hormone is the most common cause of hyperthyroidism and can be caused by Graves’ disease, toxic multi-nodular goiter, and toxic adenoma.

Symptoms of hyperthyroidism

Symptoms that may be associated with hyperthyroidism include anxiety, insomnia (inability to sleep through the night), tremors, palpitations, weight loss, muscle weakness, heat intolerance, excessive sweating, and menstrual changes. The number, degree, and severity of these symptoms can provide some clue as to the severity of hyperthyroidism.

Diagnosis

Diagnosing hyperthyroidism is based on history and physical examination and confirmatory abnormal laboratory testing. On physical exam, the physician may find that the patient has a rapid heart rate (tachycardia), irregular heartbeats (arrhythmias, including atrial fibrillation), eye symptoms (such as dryness, burning, bulging, double vision), or hand tremors. In addition, the thyroid gland may be larger than normal.

Laboratory testing to confirm the diagnosis of hyperthyroidism will include thyroid function tests. Usually, the TSH level will be lower than normal and the T3 and/or T4 levels will be higher than normal. Subclinical hyperthyroidism is defined as cases where there are no clear symptoms or physical signs of hyperthyroidism on history and physical examination, but the blood level of TSH is low, and T3/T4 levels are normal.

Thyroid uptake scanning is used to determine if the thyroid is making too much thyroid hormone, leading to a high, or “hot” uptake scan versus if the thyroid is being destroyed (as in thyroiditis), in which case the scan will be a low, or “cold” uptake scan.

Common causes of hyperthyroidism

Graves’ disease

Graves’ disease is an autoimmune problem where the body’s immune system generates antibodies against the thyrotopin receptor (TR) which stimulates the TSH-R, increasing thyroid hormone production and release. It is the most common cause of hyperthyroidism. Laboratory findings demonstrate a low TSH and high T4 and T3. The thyroid uptake scan will be high, or “hot”. On physical exam, patients with Graves’ disease may have an enlarged thyroid gland, bulging eyes and violet plaque-like lesions, on the front of their lower legs, which are possibly associated with itchiness. Graves’ disease is the most common cause of hyperthyroidism in the United States.

Toxic multinodular goiter

Hyperthyroidism due to toxic multinodular goiter occurs when one or more nodules (growths) in the thyroid make too much thyroid hormone. In general, the hyperthyroidism tends to be less severe than that seen in Graves’ disease. Laboratory diagnosis is the same as in other cases of hyperthyroidism with low TSH and high T4 and T3 levels. Thyroid uptake scans may note several separate “hot” spots corresponding to the hyperactive nodules, while the rest of the gland has decreased activity. Although toxic nodular goiter is less common than Graves’ disease, its prevalence increases with age and in the presence of dietary iodine deficiency. Thus, toxic nodular goiter may be more common than Graves’ in older patients, especially in regions of iodine deficiency.

Toxic adenoma

If a single nodule, or a solitary toxic adenoma, in an otherwise normal thyroid gland makes too much thyroid hormone, it can lead to hyperthyroidism. This is a less common cause of hyperthyroidism than either Graves’ disease or toxic multinodular goiter. The diagnosis can be made in the same fashion as above.

Painless and subacute thyroiditis

Subacute thyroiditis occurs due to inflammation of the thyroid tissue with release of hormone from the thyroid gland. It can be caused by viral infection and is characterized by fever and thyroid pain.  Painless thyroiditis can occur with lithium, cytokine (IFN-a), tyrosine kinase inhibitor therapy, or amiodarone treatment.

Treatment of hyperthyroidism

The three main treatments for hyperthyroidism are: 1) medical therapy, 2) surgery, and 3) RAI ablation. The best treatment depends on a number of factors and the treatment plan should be made by a team of experts in thyroid disease, including endocrinologists and surgeons. Typically, the first treatment that is usually tried once a diagnosis is made is usually anti-thyroid medications. If medical therapy does not work, then a more definitive therapy such as surgery or RAI ablation is considered. The choice between surgery and RAI ablation will depend on the expertise and experience of the patient’s doctors. Both have equal success rates and low risks of complications.

Medical Therapy

The two goals for medical therapy are to control symptoms and to prevent excess thyroid hormone production. Beta-blockers are medications that are used to control symptoms such as palpitations, anxiety, and tremors. These medications are usually given until thyroid function tests have returned to normal. Anti-thyroid medications are used to block excess thyroid hormone production. The two drugs used most commonly are Methimazole and propylthiouracil (PTU). Methimazole is the preferred medication because it acts faster and has fewer side effects. Usually, patients are put on anti-thyroid medications for one to two years. At that point the medication is stopped. If hyperthyroidism returns, as happens in over 50% of patients, a more definitive treatment to cure the disease is considered. The options for definitive treatment of hyperthyroidism are RAI ablation or surgical removal of all or part of the thyroid. Both are effective in the long-term control of hyperthyroidism.

Surgery

Surgery for hyperthyroidism usually means removing the entire thyroid gland (total thyroidectomy) with the goal of making the patient hypothyroid and to start thyroid hormone replacement pills to better control the thyroid hormone levels in the body. If surgery is chosen as the primary therapy, near total or total thyroidectomy is the procedure of choice.  Thyroidectomy has a high cure rate and a nearly  0% risk of recurrence.  In contrast, a subtotal thyroidectomy may have a 8% risk of persistence or recurrence of hyperthyroidism at 5 years. Surgery does have the small risk of postoperative complications, but it has the advantages of rapidly fixing the hyperthyroidism. When performed by an experienced surgeon, thyroid surgery is safe. (See Thyroid Surgery) After a total thyroidectomy, patients must take thyroid hormone replacement pills because removing the whole thyroid will make them hypothyroid. Patients with a large goiter and associated compressive symptoms, any suspicion for thyroid cancer, moderate or severe eye disease due to Graves’ disease, and pregnant patients who cannot tolerate anti-thyroid medications should get an operation to remove their thyroid gland.

Radioactive iodine ablation

When RAI ablation is selected for treatment of hypethyroidism, the patient is given a pill that contains radioactive iodine that is taken up by thyroid cells and destroys them from the inside out. RAI ablation has the advantage of avoiding thyroid surgery. Currently, most patients are given doses of RAI that are high enough to destroy the entire thyroid and then are started on thyroid hormone replacement pills. This controls the hyperthyroidism sooner and more definitively. With proper treatment, hypothyroidism following RAI ablation should occur within three to six months. In general, the chance of the hyperthyroidism returning (i.e. recurrence) is less than 3%. A disadvantage of RAI ablation is the potential to worsen thyroid eye disease (ophthalmopathy) associated with severe cases of Graves’ disease. Patients who are pregnant, have large thyroids, thyroid nodules suspicious for thyroid cancer, risk factors for thyroid cancer, or who have compressive symptoms from a large goiter should not have RAI ablation. There is debate as to whether young children should have RAI ablation because they may then be at increased risk for other cancers and heart damage later on in life. In general, most practitioners do not recommend RAI ablation for patients younger than 15 years old.