Hypothyroidism

Description

Alternative Names

Causes

Many permanent or temporary conditions can reduce thyroid hormone secretion and cause hypothyroidism. About 95% of hypothyroidism cases occur from problems that originate in the thyroid gland. In such cases, the disorder is called primary hypothyroidism. In some cases, it is caused by disorders of the pituitary gland (in which case it is known as secondary hypothyroidism) or hypothalamus (tertiary hypothyroidism).

The two most common known causes of primary hypothyroidism are the following:

• Hashimotos thyroiditis. This is an autoimmune condition, in which the bodys immune system attacks its own cells.
• Overtreatment of hyperthyroidism (an overactive thyroid).

Thyroid Autoimmunity (Hashimoto's Thyroiditis and Others)

Hashimoto's thyroiditis, atrophic thyroiditis, and postpartum thyroiditis are all autoimmune diseases of the thyroid. An autoimmune disease occurs when the immune system mistakenly attacks the body's own healthy cells. In the case of autoimmune thyroiditis, a common form of primary hypothyroid disease, the cells under attack are in the thyroid gland.

All forms of thyroid autoimmunity typically start with the following:

• Important immune factors called T- and B-cells infiltrate the thyroid gland in equal numbers. These white blood cells are the primary infection-fighting immune cells. T-cells identify invasive molecules, such as viral proteins, and help B cells to produce antibodies that are designed specifically to attack these invaders.
• In cases of autoimmunity, T-cells are tricked into identifying molecules on the body's own cells as invaders. In such cases, B-cells then produce antibodies, called autoantibodies, which attack those cells.
• In most cases of thyroid autoimmunity, the autoantibodies launch an attack on a thyroid protein called thyroid peroxidase; this attack appears to destroy thyroid cells.

Experts do not know, however why the immune system starts the process that injures the thyroid. Some theories are the following:

• One theory starts with a virus that has a protein resembling a thyroid protein. During an infection, T-cells induce B-cells to secrete specific antibodies that attack the invasive viral protein. Unfortunately, the T-cells are also tricked into inducing a B-cell attack on the similar thyroid protein.
• Genetic factors most likely play some role in autoimmune thyroiditis. For example, many patients with Hashimoto's thyroiditis express a gene called the Fas gene, which interacts with thyroid cells and trigger a process called apoptosis, in which the cells begin to self-destruct. The Fas gene is linked to genes that regulate tumor necrosis factors, which are products of the immune system that trigger a damaging inflammatory response in cells.
• In some women, thyroid autoimmunity may have developed while they were pregnant. In such cases, some evidence suggests that fetal cells accumulated in the mother's thyroid gland, triggering an immune attack.
• In some cases of Hashimoto's thyroiditis, antibodies block a receptor on thyroid cells that binds to thyrotropin (TSH). This effect is more likely to be involved in worsening the disorder, but does not explain initial destruction.
• Some evidence suggests that excess iodine intake triggers the process leading to Hashimoto's thyroiditis.

Hashimotos Thyroiditis. The most common form of hypothyroidism in the US is Hashimotos thyroiditis, a genetic disease named after the Japanese physician who first described thyroid inflammation in 1912. It occurs in approximately 0.3 to five people per 1,000 per year, and women are 15 to 20 times more likely than men to develop this disease.

Click the icon to see an image of Hashimoto's thyroiditis.

An enlargement of the thyroid gland called a goiter is almost always present and may appear as a cyst-like or fibrous growth in the neck. Hashimotos thyroiditis is permanent and requires lifelong treatment. Both genetic and environmental factors appear to play a role in its development.

One interesting theory holds that Hashimotos thyroiditis and Graves disease (a form of hyperthyroidism) are caused by a similar immunologic dysfunction. Similar immune system substances called antibodies are present in both diseases, and some experts believe that the predominance of one or another antibody determines which of the diseases become manifest. The two diseases, then, are essentially two sides of a single coin.

Click the icon to see an image of Grave's disease.

Atrophic Thyroiditis. Atrophic thyroiditis is similar to Hashimoto's thyroiditis, except a goiter is not present.

Riedel's Thyroiditis. Riedels thyroiditis is a rare autoimmune disorder, in which scar tissue progresses in the thyroid until it produces a hard stony mass that suggests cancer. Hypothyroidism develops as healthy tissue is gradually replaced. Surgery is usually required, although early stages may be treated with tamoxifen, corticosteroids, or other immunosuppressive agents.

Autoimmune Thyroiditis Due to Pregnancy. Hypothyroidism may also occur in women who develop antibodies to their own thyroid during pregnancy, causing an inflammation of the thyroid after delivery.

Subacute Thyroiditis

Subacute thyroiditis is a temporary condition that passes through three phases: hyperthyroidism, hypothyroidism, and then a return to normal thyroid levels. Patients may exhibit symptoms of both hyperthyroidism and hypothyroidism (e.g., rapid heartbeat, nervousness, weight loss), and they can feel extremely sick. Symptoms last about six to eight weeks and then resolve in the great majority of patients, although each form carries some risk for becoming chronic. Experts estimate that subacute thyroiditis is responsible for 10% of all cases of hypothyroidism.

There are three forms but they all have a similar course:

Painless Postpartum Subacute Thyroiditis. Postpartum thyroiditis is an autoimmune condition that occurs in up to 10% of pregnant women and tends to develop between four and 12 months after delivery. In most cases, a woman develops a small, painless goiter. It should be noted that only about a third of these women go through the classic three phases typical of other forms of subacute thyroiditis. Although 80% of women with this condition have normal thyroid function within a year, some evidence suggests that half of women with this condition develop permanent hypothyroidism within seven years. Women at higher risk are those who have had recurrent episodes after previous pregnancies and women who have other autoimmune disorders. It is generally self-limiting and requires no therapy unless the hypothyroid phase is prolonged. In such case, thyroxine replacement may be given for a few months. If the hyperthyroid phase requires treatment, beta blockers are typically used.

Painless Sporadic, or Silent, Thyroiditis. This is a painless condition and is very similar to postpartum thyroiditis except it can occur in both men and women and at any age. It can recur, but the risk of recurrence has not been determined. About 20% develop chronic hypothyroidism. Treatment considerations are the same as postpartum subacute thyroiditis.

Painful, or Granulomatous, Thyroiditis. This condition comes on suddenly with flu-like symptoms and severe neck pain and swelling. It generally occurs in the summer and is five times more common in women. This condition recurs in about 2% of patients and hypothyroidism persists in about 5%. Treatments typically include pain relievers and, in severe cases, corticosteroids.

Hyperthyroidism Treatments

Up to half or more of patients who receive radioactive iodide treatments for an overactive thyroid develop permanent hypothyroidism within a year of therapy. This is the standard treatment for Graves disease, which is the most common form of hyperthyroidism, a condition caused by excessive secretion of thyroid hormones.

By the end of five years, about 65% of treated patients have developed hypothyroidism, after which the rate of this condition levels off to about 1% a year. Such patients need to take thyroid hormones for the rest of their lives. Other forms of treatment for overactive thyroid glands using either antithyroid drugs or surgery may also result in hypothyroidism.

Iodide Abnormalities

Too much or too little iodide can cause hypothyroidism. If there is a deficiency of iodide, then the body cannot manufacture thyroxine. About 200 million people around the world have hypothyroidism because of insufficient iodine in their diets. Too much iodide is a signal to inhibit the conversion process of thyroxine to T3. The end result in both cases is inadequate production of thyroid hormones. Some evidence suggests that excess iodine in fact triggers the process leading to Hashimoto's thyroiditis.

Thyroid Surgery

Complete removal (total thyroidectomy) of the thyroid to treat thyroid cancer requires a lifetime of treatment with an appropriate dosage of thyroid hormone. Removing one of the two lobes of the thyroid gland (hemithyroidectomy), usually because of benign growths on the thyroid gland, rarely produces hypothyroidism. The remaining thyroid lobe will generally enlarge so that it can produce sufficient amounts of thyroid hormone for normal function. Many physicians recommend thyroid hormone treatment, however, to prevent the formation of additional nodules.

Click the icon to see an illustrated series detailing thyroid removal.

A small percentage of Graves disease patients who require surgery to remove most of both thyroid lobes (subtotal thyroidectomy) may develop hypothyroidism. It is important to find an experienced surgeon for this procedure and to have the thyroid checked at six- or 12-month intervals.

Thyroid Dysfunction Syndromes

Researchers have identified a number of additional syndromes that also cause hypothyroidism. These generally involve abnormalities in thyroid hormone itself or genetic deficiencies in certain proteins that impair thyroid hormone conversion processes or responses.

Drugs that Reduce Thyroid Levels

Lithium. Lithium, a drug widely used to treat psychiatric disorders, has multiple effects on thyroid hormone synthesis and secretion. Up to 50% of patients who take lithium develop a goiter, with 20% developing symptomatic hypothyroidism, and another 20% to 30% developing hypothyroidism without symptoms.

Amiodarone. The drug amiodarone (Cordarone), which is used to treat abnormal heart rhythms, contains high levels of iodine and can induce hyper- or hypothyroidism, particularly in patients with existing thyroid problems. Hypothyroidism occurs in 20% of patients and is the more common effect in the US and other countries where dietary iodine is abundant. Hyperthyroidism is a less common effect in these regions.

Other Drugs. Drugs used for epilepsy, including phenytoin and carbamazepine, reduce thyroid levels. Certain antidepressants may cause hypothyroidism, although this effect is infrequent. Interferons and interleukins are used in hepatitis, multiple sclerosis, and other conditions. Evidence suggests that these drugs increase antibodies that put patients at risk for hypo- or hyperthyroidism. Many other medications contain iodine or have properties that affect the thyroid, although their effects are almost always reversible when they are stopped. Large doses of selenium, a common over-the-counter supplement, may lower thyroid levels. Some drugs used in cancer chemotherapy can also cause hypothyroidism.

Radiation

High-dose radiation for cancers of the head or neck and for Hodgkin's disease causes hypothyroidism in up to 65% of patients within 10 years after treatment.

Causes of Secondary and Tertiary Hypothyroidism

In rare instances, usually due to a tumor, the pituitary gland will fail to produce thyrotropin (TSH), the hormone that stimulates the thyroid to produce its hormones. In such cases, the thyroid gland withers. When this happens, secondary hypothyroidism occurs.

Causes of Hypothyroidism in Infants

Hypothyroidism in newborns (known as congenital hypothyroidism) occurs in one in every 3,000 to 4,000 births, making it the most common hormonal disorder in infants. In 90% of these cases, it persists throughout life.

Permanent Congenital Hypothyroidism. In up to 85% of permanent congenital hypothyroidism cases, the thyroid gland is either missing, underdeveloped, or not properly located. In most cases the cause or causes of these conditions are unknown. In about 10% to 15% of cases, processes involved in hormone production are impaired, most likely because of genetic abnormalities. In less than 5% of cases, the pituitary or hypothalamus function abnormally.

Temporary Hypothyroidism in Infants. Temporary hypothyroidism can also occur in infants. In about 20% of cases, the cause remains unknown. The known causes stem from various immunologic, environmental, and genetic factors, including those in the mother:

• Thyroid dysfunction in the mother during pregnancy. Hypothyroidism during pregnancy and anti-thyroid medications in pregnant hyperthyroid women are major causes of temporary hypothyroidism in infants. All mothers with hypothyroidism should be treated effectively. Their babies' risk for thyroid dysfunction can persist if therapy is inadequate.
• Iodine deficiency. This may cause temporary hypothyroidism. (Exposure to too much iodine immediately after birth, for example, from iodine-containing disinfectants or medicines, can also cause thyroid dysfunction.)
• Being premature.
• Kidney disease. Temporary hypothyroidism in infants can also occur in premature babies and, rarely, in those with kidney disease.
• The central nervous system connections between the hypothalamus and pituitary gland may also mature late; this condition generally resolves four to 16 weeks after birth.

Children with temporary congenital hypothyroidism should be followed-up regularly during adolescence and adulthood for possible thyroid problems. The risk is highest in these adult women during pregnancy. Newborn siblings of these children should also be screened for possible thyroid defects.