Causes:

Many permanent or temporary conditions can reduce thyroid hormone secretion and cause hypothyroidism. About 95% of hypothyroidism cases occur from problems that start in the thyroid gland. In such cases, the disorder is called primary hypothyroidism. (Secondary hypothyroidism is caused by disorders of the pituitary gland. Tertiary hypothyroidism is caused by disorders of the hypothalamus.)

The two most common causes of primary hypothyroidism are:

• Hashimoto's thyroiditis. This is an autoimmune condition in which the body's immune system attacks its own cells.
• Overtreatment of hyperthyroidism (an overactive thyroid).

Autoimmune Diseases of the Thyroid

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 T and B cells:

• 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 classifying 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.

Hashimoto's Thyroiditis. The most common form of hypothyroidism in the U.S. is Hashimoto's thyroiditis, a genetic disease named after the Japanese doctor who first described thyroid inflammation. It occurs in about 0.3 - 5 people per 1,000 per year, and women are 15 - 20 times more likely than men to develop this disease.

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. Hashimoto's thyroiditis is permanent and requires lifelong treatment. Both genetic and environmental factors appear to play a role in its development.

One theory proposes that Hashimoto's 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 researchers 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.

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

Riedel's Thyroiditis. Riedel's 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 the scar tissue replaces healthy tissue. Surgery is usually required, although early stages may be treated with corticosteroids or other immunosuppressive drugs.

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 a return to normal thyroid levels. Patients may have symptoms of both hyperthyroidism and hypothyroidism (such as rapid heartbeat, nervousness, and weight loss), and they can feel extremely sick. Symptoms last about 6 - 8 weeks and then resolve in most patients, although each form carries some risk for becoming chronic. Subacute thyroiditis appears to be responsible for about 10% of all cases of hypothyroidism.

The three forms of subacute thyroiditis follow 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 4 - 12 months after delivery. In most cases, a woman develops a small, painless goiter. It is generally self-limiting and requires no therapy unless the hypothyroid phase is prolonged. If so, therapy may be thyroxine replacement for a few months. A doctor will prescribe beta-blockers if the hyperthyroid phase needs treatment. Some evidence suggests that half of women with this condition develop permanent hypothyroidism within 7 years. Women who have had recurrent episodes after previous pregnancies and women who have other autoimmune disorders are at higher risk for this form of subacute thyroiditis.

Painless Sporadic, or Silent, Thyroiditis. This painless condition is very similar to postpartum thyroiditis except it can occur in both men and women and at any age. About 20% of patients with silent thyroiditis may develop chronic hypothyroidism. Treatment considerations are the same as for 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. It recurs in about 2% of patients. Hypothyroidism persists in about 5%. Treatments typically include pain relievers and, in severe cases, corticosteroids.

Post-Treatment of Hyperthyroidism

Up to half or more of patients who receive radioactive iodine 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 5 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, 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 triggers the process leading to Hashimoto's thyroiditis.

Thyroid Surgery

Patients who have complete removal (total thyroidectomy) of the thyroid to treat thyroid cancer need lifetime treatment with 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 grow so that it can produce sufficient amounts of thyroid hormone for normal function. Many doctors recommend thyroid hormone treatment, however, to prevent the formation of additional nodules.

Patients with Graves' disease who have 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 6- or 12-month intervals.

Thyroid Dysfunction Syndromes

Researchers have identified several 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 and Medical Treatments 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 - 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 U.S. and other countries where dietary iodine is abundant. Hyperthyroidism is a less common effect in these regions.

Other Drugs. Drugs used for treating epilepsy, such as phenytoin and carbamazepine, can reduce thyroid levels. Certain antidepressants may cause hypothyroidism, although this is rare. Interferons and interleukins are used for treating hepatitis, multiple sclerosis, and other conditions. Evidence suggests that these drugs increase antibodies that put patients at risk for hypo- or hyperthyroidism. Some drugs used in cancer chemotherapy, such as sunitinib (Sunent) or imatinib (Gleevec), can also cause or worsen hypothyroidism.

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

Other Medical Conditions

A number of medical conditions can involve the thyroid and change the normal gland tissue so that it no longer produces enough thyroid hormone. Examples include hemochromatosis, scleroderma, and amyloidosis.

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 - 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 missing, underdeveloped, or not properly located. In most cases the cause or causes of these conditions are unknown. In about 10 - 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:

• Women who have an underactive (“low”) thyroid, including those who develop the problem during pregnancy, are at increased risk for delivering babies with congenital (newborn) hypothyroidism. Maternal hypothyroidism can also cause premature delivery and low-birth weight.
• Some of the drugs used to treat hyperthyroidism (overactive thyroid) block the production of thyroid hormone. These same drugs can also cross the placenta and cause hypothyroidism in the infant.
• If a pregnant woman has untreated hyperthyroidism, her newborn infant may be hypothyroid for a short period of time. This is because the excess thyroid hormone in the women's blood crosses the placenta and signals the fetus not to produce as much of its own thyroid hormone.
• 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.)
• Premature birth. Temporary hypothyroidism in infants can occur in premature babies.
• The central nervous system connections between the hypothalamus and pituitary gland may mature late; this condition generally resolves 4 - 16 weeks after birth.

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