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	Introduction
	Causes
	Symptoms
	Diagnosis
	Risk Factors
	Complications
	Treatment
	Resources
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Hypothyroidism

Highlights

Congenital Hypothyroidism and Maternal Hyperthyroidism

Thyroid-lowering medications used for treating Graves disease, the most common cause of hyperthyroidism (overactive thyroid), can cause babies to be born with hypothyroidism (underactive thyroid). Research presented at the 2006 annual meeting of the American Thyroid Association suggests that hyperthyroidism can be effectively managed during pregnancy without causing newborn hypothyroidism. The researchers suggest that:

• Pregnant women with Graves disease should take the lowest possible dose of their thyroid medication
• It is safe for women with Graves disease to maintain thyroid levels in the upper-normal range while pregnant

Low-Normal Thyroid and Metabolic Syndrome

• Thyroid levels in the low-normal range may increase the risk of unhealthy cholesterol levels, high blood sugar, and abdominal obesity -- indicators of metabolic syndrome -- according to a 2006 study in the Journal of Clinical Endocrinology and Metabolism.
• Metabolic syndrome is a cluster of conditions, (including abdominal obesity, high blood sugar, and unhealthy cholesterol levels), which increases the risk for heart disease. However, many experts do not believe that treating subclinical hypothyroidism (mildly underactive thyroid) can help prevent heart problems. More research is underway.

Subclinical Hypothyroidism and Mood

A large study of elderly people, published in the Annals of Internal Medicine, suggests that subclinical hypothyroidism does not cause depression, anxiety, or impaired cognition. The study included nearly 6,000 people age 65 years and older.

Introduction

The thyroid is a small, butterfly-shaped gland located in the front of the neck that produces hormones, notably thyroxine (T4) and triiodothyronine (T3), which stimulate vital processes in every part of the body. These thyroid hormones have a major impact on the following functions:

• Growth
• Use of energy and oxygen
• Heat production
• Fertility
• The use of vitamins, proteins, carbohydrates, fats, electrolytes, and water
• Immune regulation in the intestine

These hormones can also alter the actions of other hormones and drugs.

The thyroid gland, a part of the endocrine (hormone) system, plays a major role in regulating the body's metabolism.

Iodide and Thyroid Hormone Production

Regulating thyroid function is a complex and important process that involves several factors, including iodide and four thyroid hormones. Any abnormality in this intricate system of hormone synthesis and production can have far-reaching consequences on health.

Iodide. An understanding of the multi-step thyroid hormone process begins with iodide, a salt that is extracted from the blood and trapped by the thyroid gland. Iodide is converted to iodine in the thyroid gland. (Eighty percent of the body's iodine supply is stored here.) Iodine is the material used to make the hormone thyroxine (T4).

Thyroid Hormones. Four hormones are critical in the regulation of thyroid function:

• Thyroxine (T4) and Triiodothyronine (T3). Thyroxine (T4) is the key thyroid hormone. Low levels of T4 produce hypothyroidism, and high levels produce hyperthyroidism. Thyroxine converts to triiodothyronine (T3), which is a more biologically active hormone. Only about 20% of triiodothyronine is actually formed in the thyroid gland. The rest is manufactured from circulating thyroxine in tissues outside the thyroid, such as those in the liver and kidney. Once T4 and T3 are in circulation, they typically bind to substances called thyroid hormone transport proteins, after which they become inactive.
• Thyrotropin. Thyrotropin (also called thyroid-stimulating hormone or TSH) is another very important hormone in the process. Secreted by the pituitary gland, this hormone directly influences the process of iodine trapping and thyroid hormone production. When thyroxine levels drop even slightly, the pituitary gland goes into action to pump up secretion of thyrotropin so that it can stimulate thyroxine production. So, when T4 levels fall, TSH levels increase.
• Thyrotropin-releasing hormone (TRH), the final critical thyroid hormone, is produced in a region in the brain called the hypothalamus, which monitors thyrotropin levels.

Click the icon to see an image of the pituitary gland.

Click the icon to see an image of the pituitary gland and TSH.

Hypothyroidism

Hypothyroidism occurs when thyroxine (T4) levels drop so low that body processes begin to slow down. Hypothyroidism was first diagnosed in the late nineteenth century when doctors observed that surgical removal of the thyroid resulted in the swelling of the hands, face, feet, and tissues around the eyes. They named this syndrome myxedema and correctly concluded that it was the outcome of the absence of substances, thyroid hormones, normally produced by the thyroid gland. Hypothyroidism is usually progressive and irreversible. Treatment, however, is nearly always completely successful and allows a patient to live a fully normal life.

Subclinical Hypothyroidism

Subclinical hypothyroidism (mildly underactive thyroid), also called early-stage hypothyroidism, is a condition in which thyrotropin (TSH) levels have started to increase in response to an early decline in T4 levels in the thyroid. However, blood tests for T4 are still normal. The patient may have mild symptoms (usually slight fatigue) or none at all. Mildly underactive thyroid is very common (affecting about 10 million Americans) and is a topic of considerable debate among professionals because it is not clear how to manage this condition.

For instance, mildly underactive thyroid does not progress to the full-blown disorder in most people. Experts estimate that each year approximately 2 - 5% of people with mildly underactive thyroid will go on to develop overt hypothyroidism. Other factors associated with a higher risk include being an older woman (up to 20% of women over age 60 have subclinical hypothyroidism), having a goiter (enlarged thyroid gland) or thyroid antibodies, or harboring immune factors that suggest an autoimmune condition.

Mildly underactive thyroid is determined on the basis of the TSH laboratory blood tests. According to a 2004 consensus statement from the American Thyroid Association, the American Association of Clinical Endocrinologists, and the Endocrine Society, the normal range of TSH concentration falls between 0.45 and 4.5 mU/L. Patients with mildly underactive thyroid have TSH levels between 4.5 mU/L and 10mU/L. Patients with levels greater than 10mU/L are considered to have overt hypothyroidism and should be treated with medication.

For patients in the mildly underactive thyroid range, treatment decisions are less clear. The consensus committee recommended against routine treatment for patients with mildly underactive thyroid , but did suggest repeat screenings of thyroid function every 6 - 12 months to detect any changes in TSH levels. However, these are general guidelines, and individual cases and risk factors may differ. Patients should discuss with their doctor the course of action that is most appropriate for them.

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. (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).

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 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.

Experts do not know why the immune system starts the process that injures the thyroid. Some theories follow:

• 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 triggers 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 bind 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.

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.

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. 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 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. 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 tamoxifen, 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 exhibit symptoms of both hyperthyroidism and hypothyroidism (rapid heartbeat, nervousness, 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. Experts estimate that subacute thyroiditis is responsible for 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. 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 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. It is generally self-limiting and requires no therapy unless the hypothyroid phase is prolonged. In such cases, therapy may be thyroxine replacement for a few months. A doctor will prescribe beta blockers if the hyperthyroid phase requires treatment.

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.

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 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

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 doctors 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 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 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

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 - 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:

• Hypothyroidism. 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.
• Hyperthyroidism. Graves disease is the most common cause of maternal hyperthyroidism (overactive or high thyroid). Some of the drugs used to treat hyperthyroidism can cause hypothyroidism in the infant. Some research indicates that using the lowest possible dose of thyroid-lowering medication can minimize the risk of congenital hypothyroidism. (The research also suggests that it is safe for women with Graves disease to remain in a mildly hyperthyroid state during pregnancy.
• 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 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 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.

Symptoms

Early Symptoms. Early symptoms of hypothyroidism are subtle and, in older people, can be easily mistaken for symptoms of stress or aging. They include:

• Chronic fatigue
• Sensitivityto cold
• Headache
• Muscle and joint aches
• Weight gain, despite diminished appetite
• Constipation
• Dry skin

In premenopausal women, early symptoms can interfere with fertility. They may experience heavy periods or, in rare cases, a milky discharge from the breasts. A history of miscarriage may be a sign of impending hypothyroidism. Studies suggest that even if thyroid levels are normal, women who have a history of miscarriages often have antithyroid antibodies during early pregnancy and are at risk for developing autoimmune thyroiditis over time.

Later Symptoms. As free thyroxine levels fall over the following months, other symptoms may develop:

• Impaired mental activity, including concentration and memory, particularly in the elderly.
• Depression. Some experts believe that even mild thyroid failure may increase susceptibility to major depression.
• Muscle weakness, numbness, pain, and cramps. This can cause an unsteady gait. Muscle cramps are common, and carpal tunnel syndrome or symptoms similar to arthritis sometimes develop. In some cases, the arms and legs may feel numb.
• Numbness in the fingers.
• Hearing loss.
• Husky voice.
• Continuing weight gain and possible obesity, in spite of low appetite.
• Some people experience less sweating, and their skin becomes pale.
• Skin and hair changes. Skin becomes pale, rough, and dry. Patients may sweat less. Hair coarsens and even falls out. Nails become brittle.
• Snoring and obstructive sleep apnea (a condition in which in the soft palate in the throat collapses at intervals during sleep, thereby blocking the passage of air).

Symptoms of Secondary (Pituitary-Related) Hypothyroidism

Secondary hypothyroidism, caused by tumors or other growths on the pituitary, produces the usual symptoms of primary hypothyroidism. In addition, sexual drive and fertility may be impaired in both men and women. Patients may also feel exhausted, crave salt, and have low blood pressure. Headaches and visual disturbances may develop, which are directly related to the pituitary tumor.

Hypothyroidism occurs when the thyroid gland is underactive. The condition may affect all body functions. The rate of metabolism slows, causing mental and physical sluggishness. Myxedema, a medical emergency, is the most severe form of hypothyroidism.A problem with the thyroid itself (primary) or malfunction of the pituitary gland (secondary) or hypothalamus (tertiary) can cause hypothyroidism.

Symptoms in Infants and Children

All babies are now screened for hypothyroidism in order to prevent retardation that can occur if treatment is delayed. Symptoms of hypothyroidism in children vary depending on when the problem first develops.

• Most children who are born with a defect that causes congenital hypothyroidism have no obvious symptoms. Symptoms that do appear in newborns may include jaundice (yellowish skin), noisy breathing, and an enlarged tongue.
• Early symptoms of undetected and untreatedhypothyroidism in infants include feeding problems, failure to thrive, constipation, hoarseness, and sleepiness.
• Later on, symptoms in untreated children include protruding abdomens; rough, dry skin; and delayed teething. Rarely, in advanced cases, yellow raised bumps (called xanthomas) may appear under the skin, the result of cholesterol build-up.
• If they do not receive proper treatment in time, children with hypothyroidism may be extremely short for their age, have a puffy, bloated appearance, and have below-normal intelligence. Any child whose growth is abnormally slow should be examined for hypothyroidism.

Diagnosis

Advances in diagnostic methods now make it possible to detect hypothyroidism in almost all cases before severe symptoms develop. Doctors can diagnosis hypothyroidism after completing a history and physical exam of the patient and performing sensitive laboratory tests on the patient's blood.

Physical Examination

The doctor will check the heart, eyes, hair, skin, and reflexes for signs of hypothyroidism.

Goiter. The presence of a goiter (an enlarged thyroid), especially a rubbery, painless one, may be an indication of Hashimoto's disease. If the thyroid is tender and enlarged but not necessarily symmetrical, the doctor may suspect subacute thyroiditis. A diffusely enlarged gland may occur in hereditary hypothyroidism, in postpartum patients, or from use of iodides or lithium. Goiters may also develop in people with iodide deficiency.

Thyroid Neck Check. Women who are experiencing menopausal symptoms that may be masking those of hypothyroidism should perform a simple self-examination called the Thyroid Neck Check:

• Hold a mirror in front of the area of the neck where the thyroid gland is located. This area is just below the Adam's apple and right above the collarbone. (Note: The Adam's apple is not the thyroid location.)
• Tip the head back.
• Take a drink of water and swallow, watching the neck during the process.
• Check for any bulging or protrusions. If any is detected, call a doctor for a check up.

Thyroid Hormone and Antibody Tests

In diagnosing hypothyroidism, blood tests measuring hormone levels are needed to make a correct diagnosis. In some cases, antibody tests are also helpful.

Thyroxine (T4). Hypothyroidism is a condition marked by low thyroxine (T4) hormone levels, and a test can measure levels of this hormone in the blood. However, this test is usually inadequate for the following reasons:

• T4 levels can be normal early in the disease process leading to hypothyroidism. If hypothyroidism is suspected, other tests are needed.
• T4 levels can be low in patients who do not have hypothyroidism. For instance, thyroxine can be extremely variable in very elderly or seriously ill patients and during pregnancy.

Measuring thyroxine is usually performed using a process called a T3 resin uptake to correct for the presence of medications (such as birth control pills, aspirin, and others) that could distort the results. Other tests are needed to confirm a diagnosis of hypothyroidism.

Thyrotropin (Thyroid-Stimulating Hormone or TSH). Measuring TSH is the most sensitive indicator of hypothyroidism. (As with thyroxine levels, however, TSH levels can vary in pregnant women and patients who are ill with other conditions.) In general, results indicate the following:

• TSH levels over 10mU/L. This is a clear indicator of hypothyroidism if T4 levels are low -- and, in most cases, even if they are normal. Patients usually require thyroxine (T4) replacement therapy. They should also be tested for high cholesterol levels and antithyroid antibodies.
• Levels between 4.5 mU/L - 10 mU/L. Patients with signs and symptoms of hypothyroidism usually need thyroxine replacement therapy. Patients without symptoms have subclinical hypothyroidism and should be rechecked every 6 - 12 months. Antibody tests may also be performed.
• TSH levels between 0.45 mU/L - 4.5 mU/L. These indicate normal thyroid function. (Abnormally low levels suggest hyperthyroidism, which is overactive thyroid.)
• Specific TSH measurement -- even if it is significantly higher than 10 mU/L -- is not associated with the severity of the condition. This can be determined only by measuring thyroxine levels and evaluating the patient's symptoms.

Antithyroid Antibodies. If TSH levels suggest hypothyroidism or subclinical hypothyroidism, the doctor may choose to perform a blood test for specific antithyroid antibodies that act against a factor called thyroperoxidase (TPO). Tests can also check for antibodies to thyroglobulin. Results depend on the patient's condition:

• Patients with confirmed hypothyroidism (TSH levels over 10 mU/L). Positive test results in such patients confirm the need for thyroxine replacement therapy. (Even if antibody results are negative, these patients usually require thyroxine replacement therapy.) About 90% of patients with Hashimoto's thyroiditis test positive for antibodies to thyroperoxidase, and up to half have thyroglobulin antibodies.
• Patients with subclinical hypothyroidism (TSH between 4.5 mU/L - 10 mU/L). If antibody levels are high, thyroxine therapy is usually warranted, since it indicates an underlying autoimmunity condition that poses a high risk for later thyroid failure. If the tests are negative, but patients have thyroid-related problems (such as high cholesterol, female infertility), they should be monitored annually with hormone tests.

About 10% of the American population and 25% of women over 60 years old carry these antibodies, and the majority of these women have no thyroid problems. Only about 0.5% have full-blown hypothyroidism, and 10% have subclinical hypothyroidism. In one 10-year study, however, people with normal thyroid results and high levels of antibodies still had an annual risk of 2 - 4% for developing hypothyroidism.

Other Hormone Tests Used for Thyroid Function. Other hormone tests are done if hyperthyroidism is suspected. They include tests for triiodothyronine (T3) and thyroglobulin (also called thyroid binding globulin). Such measurements, however, may also be helpful in detecting sudden temporary increases in thyroid hormone (thyrotoxicosis) that can precede certain forms of autoimmune thyroiditis.

Imaging Tests

Thyroid Scintigraphy. Thyroid scintigraphy tests scan the thyroid and pick up images highlighted by small amounts of radioactive substances. Thyroid scans can be used to determine whether the thyroid is producing normal amounts of hormone. The patient drinks a small amount of radioactive iodine or technetium and waits until the substance has passed through the thyroid. Images of a properly functioning thyroid would show uniform levels of absorption throughout the gland. Overactive areas show up white, and underactive areas appear dark. Thyroid scans are usually unnecessary unless the doctor needs to rule out suspected cancer.

Ultrasound. Ultrasound has limited value, but it can visualize the thyroid and specific abnormalities, such as nodules. (It cannot measure the thyroid gland's function, however.)

Click the icon to see an image of thyroid ultrasound.

More Advanced Imaging Tests. If laboratory tests suggest that a pituitary or hypothalamus problem is causing hypothyroidism, the doctor will usually order brain imaging procedures using computed tomography (CT) scans or magnetic resonance imaging (MRI). MRIs may also be used for determining the extent of thyroid cancers and of goiters. MRIs are also being used for investigating hypothyroidism in infants and for determining widespread effects of autoimmune thyroiditis (such as Hashimoto's hypothyroidism).

Needle Aspiration Biopsy

Needle aspiration biopsy is used to obtain thyroid cells for microscopic evaluation. It may be useful to rule out thyroid cancer in patients with suspected Hashimoto's hypothyroidism, especially if they have difficulty swallowing or develop a goiter. Much like drawing blood, the doctor injects a small needle into the thyroid gland and draws cells from the gland into a syringe. The cells are put onto a slide, stained, and examined under a microscope.

Other Blood Tests

Cholesterol levels need to be checked. Other blood tests may be performed to detect levels of calcitonin, calcium, prolactin, and thyroglobulin and to check for anemia and liver function, all of which may be affected by hypothyroidism.

Screening Recommendations for Hypothyroidism

Screening in Older Adults. Some doctors believe that because thyroid problems are so common in the elderly and thyroid hormone tests are so inexpensive, blood tests for thyroid function should be routine. Undiagnosed hypothyroidism in elderly patients can develop into a serious and even life-threatening situation. Hyperthyroidism also poses many health risks. In fact, during the period around menopause, the symptoms of menopause and hypothyroidism are similar and can easily be confused with each other.

Professional organizations differ widely on screening recommendations. Most do not recommend widespread screening for healthy adults:

• The American College of Physicians recommends that women over 50 years old be screened for thyroid disorders every 5 years. The American Academy of Family Physicians believes that adults do not have to be screened until they are over 60.
• The American Thyroid Association, however, recommends that all adults, both men and women, begin their screening at age 35 and every 5 years thereafter. Experts in this organization argue that such early screening is inexpensive and would prevent progression to hypothyroidism, and therefore possibly heart disease, in people with subclinical hypothyroidism. Such an approach would also eliminate the need for expensive anti-cholesterol drugs.

Screening in Pregnant Women. Untreated hypothyroidism in a pregnant woman, particularly in the first trimester, may cause premature delivery and birth defects. Birth defects can affect a babys intelligence, mental development, and motor skills. Subclinical hypothyroidism also increases the risk for premature delivery and birth defects.

Some experts propose that screening be done on any woman who is planning a pregnancy to help determine those who may be at increased risk for hypothyroidism and, if needed, begin treatment as early as possible during the critical first trimester. Women who have a personal or family history of hypothyroidism should have their thyroid checked within the first weeks of pregnancy and should be retested during each trimester.

Screening in Infants. It is very difficult to diagnose hypothyroidism in newborns by symptoms alone. Fortunately, almost all newborns with hypothyroidism are identified shortly after birth through an effective national screening program using a thyroid blood test.

Ruling Out Other Disorders

Because the symptoms of hypothyroidism are so similar to common conditions, including aging, diagnosis can be difficult.

Conditions That Cause Thyroid Abnormalities. Some conditions may cause thyroid abnormalities without symptoms and must be differentiated from subclinical hypothyroidism. They include, although are not limited to:

• Inadequate response to thyroid therapies in people with hypothyroidism
• Recovery from a severe illness that is unrelated to thyroid disorders
• Chronic kidney failure
• Failure of the adrenal gland

Aging-Related Disorders. Some symptoms of hypothyroidism and aging are very similar. Menopausal symptoms often resemble hypothyroidism. Many other problems related to aging -- such as vitamin deficiencies, Parkinson's and Alzheimer's diseases, and arthritis -- also have characteristics that can mimic hypothyroidism.

Obesity. Many people who are overweight believe that they have an underactive thyroid gland, but only a very small percentage of obese people actually have hypothyroidism. Patients with hypothyroidism generally show only a moderate weight increase of 5 - 10 pounds, mainly from accumulation of fluid, and in fact they often have a decreased appetite.

Depression. A lack of interest in personal relationships, drowsiness, an increase in sleep, slowing of speech, and general apathy are signs of clinical depression as well as hypothyroidism. The two disorders often coexist, particularly in older women, so diagnosing one does not rule out the presence of the other.

Diseases of Muscles and Joints. Joint and muscle aches may be the first symptoms of hypothyroidism. Most likely, however, such pain is not caused by hypothyroidism if other thyroid symptoms remain absent. Numerous conditions can cause muscle and joint pain, and if thyroid levels are normal the doctor should look for other causes.

Risk Factors

About 15 million Americans have unrecognized thyroid disease, mostly subclinical hypothyroidism (mildly underactive thyroid). Less than 2% of the U.S. population has full-blown hypothyroidism.

Women. Women have 10 times the risk of hypothyroidism as men, with the difference being significant after age 34. In one study, nearly 6% of women over 60 had hypothyroidism, and some experts estimate that as many as 20% of women in this age group have a subclinical condition. Because the symptoms of hypothyroidism and menopause are so similar, hypothyroidism may easily be missed.

Pregnancy is a major factor in the higher risk in women. It affects the thyroid in a number of ways and poses a high risk for hypothyroidism, both during pregnancy and afterward. For one, iodine requirements are high in both the mother and the fetus. Changes in reproductive hormones also cause changes in thyroid hormone levels. In addition, some women develop antibodies to their own thyroid during pregnancy, causing a condition known as postpartum autoimmune, or subacute, thyroiditis. This occurs in up to 10% of pregnant women and tends to develop between 4 - 12 months after delivery. It is a limited condition and nearly always clears up. However, it does pose a risk for the development of permanent hypothyroidism later on.

Age. The elderly are most susceptible, but hypothyroidism can affect people of all ages. For example, 1 in every 3,000 - 4,000 infants is born with congenital hypothyroidism. Female infants are at higher risk than males.

Ethnicity. African-Americans may be less likely to have thyroid disease than Caucasians and Asians.

Genetic Defects

Genetics plays a role in many cases of underactive and overactive thyroid. The genetics involved with hypothyroidism are complicated, however. Certain genetic features, for example, appear to play a role in Hashimoto's thyroiditis and postpartum thyroiditis in Caucasians, but others affect different ethnic groups. Thyroid disease will often skip generations. For example, someone with an underactive thyroid may have healthy parents but have grandparents who had thyroid troubles. Some people inherit a tendency to thyroid problems but never become ill, while others become very sick.

Smoking

Smoking significantly increases risk for thyroid disease, particularly autoimmune Hashimoto's thyroiditis and postpartum thyroiditis. Chemicals in cigarette smoke called thiocyanates appear to have especially harmful effects on the thyroid. Smoking also increases the negative effects of hypothyroidism, notably on the arteries and heart.

Medical Conditions Associated with Hypothyroidism

People with certain medical conditions have a higher risk for hypothyroidism. These conditions include:

• Autoimmune diseases. People with many autoimmune diseases have a higher risk for hypothyroidism. Type 1 (insulin-dependent) diabetes poses a higher risk and is a special problem since hypothyroidism can affect insulin requirements. Women with other autoimmune diseases, including systemic lupus erythematosus, pernicious anemia, and rheumatoid arthritis, are also at higher risk for hypothyroidism. Pregnant women with autoimmune conditions have a 25% risk for hypothyroidism during gestation.
• Breast cancer. There may be a link between breast cancer and thyroid levels, but the evidence is unclear. Some studies have indicated that women with breast cancer may be more susceptible to hypothyroidism. Other studies suggest the opposite. Several studies indicate that hypothyroidism itself may protect against breast cancer. In addition, when women with hypothyroidism develop breast cancer, it is often a less aggressive and more easily treated form.
• Gout. Hypothyroidism and gout often coexist and may have biologic mechanisms in common.
• Addison's disease.
• Myasthenia gravis.
• Polycystic ovarian syndrome.
• Anorexia or bulimia. People with eating disorders are at risk for hypothyroidism. In these cases, however, reduced thyroid function may be an adaptation to malnutrition and, therefore, some experts think that only the eating disorder should be treated, not hypothyroidism.
• Turner syndrome. As many as half of patients with Turner syndrome have hypothyroidism, usually in the form of Hashimoto's thyroiditis. This inherited condition is one of the most common genetic diseases in women.
• Glaucoma. A 2004 study of male veterans suggested that hypothyroidism may be associated with increased risk for developing open-angle glaucoma.

Click the icon to see an animation about gout.

Click the icon to see an image of polycystic ovarian syndrome.

Many drugs affect the thyroid, so anyone being treated for a chronic disease, patients who are taking thyroid medication, and those who are at risk for a thyroid disorder should discuss the impact these drugs may have on their thyroid.

Physical Factors Associated with Hypothyroidism Factors

Hypothyroidism is associated with premature gray hair and left-handedness.

Complications

Hypothyroidism carries serious physical and mental risks for all ages. Studies indicate that subtle adverse health effects occur even with subclinical hypothyroidism, a condition in which the patient has no symptoms but blood tests indicate hypothyroidism. Fortunately, hypothyroidism is now easily diagnosed, and treatment will restore normal thyroid function and relieve symptoms and physical signs of the disease. With treatment, a patient should expect to live a normal life, free of harmful consequences. Iodine deficiency and goiter are still major problems in less developed nations and cause varying degrees of mental retardation in millions of people.

Emergency Conditions

Myxedema Coma. Myxedema coma is a rare, life-threatening complication of untreated hypothyroidism. Symptoms include a severe drop in body temperature (hypothermia), delirium, reduced lung function, slow heart rate, constipation, urine retention, seizures, stupor, fluid build-up, and finally coma. It is uncommon, but may develop in untreated patients subjected to severe stress, such as infection, surgery, or extreme cold. Certain drugs (such as sedatives, painkillers, narcotics, amiodarone, and lithium) may increase the risk. Emergency treatment is required. Mortality rates are high (between 30 - 60%) with the highest risks in older patients and those with persistent hypothermia or heart problems.

Suppurative Thyroiditis. Suppurative thyroiditis is a life-threatening infection of the thyroid gland. It is very rare, since the thyroid is normally immune to infection. People with pre-existing thyroid diseases, such as Hashimoto's thyroiditis, however, may be at higher than average risk for it. It often begins with an upper respiratory infection. Symptoms include fever, neck pain and rash, and trouble swallowing and speaking. Immediate treatment is critical.

Effects of Hypothyroidism and Subclinical Hypothyroidism on the Heart

Thyroid hormones, notably triiodothyronine (T3), affect the heart directly and indirectly. They are closely linked with heart rate and heart output. T3 provides particular benefits by relaxing the smooth muscles of blood vessels. This helps keep the blood vessels open so that blood flows smoothly through them.

Hypothyroidism is associated with:

• Unhealthy cholesterol levels. Hypothyroidism raises levels of total cholesterol, LDL (the so-called bad cholesterol), triglycerides, and other lipids (fat molecules) associated with heart disease. Treating the thyroid condition with thyroid replacement therapy can significantly reduce these levels.
• Mild high blood pressure. Hypothyroidism may slow the heart rate to less than 60 beats per minute, reduce the heart's pumping capacity, and increase the stiffness of blood vessel walls. All of these effects may lead to high blood pressure. Indeed, patients with hypothyroidism have triple the risk of developing hypertension. All patients with chronic hypothyroidism, especially pregnant women, should have their blood pressures checked regularly.
• Heart failure. Hypothyroidism can affect the heart muscles contraction and increase the risk of heart failure in people with existing heart disease.

The evidence for subclinical hypothyroidism and heart disease is mixed. Some studies suggest that subclinical hypothyroidism increases the risks for coronary artery disease and heart failure. A 2007 study indicated that low-normal thyroid function may increase the risk for metabolic syndrome (a cluster of symptoms that include abdominal obesity, high blood sugar, and unhealthy cholesterol levels). However, a 2006 study in the Journal of the American Medical Association found that while subclinical hypothyroidism was associated with atrial fibrillation (irregular heart beat), it was not associated with other types of heart disease. Many experts believe that treatment of subclinical hypothyroidism will not help prevent or improve heart problems. More research is underway.

Effects of Hypothyroidism and Subclinical Hypothyroidism on the Mind

Depression. Depression is common in hypothyroidism and can be severe. Some psychiatrists suspect that even subclinical hypothyroidism may contribute to depression. The two disorders may have some common physiological basis. Adding thyroid hormones to antidepressants may hasten a depressed patient's recovery, even in some patients who have not been diagnosed with hypothyroidism. Hypothyroidism should be considered as a possible cause of any chronic depression, particularly in older women.

Mental and Behavioral Impairment. Untreated hypothyroidism can, over time, cause mental and behavioral impairment and eventually, even dementia. Whether treatment can completely reverse problems in memory and concentration is uncertain, although many experts believe that only mental impairment in hypothyroidism that occurs at birth is permanent.

A 2006 study of nearly 6,000 people age 65 years and older concluded that subclinical hypothyroidism is not associated with depression, anxiety, or mental impairment in elderly patients.

Other Health Effects of Hypothyroidism

The following medical conditions have been associated with hypothyroidism. Often the causal relationship is not clear in such cases:

• Iron deficiency anemia.
• Respiratory problems.
• Kidney function.
• Glaucoma. (Some research has associated hypothyroidism with an increased risk for glaucoma.)
• Headache. (Hypothyroidism may worsen headaches in people predisposed to them.)
• Thyroid lymphoma. (Patients with Hashimoto's thyroiditis are at higher risk for this rare form of cancer.)
• Joint stiffness. (Women with hypothyroidism may actually have fewer problems with joint stiffness than women with normal thyroid.)

Effects of Hypothyroidism on Infertility and Pregnancy

Most women with hypothyroidism fail to produce eggs, and many younger women with hypothyroidism are diagnosed with the condition for the first time during a fertility evaluation. A pregnant woman with hypothyroidism has a fourfold risk for miscarriage. In one study, nearly 40% of women with a history of miscarriages and normal thyroid levels had antithyroid antibodies (immune factors that attack thyroid tissue). Those who continue to have hypothyroidism near the time of delivery are in danger of developing high blood pressure and premature delivery. They are also prone to postpartum thyroiditis, which is said to be a contributor to postpartum depression.

Effects of Hypothyroidism on Infants and Children

Children of Untreated Mothers. Children born to untreated pregnant women with hypothyroidism are at risk for impaired mental performance, including attention problems and verbal impairment. Studies on the effects on children of women with subclinical hypothyroidism are less clear, with some reporting lower IQs in such children and others reporting no significant problems.

Effects of Hypothyroidism During Infancy. Transient hypothyroidism is common among premature infants. Although temporary, severe cases can cause difficulties in neurologic and mental development.

Infants born with permanent congenital (inborn) hypothyroidism need to receive treatment as soon as possible after birth to prevent mental retardation, stunted growth, and other aspects of abnormal development (a syndrome referred to as cretinism). It has been estimated that untreated infants can lose up to three to five IQ points per month during the first year. An early start of lifelong treatment avoids or minimizes this damage. Even with early treatment, however, mild problems in memory, attention, and mental processing may persist into adolescence and adulthood.

Effects of Childhood-Onset Hypothyroidism. If hypothyroidism develops in children older than 2 years, mental retardation is not a danger, but physical growth may be slowed and new teeth delayed. If treatment is delayed, adult growth could be affected. Even with treatment, some children with severe hypothyroidism may have attention problems and hyperactivity.

Effects of Hypothyroidism and Childhood X-Ray Treatments

Two million Americans, mostly children, received x-ray treatments to the head or neck between 1920 - 1960 for acne, enlarged thymus gland, recurrent tonsillitis, or chronic ear infections. The risk of developing thyroid nodules and thyroid cancers is increased in these individuals, especially if they have hypothyroidism. Cancer can develop as late as 40 years after the original treatment. Everyone who has had head and neck radiation should be sure to have their thyroid glands examined regularly.

Treatment

Various tests are used when deciding whether to treat a patient for hypothyroidism:

• First, an elevated TSH (thyrotropin) level should be confirmed and thyroxine (T4) level determined.
• Testing for antithyroid antibodies and determining cholesterol levels is also important.

Treating Hypothyroidism. Patients with full-blown hypothyroidism, indicated by clear symptoms and blood tests that show high TSH (generally 10 mU/L and above) and low thyroxine (T4) levels, must be treated with thyroid replacement.

Treating Subclinical Hypothyroidism. Considerable debate exists about whether to treat patients with subclinical hypothyroidism (slightly higher than normal TSH levels, normal thyroxine levels, and no obvious symptoms). Some doctors opt for treatment because of the following benefits, although evidence remains uncertain:

• Preventing progression to full-blown hypothyroidism. Treating subclinical hypothyroidism will prevent progression to overt hypothyroidism. Only a minority of people with subclinical hypothyroidism go on to develop the active condition, however.
• Preventing heart disease. Some studies have shown that treating subclinical hypothyroidism lowers cholesterol levels and may improve other heart functions, including blood pressure, endothelial function, and heart rate. However, current research from 2006 suggests that subclinical hypothyroidism poses little risk for heart disease and that untreated subclinical hypothyroidism will not increase heart disease risks.
• Improving well-being. Some studies report that treating subclinical hypothyroidism may improve mild psychological symptoms, such as impaired mental functioning and depression. About 25% of patients with subclinical hypothyroidism report feeling better after taking thyroid medication even if they have not previously reported symptoms.

It is not clear, then, if the benefits of treating subclinical hypothyroidism outweigh the higher costs of testing and treatments. Experts against treatment argue that thyroid levels can vary widely, and subclinical hypothyroidism may not persist. In such cases, overtreatment leading to hyperthyroidism is a real risk.

In spite of such uncertainties, three out of four major medical organizations recommend treatment for subclinical hypothyroidism, particularly in patients who have:

• High total or LDL cholesterol levels
• Blood tests that show autoantibodies indicating a future risk for Hashimoto's thyroiditis or other forms of other autoimmune hypothyroidism
• Blood tests that show TSH levels greater than 10 mU/L
• Goiter

Experts also recommend treating subclinical hypothyroidism in:

• Pregnant women
• Women with infertility that may be associated with subclinical hypothyroidism

Treatment is optional in patients with subclinical hypothyroidism who have no obvious symptoms and normal cholesterol levels. If they forego treatment, however, they should be tested yearly for TSH and thyroxine.

Treating Patients with Hypothyroidism Symptom and Normal Thyroid Tests. Some doctors treat patients who have a normal or below normal thyroid function test. Some experts believe it is irresponsible to treat such patients with thyroid replacement since such symptoms can occur with many physical and psychological conditions. In any case, studies have not found any benefits from T4 replacement therapies in this group.

Thyroid Hormone Replacement

In the 19th century, doctors observed the relationship between myxedema (swelling of the hands, face, feet, and tissues around the eyes) and surgical removal of the thyroid gland. Some doctors began to feed patients with myxedema with whole or powdered extracts of animal thyroid glands. Using thyroid hormone to treat hypothyroidism was one of the first successful medical treatments based on careful scientific observation. With only some modifications, this approach has varied little for over a century.

A synthetic thyroid hormone called levothyroxine is currently the treatment of choice for hypothyroidism. This drug is a synthetic derivative of T4 (thyroxine), and it normalizes blood levels of TSH, T4, and T3. Nevertheless, the therapeutic principle for hypothyroidism is the same as it was more than 100 years ago: To provide the body with replacement thyroid hormone when the gland is not able to produce enough itself.

Brand Names. A number of levothyroxine brands are available in the U.S. and overseas. Synthroid is the oldest brand and has been used for over 40 years. In the past, manufacturers of levothyroxine have not had to meet as strict standards as in the production of other drugs. This resulted in thyroid products with varying quality. The FDA has issued stronger requirements that have largely corrected this problem.

Generics versus Brand-Name Products. Generic brands are available and are subject to the same guidelines as brand-name products. There is still considerable debate over whether generic thyroid preparations are as effective as brand products.

In addition, the amount of T4 in some generic products is outside the FDA range, which requires additional testing of thyroid hormone levels. Many doctors, then, prefer to use brand-name products, noting that the cost difference between brand and generic thyroid drugs is not substantial. Regardless of which type is used, once a patient has been stabilized, doctors generally recommend sticking with one type or brand since potency often varies from one drug to the next.

Natural Thyroid Hormone. Dried powdered thyroid hormone (Armour Thyroid, S-P-T, Thyrar, Thyroid Strong) is made from animal glands. It was once the most common form of thyroid therapy but is no longer generally recommended because potency varies. Some people argue that with stricter FDA regulations, this natural form is better controlled and may even reduce the risk of developing autoimmunity factors. Dried thyroid also contains both T3 and T4 and is favored as a natural treatment by many alternative practitioners. However, studies need to be conducted to evaluate its benefits.

T3 and T4 Combinations. Triiodothyronine (T3), the other important thyroid hormone, is not ordinarily prescribed except under special circumstances. Most patients respond well to thyroxine (T4) alone, which is converted in the body into T3. In addition, the use of T3 may cause disturbances in heart rhythms. Some patients treated only with thyroxine continue to have mood and memory problems or other symptoms.

Combination products containing T4 and T3, such as liotrix (Thyrolar), are available, but there is some controversy concerning their benefits. Several 2005 studies suggested that although some patients may prefer combination therapy, T3 and T4 together do not work better than T4 alone. Patients might like the combined drugs because they cause more weight loss, or a placebo effect may be involved. It does not appear that combination products offer any advantage for normalizing TSH levels.

Levothyroxine Regimens

Levothyroxine only needs to be taken once a day. It is slowly assimilated by body organs, so it usually takes up to 6 weeks before symptoms improve in adults. Nevertheless, many patients feel better after 2 - 3 weeks of treatment. The speed at which specific symptoms improve varies:

• Weight loss, less puffiness, and improved pulse usually occur early in the treatment.
• Improvements in anemia and skin, hair, and voice tone may take a few months.
• High LDL ("bad cholesterol") levels decline very gradually. HDL ("good cholesterol") levels are not affected by treatment.
• Goiter size declines very slowly, and some patients may require high-dose thyroid hormone (called suppressive thyroid therapy) for a short period.

Levothyroxine reduces blood pressure in about half of hypothyroid patients with hypertension, although blood pressure medications may still be needed.

Appropriate Dosage Levels. Initial dosage levels are determined on an individual basis and can very wide depending on a person's age, medication condition, other drugs they are taking, and, in women, whether they are pregnant or not. For example, pregnant women with hypothyroidism may require higher than normal doses.

• Starting out. Most individuals need to build up gradually until they reach a maintenance dose. In uncomplicated cases, the dose typically starts at 50 micrograms per day, which then increases in 3- to 4-week intervals until thyroid hormone levels are normal. Seniors and those with heart disease may start at 12.5 - 25 micrograms per day. On the other hand, young adults with a short history of hypothyroidism might be able to tolerate a full maintenance dosage right away.
• Maintenance dose. Maintenance dose for most patients averages 112 micrograms but it can vary between 75 - 260 micrograms. If conditions such as pregnancy, surgery, or other drugs alter hormone levels, the patient's thyroid needs will have to be reassessed.

Daily Regimen. Because thyroid replacement is usually lifelong, setting up a regular daily routine is helpful. Here are some tips to remember:

• Establish a habit of taking the medication at the same time each day. This may help prevent missed doses.
• Levothyroxine is very forgiving. The hormone remains in the body for several days, so one missed dose should not cause a noticeable decline in well-being. The patient can safely take two doses the next day.
• Fiber and common daily supplements, such as calcium, may interfere with thyroxine absorption. Although levothyroxine can be taken at any time of day either with or without food, some experts recommend taking thyroid hormone upon awakening and at least 30 minutes before consuming anything, including breakfast or supplements.

Annual Evaluation. Thyroid failure is an ongoing process and so is its treatment. Many factors can cause changes that require modifying the thyroxine dosages.

A dose that is appropriate for 1 year may be too low the next. To maintain normal thyroid levels, some patients may need to take gradually increasing doses of thyroid hormone every year or two. Experts recommend that patients be reevaluated 6 months after normal TSH levels have been reached and then once a year thereafter.

Specific factors, such as changes in health or diet, new medications for other conditions, or simply switching brands, can also cause changes in thyroid hormone levels that require different doses. If patients change dose levels or thyroxine brands then they should be checked again at least 6 weeks later.

Problems Encountered with Levothyroxine Treatment

Because levothyroxine is identical to the thyroxine the body manufactures, side effects are rare. Over- or under-dosing, however, is fairly common, although rarely serious in the short term.

No Symptom Improvement When Normal Thyroid Levels Are Reached. Some patients fail to feel significantly better even when their thyroid levels become normal after taking thyroid replacement.

Some experts argue that many patients become symptom-free only if their thyroid replacement achieves high-normal T4 and low-normal TSH levels (rather than just normal levels). They believe that slightly higher thyroxine levels will not be harmful. Research is needed to confirm these claims.

Some patients with persistent symptoms may benefit from triiodothyronine (T3), the other important thyroid hormone. In such cases, either a combination of a lower-dose of thyroxine with a small amount of T3 or natural dried thyroid hormone, which contains T3, may be helpful.

Side Effects of Under-Dosing. If the levothyroxine dose is not sufficient to restore normal thyroid levels, or if the patient frequently forgets to take the medication, the patient may continue to experience symptoms of hypothyroidism. Even mild hypothyroidism without any symptoms can eventually lead to an increase in cholesterol levels. In a 2000 study, 40% of people taking thyroid medication still had abnormal levels of TSH. To avoid these problems, patients should take the proper dosage of levothyroxine as prescribed and have regular check-ups that include measurement of blood TSH.

Side Effects of Over-dosing: Thyrotoxicosis. Over-dosing can cause thyrotoxicosis, or the symptoms of hyperthyroidism. A patient with too much thyroid hormone in the blood is at an increased risk for abnormal heart rhythms, rapid heartbeat, congestive heart failure, and possibly a heart attack if the patient has underlying heart disease. Excess thyroid hormone is particularly dangerous in newborns, and their drug levels must be carefully monitored to avoid brain damage.

Side Effects of Long-Term Treatment. Patients with hypothyroidism usually receive lifelong levothyroxine therapy. There has been some concern that long-term use will increase the risk of osteoporosis, as suppression therapy does. Studies indicate that postmenopausal women who are taking long-term normal replacement thyroxine have no out-of-the-ordinary risk for osteoporosis.

Drug Interactions with Levothyroxine. Many drugs interact with levothyroxine and may either enhance or interfere with its absorption. These drugs include amphetamines, anticoagulants (blood thinners), tricyclic antidepressants, anti-anxiety drugs, arthritis medications, aspirin, beta-blockers, insulin, oral contraceptives, digoxin, and certain cancer drugs. Large amounts of dietary fiber may also reduce the drugs effectiveness. People whose diets are consistently high in fiber may require larger doses of the drug. Since thyroid hormones regulate the metabolism and can affect the actions of a number of medications, dosages may also need to be adjusted if a patient is being treated for other conditions. Even changing thyroxine brands can have a different effect.

Suppressive Thyroid Therapy

Suppressive thyroid therapy involves taking levothyroxine in doses that are high enough to block the production of natural TSH but too low to cause hyperthyroid symptoms. It may used for patients with large goiters or thyroid cancer.

Suppressive thyroid therapy places patients, particularly postmenopausal women, at risk for accelerated osteoporosis, a disease that reduces bone mass and increases risk of fractures. Some researchers suggest, however, that such bone loss is too slight to pose any significant risk for fracture. Furthermore, the cholesterol-lowering benefits of suppressive therapy outweigh this small risk. A small study found that premenopausal women taking suppressive therapy for more than 10 years were also at increased risk of bone loss by the time they reach menopause, although more research is needed to confirm this.

Bone density loss can be reduced or avoided by taking no higher a dose of thyroxine than necessary to restore normal thyroid function. In any case, doses of T4 must be continuously and carefully tailored in all patients to avoid adverse effects on the heart.

A number of medications are also available that can help preserve bone in postmenopausal women. Women on hormone replacement therapy may need to increase their dose of thyroid hormone.

Treatment of Special Cases

Treating the Elderly and Patients with Heart Disease. Thyroid dysfunction is common in elderly patients, with most having subclinical hypothyroidism. There is no evidence that this condition poses any great harm in this population, and some experts recommend treating only high-risk patients. One study suggested many elderly patients have been treated unnecessarily for hypothyroidism for years. In the study, half the patients taking thyroid hormone were taken off the medication successfully. Such patients may have been inappropriately diagnosed years ago, when testing was less accurate. More sensitive tests available now should reduce this risk.

Elderly patients, particularly people with heart conditions, usually start with lower doses of thyroid replacement, since a large initial dose may be a shock to the heart. Thyroid treatment may aggravate angina in about 20% of patients with the heart condition. About 40% of patients who have heart disease must take lower-than-average maintenance doses. Experts do not recommend treatment for subclinical hypothyroidism in elderly patients with heart disease whose test show only minimal thyroid hormone abnormalities and who have no anti-thyroid antibodies. Such patients should be closely monitored, however.

Preliminary research indicates that in patients undergoing cardiac bypass surgery, administration of triiodothyronine at the time of surgery may improve blood flow, heart rate, and cardiac output. Patients with advanced heart failure may also benefit from supplementary thyroid hormone.

Treating the Mentally Ill. Patients with psychiatric illness often forget to take their medications regularly. In these patients, once- or twice-weekly dosing of thyroid medications is often safe and effective and may improve compliance.

Treating Newborns and Infants with Hypothyroidism. Babies who are born with hypothyroidism (congenital hypothyroidism) should be treated with levothyroxine (T4) as soon as possible to prevent complications. Early treatment can help improve IQ and other developmental factors. However, even with early treatment, mild problems in mental functioning may persist into adulthood. In general, children who are born with milder forms of hypothyroidism will fare better than those who have more severe forms.

Single oral doses of levothyroxine (T4) can usually restore normal thyroid hormone levels within 1 - 2 weeks. It is critical that normal levels are achieved within a 2-week period. If thyroid function is not normalized within 2 weeks, it can pose greater risks for developmental problems. Some experts urge treating newborns at slightly higher than recommended doses for the first 2 weeks and then reducing the dosage once normal thyroid levels have been reached. Infants should continue to be monitored closely to be sure that thyroxine levels remain as consistently close to normal as possible. These children need to continue lifelong thyroid hormone treatments.

Treatment During Pregnancy and for Postpartum Thyroiditis. Women who have hypothyroidism before becoming pregnant may need to increase their dose of levothyroxine during pregnancy. In very rare cases, women may develop hypothyroidism while pregnant and need to be treated with levothyroxine in full replacement doses to reduce the risk of stillbirth. The developing baby is not affected when the pregnant woman takes thyroid hormones. The pregnant woman with hypothyroidism should be monitored regularly and doses adjusted as necessary. If postpartum thyroiditis develops after delivery, any thyroid medication should be reduced or temporarily stopped during this period.

Treatment for Myxedema Coma. Myxedema coma is an emergency situation, and the patient should be given intravenous doses of thyroid hormone, which could be triiodothyronine, levothyroxine, or both. Lower doses may be safer in elderly patients. Oftentimes, hydrocortisone, a corticosteroid, is also administered. Any other accompanying critical condition, including low body temperature, slow heart rate, low blood sugar, and difficulty in breathing, should also be treated immediately.

Treatment of Secondary Hypothyroidism. The small percentage of patients who have hypothyroidism due to a pituitary or hypothalamus problem should take levothyroxine along with their other medication to treat the primary disorder. In secondary hypothyroidism, the adrenal gland is often impaired. This means that the increased activity in the metabolic rate that occurs after thyroid replacement therapy may trigger a severe and even life-threatening condition called addisonian crisis, which is caused by a sudden demand for the depleted stress hormones secreted by the adrenal gland. Before administering thyroid replacement, the doctor should initiate a test that stimulates release of ACTH, one of the hormones secreted by the adrenal gland. If there is insufficient ACTH, then before thyroid replacement is started, the patient is usually treated with cortisone acetate, a stress hormone.

Taking Thyroid Hormone Inappropriately

In one study of those taking thyroid hormone, 12% of women and 29% of men took it inappropriately. In some cases of infertility, women with menstrual problems and repeated miscarriages and men with low sperm counts have been treated with thyroid hormones even when there was no evidence of thyroid abnormalities. (Women showing high levels of TSH, however, may benefit from levothyroxine therapy.)

Other inappropriate uses for thyroid hormones are for weight loss and to reduce high cholesterol levels. Thyroid hormones have also been given to treat so-called metabolic insufficiency. Vague symptoms suggesting low metabolism, such as dry skin, fatigue, slight anemia, constipation, depression, and apathy, should not be treated indiscriminately with thyroid hormone. No evidence exists that thyroid therapy is beneficial unless the patient has proven hypothyroidism. Indiscriminate use of thyroid hormones can weaken muscles and, over the long term, even the heart. One exception is the use of thyroxine to enhance drugs used for the treatment of severe depression.

Increased or Restricted Iodide Intake

Treating Hypothyroidism and Iodide Deficiency. People who are iodide deficient may be able to be treated for hypothyroidism simply by using iodized salt. In addition to iodized salt, seafood is a good source. Except for plants grown in iodine-rich soil, most other foods do not contain iodine. The current RDA for iodide is 150 micrograms for both men and women, with an upper limit of 1,100 micrograms to avoid thyroid injury.

Iodine Restriction in Patients with Hashimoto's Thyroiditis. Some evidence suggests that excess iodine triggers Hashimoto's thyroiditis. Small studies report that restricting iodine intake restored thyroid levels to normal in up to 75% of these patients. More research is needed.

Resources

• www.aace.com -- American Association of Clinical Endocrinologists
• www.thyroid.org -- American Thyroid Association
• www.tsh.org -- Thyroid Foundation of America
• www.endo-society.org -- Endocrine Society

References

Desai J, Yassa L, Marqusee E, George S, Frates MC, Chen MH, et al. Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med. 2006 Nov 7;145(9):660-4.

Roberts LM, Pattison H, Roalfe A, Franklyn J, Wilson S, Hobbs FD, et al. Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction? Ann Intern Med. 2006 Oct 17;145(8):573-81.

Roos A, Bakker SJ, Links TP, Gans RO, Wolffenbuttel BH. Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab. 2007 Feb;92(2):491-6.

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