Hypothyroidism
Highlights
What is Hypothyroidism?
Hypothyroidism, also called underactive thyroid, is a condition in which the thyroid gland does not produce enough hormone. Hypothyroidism can be caused by the autoimmune disorder Hashimotos thyroiditis, irradiation or surgical removal of the thyroid gland, and medications that reduce thyroid hormone levels. Anyone can develop hypothyroidism, but people who are most at risk include those who are over age 50 and female. However, only a small percentage of people have full-blown (overt) hypothyroidism. Many more have mildly underactive glands (subclinical hypothyroidism).
Symptoms
Early symptoms of hypothyroidism include:
- Chronic fatigue
- Difficulty concentrating
- Sensitivity to cold
- Headache
- Muscle and joint aches
- Weight gain, despite diminished appetite
- Constipation
- Dry skin
- Early puberty
- Menstrual irregularities (either heavier-than-normal or lighter-than-normal bleeding)
- Milky discharge from the breasts (galactorrhea)
Diagnosis and Treatment
Hypothyroidism can cause serious complications if left untreated. Fortunately, it can be easily diagnosed with blood tests that measure levels of thyroxine (T4) and thyroid-stimulating hormone (TSH). The doctor may also want to test for antithyroid antibodies and check your cholesterol levels. Based on these test results, the doctor will decide whether to prescribe medication or simply have the patient get lab tests every 6 - 12 months.
Medications
The standard drug treatment for hypothyroidism is a daily dose of a synthetic thyroid hormone called levothyroxine. This drug helps normalize blood levels of T4, TSH, and a third thyroid hormone called triidothyronine(T3). Many prescription medications can interact with levothyroxine and either increase or decrease its potency. (Be sure your doctor knows all medications you are currently taking.) Large amounts of dietary fiber can also interfere with levothyroxine treatment. People who eat high-fiber diets may require higher doses of the drug.
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.
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.
Hypothyroidism is separated into either overt or subclinical disease. That diagnosis is determined on the basis of the TSH laboratory blood tests. The normal range of TSH concentration falls between 0.45 - 4.5 mU/L.
- Patients with mildly underactive (subclinical) thyroid have TSH levels of 4.5 - 10mU/L.
- Patients with levels greater than 10mU/L are considered to have overt hypothyroidism and should be treated with medication.
Subclinical, or mild, 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.
Mildly underactive thyroid does not progress to the full-blown disorder in most people. Experts estimate that each year about 2 - 5% of people with subclinical thyroid 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.
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).
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 have 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. If so, therapy may be thyroxine replacement for a few months. A doctor will prescribe beta-blockers if the hyperthyroid phase needs 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.
Post-Treatment of Hyperthyroidism
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
Patiens 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.
Click the icon to see an illustrated series detailing thyroid removal.
A small percentage of Graves disease patients 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 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.
Other Medical Conditions
A variety 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.
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 and Complaints. Early symptoms of hypothyroidism are subtle and, in older people, can be easily mistaken for symptoms of stress or aging. They include:
- Chronic fatigue
- Difficulty concentrating
- Sensitivity to cold
- Headache
- Muscle and joint aches
- Weight gain, despite diminished appetite
- Constipation
- Dry skin
- Early puberty
- Menstrual irregularities (either heavier-than-normal or lighter-than-normal bleeding)
- Milky discharge from the breasts (galactorrhea)
In premenopausal women, early symptoms can interfere with fertility. 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, other symptoms may be present depending on what part of the pituitary gland may be involved and how large the tumor is. Symptoms of secondary hypothyroidism include:
- Sexual drive and fertility may be impaired in both men and women
- Galactorrhea (milky discharge from the breasts)
- Patients may feel exhausted, crave salt, and have low blood pressure
- Headaches and visual disturbances may develop
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 untreated hypothyroidism 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 need thyroxine (T4) replacement therapy. They should also be tested for high cholesterol levels and antithyroid antibodies.
- Levels between 4.5 - 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 - 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 need 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 - 10 mU/L). Thyroxine therapy is usually needed if antibody levels are high, since high levels indicate an underlying autoimmunity condition that poses a high risk for later thyroid failure. If tests are negative but the patient has thyroid-related problems (such as high cholesterol or female infertility), the patient needs annual hormone tests.
About 10% of the American population and 25% of women over 60 years old carry these antibodies, the majority of these women having 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.
- The U.S. Preventive Task Force recommends against routine screening for thyroid disease in adults.
Screening in Pregnant Women. Untreated overt 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 may increase the risk for premature delivery but does not seem to be associated with neurologic or developmental outcomes in children.
Current guidelines recommend targeting screening of women before or during pregnancy based on symptoms or history. Factors that suggest screening is indicated include: History of thyroid disease, goiter, type 1 diabetes or other autoimmune illnesses, history of miscarriages, and history of head and neck radiation or surgery. Women with these factors should have their thyroid checked before pregnancy, or 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:
- 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 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 risk for hypothyroidism is greatest after age 50 and increases with age. However, 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 for 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.
- 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 patients, 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.
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, taking thyroid medication, and those at risk for a thyroid disorder should discuss the impact these drugs may have on their thyroid.
Complications
All patients with hypothyroidism are at serious risk for physical and mental problems. 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 (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 suppurative thyroiditis. It often begins with an upper respiratory infection. Symptoms include fever, neck pain, 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 pressure checked regularly.
- Heart failure. Hypothyroidism can affect the heart muscles contraction and increase the risk of heart failure in people with 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. The only randomized controlled trial dealing with subclinical hypothyroidism and heart disease evaluated only the thickness of atherosclerosis in the blood vessels and not whether patients actually had clinical heart disease. Many doctors 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 overt hypothyroidism have menstrual cycle abnormalities and often fail to ovulate. A pregnant woman with hypothyroidism has a fourfold risk for miscarriage. Overt hypothyroidism in a pregnant woman can affect normal fetal development.
The presence of antithyroid antibodies (immune factors that attack thyroid tissue), especially when associated with abnormal TSH thyroid levels, can lead to an increased risk of miscarriages. Women who 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 may 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 have their thyroid glands examined regularly.
Treatment
A variety of factors affect the decision of whether to treat a patient for hypothyroidism, which dosage to begin with, and how rapidly treatment should be started or increased:
- First, an elevated TSH (thyrotropin) level should be confirmed and thyroxine (T4) level determined. Other thyroid tests may also be helpful.
- Measuring cholesterol levels is also important.
Doctors should also consider:
- Age of the patient
- Presence of other medical problems that may benefit from thyroid replacement treatment (such as heart failure or depression)
- Presence of other medical problems that thyroid replacement therapy may worsen (such as osteoporosis)
Treating Overt Hypothyroidism. Patients with overt hypothyroidism, indicated by clear symptoms and blood tests that show high TSH (generally 10 mU/L and above) and low thyroxine (T4) levels, must have thyroid replacement therapy.
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 and others opt for simply monitoring patients.
It is not clear 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.
There is reasonable evidence and consensus to recommend treatment for subclinical hypothyroidism in the presence of other factors, including:
- 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
- Pregnancy
- Female infertility associated with subclinical hypothyroidism
Treatment is optional in patients with subclinical hypothyroidism who have no obvious symptoms and normal cholesterol levels. Some doctors feel that treating this group of patients will prevent progression to overt hypothyroidism and future heart disease, as well as increase a patient's sense of well-being. However, the evidence to support treatment of this patient group is not nearly as strong. Many doctors recommend against treatment and suggest that these patients should simply have lab tests every 6 - 12 months.
Treating Patients with Hypothyroidism Symptoms 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 from many physical and psychological conditions. In any case, studies have not found any benefits from T4 replacement therapies in this group.
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.
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 tests show only minimal thyroid hormone abnormalities and who have no anti-thyroid antibodies. Such patients should be closely monitored, however.
Preliminary research indicates that patients undergiong cardiac bypass surgery may benefit from having triiodothyronine at the time of surgery, to 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 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 last into adulthood. In general, children 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. Women who are first diagnosed with overt hypothyroidism during pregnancy should be treated immediately, with quick acceleration to therapeutic levels. Although not well proven, most doctors recommend treating patients diagnosed with subclinical hypothyroidism while pregnant. There are no risks to the developing baby when the pregnant woman takes appropriate doses of 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. Hydrocortisone, a corticosteroid, is also often 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.
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 is stable, 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 (such as Armour Thyroid, S-P-T, Thyrar, and 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 needs to be taken only 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 need 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 widely, depending on a person's age, medication condition, other drugs they are taking, and, in women, whether or not they are pregnant. For example, pregnant women with hypothyroidism may need higher than normal doses.
- Starting out. Most people 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 eating 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 one 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, 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.
Symptoms of Under- and Over-Dosing of Levothyroxine | |
Under-Dosing | Over-Dosing |
Sluggishness | Heart symptoms (rapid heart beat, palpitations, and wide variations in pulse; possible angina or congestive heart failure) |
Mental dullness | Agitation (tremor, nervousness, insomnia, excessive sweating) |
Feeling cold | Pain (headache and muscle pain) |
Muscle cramps | Intestinal and metabolic symptoms (change in appetite, diarrhea, weight loss) |
Fever and intolerance to heat | |
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 Underdosing. 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 Overdosing: Thyrotoxicosis. Overdosing 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, 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
- Certain cancer drugs
- Iron replacement therapy (ferrous sulfate)
- Calcium carbonate and aluminum hydroxide
- Anticonvulsants (phenytoin, phenobarbital, carbamazepine)
- Rifampin (antibiotic used to treat or prevent tuberculosis)
Large amounts of dietary fiber may also reduce the drugs effectiveness. People whose diets are consistently high in fiber may need 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.
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.hormone.org -- Hormone Foundation
- www.endo-society.org -- Endocrine Society
References
Abalovich M, Amino N, Barbour LA, Cobin RH, De Groot LJ, Glinoer D, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2007 Aug;92(8 Suppl):S1-47.
American Academy of Pediatrics, Rose SR; Section on Endocrinology and Committee on Genetics, American Thyroid Association, Brown RS; Public Health Committee, et al. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006 Jun;117(6):2290-303.
Ladenson P, Kim M. Thyroid. In: Goldman L and Ausiello D, eds. Cecil Medicine. 23rd ed. Saunders; 2007:chap 244.
Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab. 2007 May;92(5):1715-23. Epub 2007 Feb 13.
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.
Rodondi N, Aujesky D, Vittinghoff E, Cornuz J, Bauer DC. Subclinical hypothyroidism and the risk of coronary heart disease: a meta-analysis. Am J Med. 2006 Jul;119(7):541-51.
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.
Villar HC, Saconato H, Valente O, Atallah AN. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD003419.
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
