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Hypothyroidism

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of hypothyroidism.

Alternative Names

Autoimmune Thyroiditis; Hashimoto's Thyroiditis

Treatment

Various tests come into play 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. It is well established that 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 are normal, and no obvious symptoms). Many physicians now 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 are showing that treating subclinical hypothyroidism lowers cholesterol levels and may improve other heart functions, including blood pressure and heart rate. (It should be noted, however, that there is no strong evidence yet that subclinical hypothyroidism harms the heart or increases mortality rates.)
  • Improving well-being. Some, but not all 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 the following patients with this condition:

  • People with high total or LDL cholesterol levels.
  • People with blood tests that show autoantibodies indicating a future risk for Hashimoto's thyroiditis or other forms of other autoimmune hypothyroidism.
  • People without symptoms but who have blood tests showing TSH levels greater than 10 mU/L.
  • People with goiter.
  • Pregnant women, regardless of whether they have symptoms, antithyroid antibodies, or high cholesterol.
  • 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 physicians 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, well-conducted studies have not found any benefits from T4 replacement therapies in this group.

Thyroid Hormone Replacement

In the nineteenth century, physicians observed the relationship between myxedema (swelling of the hands, face, feet, and tissues around the eyes) and surgical removal of the thyroid gland. Some physicians, then, 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 US and overseas. Synthroid is the oldest brand and has been used for over 40 years. In the past, manufactures 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. For example, brand-name products come in up to 12 different strengths, while generics have less variety from which to choose. Generic brands then may not be appropriate for patients with conditions requiring frequent adjustment of dosages. In addition, the amount of T4 in some generic products is outside the FDA range, which requires additional testing of thyroid hormone levels. Many physicians, then, prefer to use brand-name products, further 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, physicians generally recommend sticking with one type or brand since potency often varies from one drug to the next.

Natural Thyroid Hormone. Desiccated or 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. Desiccated 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 the body normally converts into the more biologically active T3 form. In addition, the use of T3 may cause disturbances in heart rhythms. Still, some patients treated only with thyroxine continue to have mood and memory problems or other symptoms. In one study, patients given a synthetic form of T3 called liothyronine (Cytomel, Triostat) plus a slightly lower-than-normal dose of levothyroxine reported improved symptoms compared to T4 alone. The study was small, however, and patients were severely hypothyroid and may have been lacking T3 in the first place. It is possible that some patients who do not respond to thyroxine may not be able to properly convert T4 to T3. Combination products containing T4 and T3, such as liotrix (Thyrolar), are available. Some mental health practitioners are also examining giving combination treatments for hypothyroid patients with resistant depression or bipolar disorder. However, these products have not been rigorously tested in different patient groups, and more work is needed before this combination is recommended widely.

Levothyroxine Regimens

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

  • Weight loss, less puffiness, and improved pulse usually occur early into the treatment.
  • Improvements in anemia and skin, hair, and voice tone may take a few months.
  • High LDL cholesterol levels decline very gradually. (HDL levels, the so-called good cholesterol, 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.

It should be noted that 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 they can very wide depending on the 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 three- to four-week intervals until thyroid hormone levels are normal. Seniors and those with heart disease may start at 12.5 to 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 and 260 micrograms. If conditions, such pregnancy, surgery, or taking certain 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 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 six 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 the patient changes dose levels or thyroxine brands then he or she should be checked again at least six weeks following such changes.

Problems Encountered with Levothyroxine Treatment

Because levothyroxine is identical to the thyroxine the body manufactures, side effects are nearly unheard of. 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 desiccated Armour thyroid hormone, which contains T3, may be helpful.

There is the possibility that patients with an autoimmune thyroid condition may have persistent symptoms because of the inflammatory response that underlies this condition. This immune response can cause feelings of fatigue, vague aches and pains, and other symptoms that are similar to hypothyroidism itself. Little research has been conducted on this theory, however.

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 one 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.

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. (Of note was a 2000 study reporting that radioactive iodine may be an effective alternative for patients with benign goiters and may have fewer side effects.)

A number of medications are also available that can help preserve bone in postmenopausal women. Note, however, that women on hormone replacement therapy may need to increase their dose of thyroid hormone. [For more information, seeWell-Connected Report #40, Menopause, Estrogen Loss, and Their Treatments.]

Drug Interactions with Levothyroxine. Many substances and conditions interact with levothyroxine and may either enhance or interfere with its absorption. Large amounts of dietary fiber may also reduce its action. 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 need to be adjusted if a patient is being treated for other conditions. Even changing thyroxine brands can have a different effect.

Examples of Drug Interactions with Thyroid Hormone

Drugs that Inhibit Thyroid Hormone

Drugs that are Enhanced by Thyroid Hormone

Drugs that are Suppressed by Thyroid Hormone

Drugs that Reduce Natural Thyroid Hormone Levels and May Cause Hypothyroidism

Iron supplements (even low doses found in multivitamins).

Calcium carbonate supplements.

Aluminum-containing antacids (e.g., Maalox).

Drugs used to reduce cholesterol levels by binding bile acids. Include colestipol (Colestid) and cholestyramine (Questran). Take four to five hours apart.

Estrogens in oral contraceptives and hormone replacement therapy. May need to increase thyroid hormone while taking estrogen. Need to monitor thyroid after withdrawal from estrogen.

Raloxifene (Evista), a designer-estrogen used for osteoporosis. (Evidence suggests interaction is weak.)

Sucralfate (Carafate). Take at least two hours apart.

Epinephrine (adrenaline) injections. Thyroid hormone may increase the risk of serious side effects in heart disease patients given this agent.

Warfarin, a blood thinner. Doses of this medication may need to be reduced if thyroid treatment is started after blood thinning treatments have begun.

Many antidepressants. In some cases, potency of both antidepressants and thyroid hormones may increase.

Diabetic Drugs. Diabetic patients taking thyroid hormone may need additional insulin or oral hypoglycemic drugs. Stopping or reducing thyroid hormone may increase the risk of hypoglycemia.

Digoxin. Patients with heart disease may need to increase their dosage of digoxin (Lanoxin).

Lithium. This drug, used in bipolar disorders, has multiple effects on thyroid hormone synthesis and secretion.

Amiodarone (Cordarone). This drug, used to treat abnormal heart rhythms, contains iodine and can induce hyper- or hypothyroidism, particularly in patients with an existing thyroid problem.

Antiseizure drugs used for epilepsy, including phenytoin and carbamazepine.

Interferons and interleukins used in hepatitis, multiple sclerosis, and other conditions. Drugs increase thyroid auto-antibodies.

Rifampin, used for tuberculosis;

Some drugs used for cancer chemotherapy.

Interferon.

Large doses of selenium, a common over-the-counter supplement.

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 2000 study suggested many elderly patients had 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.

In any case, elderly patients and 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 one-fifth of patients with the heart condition. About 40% of patients who have heart disease must take lower-than-average maintenance doses. The hormone has no effect and may even improve angina in the remaining four-fifths. It should be noted that 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. Newborns with congenital hypothyroidism should be treated with levothyroxine (T4) as soon as possible to prevent complications. Treating the infant after about a month and a half does not reverse any existing mental impairment, although it does reverse physical damage.

Single oral doses of levothyroxine (T4) can usually restore normal thyroid hormone levels within one to two weeks. Even with early treatment, evidence now suggests that mild problems in mental functioning persist into adulthood. Some experts urge treating newborns at slightly higher than recommended doses for the first two weeks, although more evidence is needed to determine the risks and benefits of this approach. Infants should be monitored closely to be sure that thyroxine levels are as consistently close to normal as possible. These children need to continue lifelong thyroid hormone treatments.

One study suggested that breast-fed babies with congenital hypothyroidism may test slightly better later on than bottle-fed infants. Soy-based infant formulas can reduce the intestinal absorption of thyroxine. If soy formula is introduced, the hormone dose should be increased, and when the formula is discontinued the thyroid dose should be reduced.

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 actually 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. Often, 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, then, the physician 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 were taking 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 where 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 now 150 micrograms for both men and women, with an upper limit of 1100 micrograms to avoid thyroid injury.

According to a 2000 study, when iodide-deficient children are given iodized salt, their mental status improves even if their iodide levels are still below normal. Another study reported that in areas where food supplies were low, iodine replacement caused an increase in the population's energy levels and fertility. (Unfortunately, this placed a higher burden on already low resources. Experts warn that while it is important to improve nutritional levels in developing countries, all concerns must be addressed.)

Although hypothyroidism from iodine deficiency is still very uncommon in nations where iodine has been added to salt, the consumption of iodized salt has declined in these countries over the past decades. In addition, iodine levels have been reduced in animal feed and bread products. Experts believe this may be causing an increase in subclinical hypothyroidism (without symptoms) even in developed countries.

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 three quarters of these patients. More research is needed.

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