How is Hypothyroidism Treated?

September 1998
A review of the current standard treatment options for low thyroid function.

In the nineteenth century, a few years after a relationship was observed between myxedema and surgical removal of the thyroid gland, physicians began to feed hypothyroid patients whole or powdered extracts of animal thyroid glands. This was one of the first successful medical treatments based on careful scientific observation. Thyroid hormone pills are now the standard treatments, but the therapeutic principle is the same as it was 100 years ago -- to provide the body with replacement thyroid hormone when the gland is not able to produce enough itself. Sensitive tests now diagnose hypothyroidism at earlier stages -- when TSH levels are high but thyroxine levels are normal. Some physicians are uncertain about whether to treat such cases of subclinical hypothyroidism. One guide for treatment are the patient's own feelings. Some people have few symptoms at high TSH levels; others feel unwell and fatigued at low levels. Between 25% and 50% of patients with subclinical hypothyroidism feel better after taking thyroid medication, even if they do not report any symptoms. Some experts believe that the association between hypothyroidism and unhealthy cholesterol and other lipid levels warrants treatment for subclinical hypothyroidism. Others feel there is no downside in delaying treatment until after symptoms develop.

Levothyroxine

The current treatment of choice is levothyroxine (Synthroid, Levothroid, Levoxyl, LEVO-T). This drug is a synthetic derivative of T4 (thyroxine), and it normalizes blood levels of TSH, T4, and T3. A recent study reported that low-cost generic thyroid preparations are as effective as and certainly less expensive than the brand name drugs Synthroid and Levoxyl. The manufacturer of Synthroid, who had expected the results to favor its drug, had been accused of blocking this study from publication for at least two years. The manufacturer claims the study was flawed, but experts reviewing it found the study to be well-conducted. Levothroid, the other major brand, does not appear to have significant differences from the other branded and generic drugs.

Initial dosage levels are determined on an individual basis. Some patients can begin by taking full replacement doses of thyroid hormones; others need to build up gradually. In uncomplicated cases, generally the initial dose is 50 micrograms per day, with doses increased at 3 to 4 week intervals until it reaches between 100 and 150 micrograms. Few patients with hypothyroidism ever require more than this, although pregnant women may require higher than normal doses. Elderly patients and those with heart conditions usually start with lower doses, since a large initial dose may be a shock to the heart; about 40% of patients who have both hypothyroidism and angina cannot tolerate full replacement of thyroid hormone. On the other hand, young adults with a short history of hypothyroidism might take a full initial dose. A recent study indicated that some patients may be able to maintain normal thyroid levels by taking one large weekly dose, rather than small daily ones, which could help compliance.

One small study suggested that large amounts of dietary fiber may reduce the action of levothyroxine; people whose diets are very high in fiber may require larger doses of the drug. Levothyroxine is slowly assimilated by body organs, and it usually takes three to six weeks of treatment for an improvement in symptoms in adults.

Patients start feeling better two to three weeks after beginning treatment. Usually they experience weight loss, less puffiness, and improved pulse rate early on; improvements in anemia and skin, hair, and voice tone, however, may take a few months. Other conditions, such as goiter and high LDL cholesterol levels decline more gradually. (HDL -- the so-called good cholesterol -- levels are not affected by treatment.) Once the proper dose has been established to normalize thyroid blood levels, patients usually see their physicians once a year for a brief evaluation. Thyroid failure is an ongoing process, usually due to chronic inflammation of the gland. A dose of thyroid medication that is appropriate for a patient 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. If thyroid levels are normal and patients continue to complain of lack of energy, the physician should investigate other factors that might be responsible.

Establishing a habit of taking the medication at the same time may help prevent missed doses, although 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. Levothyroxine can be taken at any time of day either with or without food. It is identical to the thyroxine the body manufactures, so side effects are nearly unheard of. The only problems encountered with this medication is under- or overdosing.

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. Sluggishness, mental dullness, feeling cold, or muscle cramps may persist. Even mild hypothyroidism without any symptoms can lead to an increase in cholesterol levels. 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.

Effects of Overdosing: Thyrotoxicosis

Overdosing can cause thyrotoxicosis -- the symptoms of hyperthyroidism. These include a rapid heart beat, palpitations, wide variations in pulse, angina, tremor, nervousness, insomnia, headache, a change in appetite, diarrhea, weight loss, excessive sweating, an intolerance to heat, fever, and muscle pain. A patient with too much thyroid hormone in the blood is at an increased risk for abnormal heart rhythms, rapid heartbeat, 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.

Effects of Suppressive Thyroid Therapy

Suppressive thyroid therapy is thyroid treatment that is high enough to block the production of natural TSH but too low to cause hyperthyroid symptoms. Often patients being given suppressive treatment have thyroid cancer or need to have thyroid nodules reduced. Studies have shown that postmenopausal women taking suppressive thyroid therapy are at risk for accelerated osteoporosis, a disease that reduces bone mass and increases risk of fractures. In most cases, bone density loss can be reduced or avoided by taking no higher a dose of thyroxine than necessary to restore normal thyroid function. Some researchers have found that although bone loss occurs with suppressive therapy, the danger for fracture is low. They believe that the cholesterol-lowering benefits of suppressive therapy outweigh the small risk for fractures. Estrogen replacement therapy, in any case, can help negate the risk of thyroid-induced osteoporosis as well as protect against heart disease in older women. It does not appear that premenopausal women or men taking suppressive therapy have the same risk for osteoporosis, more research needs to be done on these groups.

Effects of Long-Term Treatment

Patients with Hashimoto's thyroiditis who have symptoms of hypothyroidism or large goiters usually receive life-long levothyroxine therapy. Such patients without symptoms should be monitored regularly for signs of hypothyroidism. Although studies indicate that postmenopausal women who are taking long-term normal replacement thyroxine have no out-of-the-ordinary risk for osteoporosis, such women should consider estrogen replacement therapy if they have no contraindications to it.

Interactions with Other Medications

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.

Other Thyroid Medications

Liothyronine (Cytomel, Triostat) is synthetic T3; this drug is not ordinarily prescribed except in special circumstances, because of its unpredictability.

Desiccated or dried powdered thyroid (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 recommended. Desiccated thyroid has no advantage over synthetic thyroxine hormone, and because it comes from a natural source, the potency may vary from one batch to another.

Treatment for Newborns and Infants with Hypothyroidism

Newborns with congenital hypothyroid should be treated as soon as possible to prevent mental deficiency, poor growth, and abnormal development. These children should be monitored closely to be sure that thyroxine levels are as consistently close to normal as possible. Single oral doses of levothyroxine can usually restore normal thyroid hormone levels within one to two weeks. Treatment after about a month and a half of age does not reverse any existing mental impairment, but it does reverse physical damage. These children need to continue life-long 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 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 by up to 50%. In very rare cases, women may develop hypothyroidism during pregnancy 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, it is usually mild and thyroid levels most often return to normal over time. If symptoms, such as depression, are severe, however, women can take thyroid replacement until the condition resolves.

Treatment for Myxedema Coma

Myxedema coma is an emergency situation and the patient should be given intravenous doses of thyroid hormone; in this case liothyronine -- synthetic T3 -- is preferable to levothyroxine. Any other critical accompanying conditions, including low body temperature, slow heart rate, low blood sugar and any difficulty in breathing, should also be treated.

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 the patient is usually treated with cortisone acetate, a stress hormone, before thyroid replacement starts.

Inappropriate Indications

In one study of those taking thyroid hormone, 12% of women and 29% of men were taking it inappropriately. Women with menstrual problems and repeated miscarriages, and men with low sperm counts have been treated with thyroid hormones. 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 and use of thyroid hormones can weaken muscles and over the long term, even heart muscles.

Well-Connected Board of Editors

Harvey Simon, M.D., Editor-in-Chief
Massachusetts Institute of Technology; Physician, Massachusetts General Hospital

Masha J. Etkin, M.D., Gynecology
Harvard Medical School; Physician, Massachusetts General Hospital

John E. Godine, M.D., Ph.D., Metabolism
Harvard Medical School; Associate Physician, Massachusetts General Hospital

Daniel Heller, M.D., Pediatrics
Harvard Medical School; Associate Pediatrician, Massachusetts General Hospital; Active Staff, Children's Hospital

Irene Kuter, M.D., D. Phil., Oncology
Harvard Medical School; Assistant Physician, Massachusetts General Hospital

Paul C. Shellito, M.D., Surgery
Harvard Medical School; Associate Visiting Surgeon, Massachusetts General Hospital

Theodore A. Stern, M.D., Psychiatry
Harvard Medical School; Psychiatrist and Chief, Psychiatric Consultation Service, Massachusetts General Hospital

Carol Peckham, Editorial Director

Cynthia Chevins, Publisher

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