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Thyroid Disorders and Diabetes

by Patricia Wu, MD

Thyroid disorders are very common in the general U.S. population, affecting up to 27 million Americans, although half that number remains undiagnosed. It is second only to diabetes as the most common condition to affect the endocrine system — a group of glands that secrete hormones that help regulate growth, reproduction, and nutrient use by cells. As a result, it is common for an individual to be affected by both thyroid disease and diabetes.

Since the thyroid gland plays a central role in the regulation of metabolism, abnormal thyroid function can have a major impact on the control of diabetes. In addition, untreated thyroid disorder can increase the risk of certain diabetic complications and can aggravate many diabetes symptoms. Luckily, abnormal thyroid function can easily be diagnosed by simple blood tests, and effective treatment is available. For all of these reasons, periodic screening for thyroid disorder should be considered in all people with diabetes.

What is the thyroid?
The thyroid is a butterfly-shaped gland located in the neck, just below the Adam’s apple and above the collarbone. It produces two hormones, thyroxine (T4) and triiodothyronine (T3), which enter the bloodstream and affect the metabolism of the heart, liver, muscles, and other organs. The thyroid gland operates as part of a feedback mechanism involving the hypothalamus, an area of the brain, and the pituitary gland, which is located within the brain.

First, the hypothalamus sends a signal to the pituitary through a hormone called TRH (thyrotropin-releasing hormone). When the pituitary gland receives this signal, it releases TSH (thyroid-stimulating hormone) to the thyroid gland. Upon receiving TSH, the thyroid responds by producing and releasing the two thyroid hormones (T3 and T4). The pituitary gland “monitors” the level of thyroid hormone in the blood and increases or decreases the amount of TSH released, which in turns regulates the amount of thyroid hormone produced.

Function of the thyroid
Thyroid hormone regulates the way the body uses energy. It works by attaching to specific proteins called receptors that are present in cells throughout the human body. Therefore, thyroid hormone exerts wide-ranging effects in regulating the function of virtually every organ. Consequently, any changes in the blood level of thyroid hormone can affect many body systems and cause a wide range of symptoms.

The extent to which each organ is affected varies widely between individuals, which is why thyroid dysfunction causes very different symptoms in different people. In general, the severity of symptoms of abnormal thyroid function depends on the severity of the actual condition, the length of time it has been present, and the person’s age. As a result, it is difficult to correctly diagnose thyroid disorder based only on symptoms. Fortunately, precise measurement of thyroid function is now possible with the TSH blood test, a test that directly measures the amount of TSH produced by the pituitary gland.

Common disorders of the thyroid
There are two basic disorders of the thyroid: hypothyroidism, or an underactive thyroid gland, and hyperthyroidism, or an overactive thyroid gland.

Hypothyroidism. The most common disorder of the thyroid is an underactive thyroid gland, or hypothyroidism. Some studies have shown that up to 10% of women and 3% of men in the United States have hypothyroidism and receive thyroxine replacement therapy. Although hypothyroidism can occur at any age and in either sex, it is most common in older women. It is estimated that up to 1 in 5 women over the age of 65 may have hypothyroidism. At the other end of the age range, 1 out of every 4,000 babies in the United States is born without a properly functioning thyroid (congenital hypothyroidism). (For more information about populations in which thyroid disorders are more likely, see “Who’s At Risk?”)

The symptoms and effects of hypothyroidism can vary greatly depending on the age and sex of the affected individual. The lack of thyroid hormone in an infant with untreated congenital hypothyroidism may cause cretinism, a condition resulting in severe growth delay and mental retardation. Routine screening for hypothyroidism in all newborns by a heel prick blood test has decreased the incidence of cretinism.

In older children, signs of hypothyroidism can include unexplained daytime fatigue, changes in school grades, difficulty concentrating, and inattentiveness in school. Sometimes, however, an unexplained change in growth rate is the only evidence of thyroid failure in children.

In women of reproductive age, hypothyroidism can impair fertility and increase the risk of miscarriage during the second trimester. Other symptoms may include a goiter (an enlarged thyroid gland), fatigue, weight gain, mood swings, depression, dry skin, brittle hair, fluid retention, muscle weakness, and constipation.

In the elderly, the symptoms can be very vague and are often mistaken for depression or dementia, since thyroid failure can cause sleep disturbance and poor memory.

Worldwide, the most common cause of hypothyroidism is dietary iodine deficiency. However, since iodine has been added to salt and other foods in the United States, hypothyrodism caused by iodine deficiency is very rare among Americans. The most common cause of hypothyroidism in the United States is an inherited autoimmune condition called Hashimoto thyroiditis, which affects up to 14 million people.

Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms begin to attack healthy tissue for unknown reasons. These natural defenses use proteins called antibodies. Hashimoto thyroiditis produces antibodies that damage the thyroid tissue, resulting in thyroid failure.

Other common causes of hypothyroidism include the surgical removal of the thyroid, exposure to radiation such as radioactive iodine therapy, or external radiation used to treat some forms of cancer. Certain drugs such as lithium carbonate (for treatment of bipolar disorder) and amiodarone (brand name Cordarone, a drug prescribed for certain heart conditions) can cause hypothyroidism. Rarely, abnormalities of the hypothalamus or pituitary gland may result in hypothyroidism.

Hyperthyroidism. Overactive thyroid, or hyperthyroidism, is less common than hypothyroidism. It tends to affect all age groups equally, but it is nine times more common in women. Like hypothyroidism, the symptoms of hyperthyroidism are varied and can be vague, particularly if the disease progresses slowly over a prolonged period. In children, it can result in accelerated growth, hyperactivity, loss of concentration, poor handwriting, and short-term memory loss. In young women, it may result in absent or irregular periods, recurrent miscarriages, and infertility.

In older women, hyperthyroidism can cause hot flashes, mood swings, sweating, and weight changes, symptoms that may be confused with signs of menopause. Other typical symptoms of hyperthyroidism include irritability, fast heart rate, weight loss despite increased appetite, frequent bowel movements, insomnia, decreased energy level, and shaky hands. In addition, a goiter may be present. (To learn more about symptoms of thyroid disorders, see “Symptoms and Signs.”)

The most common cause of hyperthyroidism in people under age 40 is Graves disease, a type of autoimmune thyroid disease. In this case, the antibodies stimulate the thyroid to enlarge and overproduce thyroid hormone. Some people with Graves disease develop eye problems that can cause the eyes to protrude and that may threaten vision. Other causes of hyperthyroidism include thyroid nodules, which are overactive (usually noncancerous) growths in an otherwise normal thyroid gland, and thyroiditis, or inflammation of the thyroid gland. (See “Suggested Reading” for more information about thyroid disorders.)

Thyroid disorder and diabetes
People with diabetes have an increased risk of developing thyroid disorder. In the general population, approximately 6% of people have some form of thyroid disorder. However, the prevalence of thyroid disorder increases to over 10% in people with diabetes.
Since people with one form of autoimmune disorder have an increased chance of developing other autoimmune disorders, people with Type 1 diabetes have a higher risk of autoimmune thyroid disorder. Up to 30% of women with Type 1 diabetes have some form of autoimmune thyroid disease. Postpartum thyroiditis, a form of autoimmune thyroid disease that causes thyroid dysfunction within a few months after delivery of a child, is three times more common in women with diabetes.

Although Type 2 diabetes is not an autoimmune disorder, there have been many reports showing a higher occurrence of thyroid diseases, particularly hypothyroidism, among people with Type 2 diabetes. The association between Type 2 diabetes and thyroid disorder, however, remains unexplained.

Effect on diabetes control
Since normal thyroid function is essential to regulate energy metabolism, abnormal thyroid function may have profound effects on blood glucose control in diabetes. Both hyperthyroidism and hypothyroidism can affect the course of diabetes, but their effects are somewhat different.

Hyperthyroidism. Hyperthyroidism is typically associated with worsening blood glucose control and increased insulin requirements. The excessive thyroid hormone causes increased glucose production in the liver, rapid absorption of glucose through the intestines, and increased insulin resistance (a condition in which the body does not use insulin efficiently). It may be important to consider underlying thyroid disorder if a person has unexplained weight loss, deterioration in blood glucose control, or increased insulin requirements. Sometimes hyperthyroidism may even unmask latent diabetes.

Having diabetes increases a person’s risk for heart disease, and many people with diabetes have a heart condition such as coronary heart disease or heart failure. Since hyperthyroidism causes rapid heart rate and increases the risk of abnormal heart rhythm, it may also bring on angina (chest pain), worsen heart failure or interfere with the treatment of heart failure, as well as further increase the risk of other heart problems.

Prolonged, untreated hyperthyroidism can cause excessive bone loss, leading to osteoporosis, or bone thinning. Osteoporosis raises the risk of bone fractures, making falling much more dangerous. People with diabetes who have peripheral neuropathy are at an increased risk for falls due to poor foot sensation and sometimes loss of proprioception, or loss of the stimuli that tell the brain where a body part is in space, in relation to other objects. Therefore, the combination of hyperthyroidism and diabetes, particularly when neuropathy is present, increases the risk of fractures that may result in disability, especially in the elderly.

Hypothyroidism. Hypothyroidism rarely causes significant changes in blood glucose control, although it can reduce the clearance of insulin from the bloodstream, so the dose of insulin may be reduced. More important, hypothyroidism is accompanied by a variety of abnormalities in blood lipid levels. This includes increased total cholesterol and LDL (low-density lipoprotein or “bad”) cholesterol levels, and increased triglyceride levels. The abnormal lipid pattern typical of Type 2 diabetes (low HDL, or “good” cholesterol; high triglycerides; and a high proportion of small, dense LDL particles) is usually worsened by hypothyroidism. These changes further raise the already high risk of cardiovascular diseases such as heart disease and stroke among people with diabetes.

Pregnancy, diabetes, and thyroid disorder
Pregnancy-related thyroid dysfunction is three times more common in women with diabetes and should be anticipated in every pregnant woman with Type 1 diabetes. Postpartum thyroiditis may cause fluctuating thyroid hormone levels in the months following delivery. In addition to symptoms such as fatigue, depression (the “baby blues”), irritability, and heart palpitations, blood glucose control and insulin requirements may be affected during this period of thyroid dysfunction and profound reproductive hormonal changes. Continued monitoring of thyroid function is necessary in all women who experience postpartum thyroiditis, since roughly one-third will develop permanent hypothyroidism within three to four years and will require thyroxine replacement.

Women who have diagnosed hypothyroidism and already take thyroxine before pregnancy often need to increase the dose of thyroxine during pregnancy. Adequate thyroxine replacement is vital for the baby’s neurological development. Women with active Graves disease may enter a period of remission during pregnancy, when the disease becomes less active, but they can expect a recurrence following delivery.

If hyperthyroidism is poorly controlled during pregnancy, the risk of maternal complications such as preeclampsia (a serious condition characterized by high blood pressure) and fetal problems such as prematurity increases. The maintenance of normal thyroid function and tight blood glucose control is therefore of utmost importance during pregnancy to ensure a successful outcome.

Diagnosis of thyroid disorder
As mentioned earlier, the diagnosis of abnormal thyroid function based solely on symptoms can be difficult. In people with diabetes, it may be even more difficult because of the complex interrelationships of thyroid function and diabetes. Both chronically high blood glucose and hyperthyroidism can cause weight loss despite good appetite, weakness, and fatigue. Likewise, severe diabetic kidney disease can produce symptoms such as swelling, weight gain, and hypertension, which may be confused with hypothyroidism.

The most reliable method used to diagnose thyroid disease is the simple, relatively inexpensive, yet highly sensitive TSH blood test. This test measures directly the amount of TSH produced by the pituitary gland. Since the pituitary is the first organ to recognize abnormal thyroid function, testing its function is the most sensitive way to monitor thyroid function. In addition to diagnosis, the TSH test is also used to monitor and adjust the dosage of thyroxine therapy.

Before the introduction of the TSH test in the late 1960’s, blood tests for thyroid function measured only the levels of the thyroid hormones, T3 and T4. However, these hormone levels can appear relatively normal even when the thyroid is not functioning normally, because the pituitary gland will compensate for thyroid dysfunction. When the thyroid starts to fail (a sign of early hypothyroidism), the pituitary responds by producing higher levels of TSH to stimulate the thyroid to produce more thyroid hormones, thereby maintaining normal circulating T3 and T4 levels. Conversely, when the thyroid gland produces too much thyroid hormone (a sign of early hyperthyroidism), the pituitary responds by producing less TSH, thereby reducing T3 and T4 production from the thyroid.

Therefore, prior to any changes in the thyroid hormone levels, there is a detectable change in the TSH level, which indicates abnormal thyroid function. A normal TSH level ranges from 0.4 mU/ml to 4.0 mU/ml (microunits per milliliter). A below-normal TSH level indicates hyperthyroidism, and an above-normal TSH level indicates hypothyroidism.

An elevated TSH level accompanied by normal thyroid hormone levels is known as subclinical hypothyroidism. People with subclinical hypothyroidism often do not have any symptoms. However, they do face the increased risks of cardiovascular disease associated with hypothyroidism, due to the abnormalities in blood lipid levels. Some doctors have even suggested that a TSH level in the upper-normal range (2.5–4.0 mU/ml) should be considered as evolving thyroid failure.

Thyroid antibodies that are produced in autoimmune thyroid diseases can also be measured by blood testing. The presence of these antibodies can help determine the underlying cause of thyroid disorder. The most specific antibody test is called the anti-TPO antibody test.

Treatment of thyroid disease
Nearly all thyroid diseases are treatable. Hypothyroidism and hyperthyroidism often require long-term or lifelong treatment, depending on the specifics of the diagnosis.

Hypothyroidism. The treatment for hypothyroidism is to replace the missing thyroid hormone. The most common form of thyroid hormone is a synthetic derivative, levothyroxine, which is usually taken as one pill daily. This is a simple yet very effective treatment of hypothyroidism. Once the treatment is started, TSH testing every two or three months is necessary to adjust to the correct dose. When a stable dose is achieved, annual TSH testing is generally adequate for monitoring purposes.

The symptoms of hypothyroidism may take several months of therapy to resolve. Often, lifelong treatment is necessary. Natural thyroid extract derived from animal sources is a less commonly used form of thyroid replacement and has the disadvantage of inconsistent dosage that varies from one batch of pills to another.

Certain supplements, including iron supplements, calcium supplements, and multivitamins that contain iron or calcium, can interfere with the absorption of thyroxine. For this reason, these pills should be taken at least two hours apart from thyroxine. In addition, it’s a good idea to let your physician know of any supplements or other medicines you take in addition to levothyroxine.

Hyperthyroidism. There are several options for treatment of hyperthyroidism, with the choice dependent on the cause of the disorder; it must be individually determined. Long-term oral antithyroid medicines such as methimazole (Tapazole) and propylthiouracil (PTU) are effective in controlling the production of thyroid hormone. Regular blood test monitoring is necessary throughout the course of treatment.

Radioactive iodine therapy is the most common treatment used in the United States for hyperthyroidism. It has a very high cure rate but often results in permanent hypothyroidism. Surgery offers an alternative, particularly in people with very large goiters. All these treatments are effective in controlling or curing hyperthyroidism.

Importance of screening
Abnormal thyroid function can have a major impact on diabetes control and increase a person’s risk of developing diabetic complications. Because of the complications that can result from untreated thyroid disorder, regular screening is recommended to allow early detection and treatment. For people with Type 1 diabetes, annual screening is advisable. For people with Type 2 diabetes, screening should be done at the time of diagnosis and then repeated every five years thereafter. The frequency of screening should increase with advancing age, since the incidence of thyroid disorder increases with age. For people over the age of 60, annual screening is recommended.

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Also in this article:
Suggested Reading
Symptoms and Signs
Who's At Risk?

 

 

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