Hyperthyroidism is a condition in which the thyroid gland over-produces the hormones that regulate the body's metabolism. The excess thyroid hormones cause many symptoms. While hyperthyroidism responds well to treatment, there may be complications, and recurrence is common Figure 01. The thyroid is a hormone-secreting gland located in the neck that produces two important hormones: thyroxine and triiodothyronine. These hormones promote normal growth and development, and help to control the body's metabolism.
Normally, the production of thyroxine and triiodothyronine is regulated by the pituitary gland. When blood levels of thyroid hormones are low, the pituitary increases production of thyrotropin, which is also known as thyroid-stimulating hormone (TSH). TSH in turn stimulates the thyroid to secrete thyroxine and triiodothyronine. Conversely, high blood levels of thyroid hormones signal the pituitary to turn off production of TSH, which in turn stops production of the thyroid hormones. This “feedback loop” controls the levels of thyroid hormones in the blood.
Figure 01. Glands of the endocrine system
Graves' disease, in which the whole gland becomes overactive, is the most common type of hyperthyroidism. Approximately 70% to 90% of people with hyperthyroidism have Graves' disease. In the disorder, the entire thyroid gland becomes enlarged and overactive. The enlarged gland appears as a bulge in the neck (goiter). The generalized overactivity of the thyroid in Graves' disease distinguishes it from another type of hyperthyroidism in which one or more lumps (nodules) in the thyroid become overactive, a condition called toxic nodule, or multinodular goiter. Graves' disease is approximately four times more common in women than men; the reason for this difference is not well understood.
Hyperthyroidism occurs in about 0.5% of the population, and is more common in women than in men. The incidence of hypothyroidism increases with age. Only 5% of hyperthyroid patients are diagnosed before age 15, and the condition is most frequently identified in people between the ages of 30 and 40.
Hyperthyroidism is a condition that occurs when the body produces too much thyroid hormone Table 01. Overstimulation of the thyroid may be caused by several different factors, acting at the thyroid itself (as is the case with Graves' disease and multinodular goiter), or less commonly, at the pituitary gland (as is the case in one type of pituitary tumor). The pituitary produces excess TSH, which in turn causes the thyroid to produce excess amounts of thyroid hormones.
Table 1. Causes of Hyperthyroidism
Graves' disease (autoimmune stimulation of the thyroid gland) Hyperactivity of solitary or multiple thyroid nodules Inflammation of the thyroid gland (e.g., associated with infection or pregnancy) Intake of excessive amounts of thyroid hormones Excessive production of thyroid-stimulating hormone (TSH) by the pituitary gland
Adapted from Hershman JM, Thyroid Dysfunction, Current Practice of Medicine 1999; 2(10).
Graves' disease is a disorder in which antibodies stimulate the thyroid gland. A specific type of antibody is found in the blood of people with Graves' disease. This antibody stimulates the entire thyroid gland to grow and produce excess amounts of thyroid hormone. This type of hyperthyroidism tends to run in families, but little is known about the way it is inherited, or about other specific causes of the disease. Although the direct cause of Graves' disease is specific antibodies circulating in the blood, physicians have long thought that the condition may be triggered by severe emotional stress, such as the loss of a loved one. Studies have shown that stress can affect the ability of the immune system to function, so such a link is certainly possible. However, many patients develop Graves' disease without having identifiable stress in their lives.
Hyperthyroidism may be caused by overactivity of solitary or multiple benign nodules within the thyroid. Individual or multiple nodules within the thyroid may enlarge and begin producing excess amounts of thyroid hormone. These nodules produce hormones, even in the absence of TSH, and as such are not affected by the normal mechanisms that control thyroid hormone levels.
Some women experience hyperthyroidism after giving birth. For reasons not well understood, some women experience postpartum inflammation of the thyroid (thyroiditis). This inflammation appears to be caused by antibodies that attack the thyroid and cause a leakage of thyroid hormone into the blood. Although an estimated 5% to 7% of women will develop the condition after giving birth, it frequently goes undiagnosed, perhaps because the symptoms are attributed to the normal recovery process after childbirth.
Because thyroid hormones affect almost every tissue in the body, a wide range of symptoms may occur with hyperthyroidism Table 02. Thyroid hormones increase the body's metabolic rate, speeding up the body's functions in much the same way as a strong stimulant would. The resulting symptoms include nervousness, irritability, increased perspiration, thinning of the skin, brittle hair, muscular weakness, tremors, heart palpitations, rapid heartbeat, frequent bowel movements, weight loss, and changes in menstrual flow.
Heart problems, especially palpitations, rapid heartbeat, or abnormal heart rhythms, occur most frequently in older adults. These older patients may also become weak, sleepy, confused, or depressed.
Table 2. Symptoms of Hyperthyroidism
General symptoms Nervousness and irritability Heart palpitations or rapid heartbeat Difficulty breathing Changes in menstrual flow Changes in heat tolerance or sweating Impair fertility Tremors Weight loss Mental disturbances Sleep disturbances Changes in appetite Frequent bowel movements Fatigue and muscle weakness Thyroid enlargement Sudden paralysis Symptoms specific to Graves' disease Changes in vision or tolerance to light Eye irritation Double vision Bulging or protruding eyes Swelling or thickening of the skin in front of the shins.
*Adapted from the ACCE Clinical Practice Guidelines for the Evaluation and Treatment of Hyperthyroidism and Hypothyroidism. Endocrine Practice 1995; 1(1)
In addition to other symptoms of hyperthyroidism, patients with Graves' disease sometimes experience inflammation of tissues around the eyes. In Graves' disease, the eyes may appear to be enlarged because the upper eyelid becomes elevated. Less frequently, the eyes may bulge from their sockets because of tissue inflammation behind the eyeball. Inflammation affecting the muscles that control eye movement may prevent the eyes from moving properly, resulting in double vision. The cause of these symptoms is unknown, and their severity is not determined by the amount of excess thyroid hormone produced by the body. Serious or permanent damage to the eyes, however, occurs only rarely.
A very small percentage of the people with Graves' disease also develop a lumpy, itchy reddish thickening of the skin in front of their shins. The cause of this symptom and the reason why it is limited to so few patients with Graves' disease is unknown.
The symptoms of hyperthyroidism generally develop over time. In most cases, thyroid hormone production increases gradually over time. At first, the symptoms may be mild and attributed to stress, anxiety, or other normal life events. As the thyroid hormone production accelerates, however, the symptoms become more pronounced. In Graves' disease, changes in the eyes sometimes appear before other symptoms.
Although the genetic basis is not well understood, inheritance plays some role in development of Graves' disease.
Hyperthyroidism occurs frequently in older adults. In many cases, hyperthyroidism in older adults has few prominent symptoms. The enlarged thyroid and nervousness or heat intolerance commonly reported by younger patients are often missing. Weight loss and weakness may be attributed to age or other conditions. As a result, hyperthyroidism may be overlooked. Many physicians now recommend regular screening with a blood test to identify hyperthyroidism in older adults.
Smoking increases the possibility that Graves' disease will involve the eyes. Therefore, if you smoke, quit.
During the initial visit, the doctor will start with a medical history and ask about changes in physical health and whether there is a family history of thyroid disease. When hyperthyroidism is suspected, the physician will ask about nervousness, fatigue, heart palpitations, difficulty breathing, weight loss, heat intolerance, irritability, shaking (tremors), weakness, decreased menstrual flow (in women), difficulty sleeping, increased perspiration, increased frequency of bowel movements, changes in appetite, and any noticeable enlargement of the neck. If the physician suspects Graves' disease, he or she will also ask about changes in vision, eye irritation, and possible intolerance to bright light. The physician will also ask questions to determine any family history of thyroid disease.
In order to identify non-Graves' disease hyperthyroidism, the physician will ask about iodine exposure, any thyroid hormone use, and any recent pregnancy or childbirth.
Finally, because thyroid hormone blood tests may be affected by certain medications, the physician will determine whether any medication is currently being taken.
The doctor will then perform a comprehensive physical examination, which includes an examination of the thyroid, eyes, skin, heart, and muscles. The physician will examine the thyroid for generalized or nodular enlargement, the eyes for symptoms of inflammation, the heart for pulse, blood pressure, and heart rhythm, the muscles for evidence of weakness, and the skin on the shins for evidence of thickening or inflammation. In addition, the patient's weight will be recorded as a baseline for future changes.
The doctor will order blood tests and possibly a thyroid scan to make a definitive diagnosis. Elevated blood levels of thyroid hormones are the hallmark of hyperthyroidism. In most cases, levels of the pituitary hormone TSH will be lower than normal. This is because TSH is secreted from the pituitary gland in order to stimulate the thyroid to produce thyroid hormone. If the thyroid is producing too much thyroid hormone, the pituitary will stop secreting TSH. In contrast, elevated blood levels of TSH may indicate the presence of a tumor in the pituitary gland.
Depending on the results of the blood test, the doctor may order a thyroid scan. In this test, the patient swallows a solution containing radioactive iodine, and the thyroid is scanned to determine the pattern and extent of the uptake. This test is usually performed to distinguish between Graves' disease and inflammation of the thyroid. If the patient has Graves' disease, the radioactive iodine will be taken up more or less uniformly by the entire gland. In the infrequent instances where the thyroid is inflamed, it will take up relatively little radioactive iodine.
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