Thyroid Disease and HCV
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Thyroid disorders are among the many conditions that may occur in people with chronic hepatitis C. Various studies indicate that somewhere between 2% and 20% of people with HCV will develop thyroid problems. While thyroid dysfunction can be caused by interferon therapy, research shows that it is also associated with HCV itself. Fortunately, thyroid problems are readily treatable.
The Thyroid Gland
The thyroid is a butterfly-shaped endocrine gland located in the neck below the larynx (voice box). It produces hormones that regulate metabolism, affecting many bodily systems. The thyroid gland is stimulated to produce its own hormones by another hormone—thyroid-stimulating hormone, or TSH—released by the pituitary, the “master gland,” in the brain. In response to TSH, the thyroid takes up iodine from food and uses it to produce the hormones T3 and T4 (thyroxine), which are then released into the bloodstream. In a complex feedback loop, levels of thyroid hormones in the blood influence how much TSH is released, while the production of TSH is in turn regulated by thyrotropin-releasing hormone (TRH) secreted by the hypothalamus, another gland in the brain.
There are several different conditions related to the thyroid, including:
Hypothyroidism: an underactive thyroid, or insufficient production of thyroid hormones, leading to decreased metabolic activity. Symptoms may include fatigue, sensitivity to cold, constipation, muscle weakness, depression, weight gain, and heavy menstruation in women. The condition usually progresses over time and may lead to coma and death.
Hashimoto’s disease (autoimmune thyroiditis): the most common type of hyperthyroidism, caused by the immune system attacking the thyroid tissue.
Hyperthyroidism: an overactive thyroid, or excessive production of thyroid hormones, leading to increased metabolic activity. Symptoms may include insomnia, feeling warm, increased sweating, frequent bowel movements or diarrhea, rapid heart rate, heart palpitations, high blood pressure, tremors, anxiety, increased appetite, weight loss, and decreased menstrual flow in women.
Grave’s disease: the most common type of hyperthyroidism, caused by an autoimmune reaction in which antibodies bind to TSH receptors and cause the thyroid to produce excessive hormones. Symptoms are the same as those listed above, plus bulging of the eyes and thickening of the skin on the lower legs.
Thyroiditis: inflammation of the thyroid gland, which may cause increased or decreased hormone production.
Goiter: an enlarged thyroid gland, which may be associated with either hyperthyroidism or hypothyroidism. If severe, the oversized gland may press on structures in neck, leading to difficult breathing or swallowing.
Thyroid cancer: malignant tumors or growths in the thyroid.
Hypothyroidism and hyperthyroidism may be mild or severe. They may be asymptomatic, or symptoms may be so subtle that people don’t realize they have a problem. In addition, some of the symptoms—such as fatigue and depression—mimic those associated with HCV or its treatment.
What Causes Thyroid Problems?
While various factors can cause thyroid problems, one of the most common is autoimmune disease in which the immune system attacks the body. Normally the immune system can recognize the body’s own tissues, but when this process goes awry, B cells may produce antibodies that target parts of the body, or T-cells may mistake bodily cells for foreign invaders. Researchers do not know what causes the immune system to run amok, but heredity and sex hormones clearly play a role. Women are much more likely than men to develop autoimmune conditions; Grave's disease is about seven times more common in women, and the risk of Hashimoto’s disease many be as much as fifty times higher.
Viruses, too, may trigger autoimmunity, which may help explain why autoimmune conditions are common in people with HCV. Chronic hepatitis C is associated with several types of autoimmune disease including cryoglobulinemia and rheumatoid arthritis, as well as thyroid disorders (see June 2002 HCV Advocate). As described above, autoimmune reactions can cause either hypothyroidism (Hashimoto’s disease) or hyperthyroidism (Grave’s disease).
Many studies have shown that interferon therapy can cause autoimmune thyroid conditions or worsen existing thyroid disease (either hypothyroidism or hyperthyroidism). This is thought to occur because interferon stimulates immune system activity. Research shows that thyroid problems occur in about 5-15% of people taking interferon (often several months into treatment) and that levels of anti-thyroid antibodies may rise. Treatment-related thyroid disorders are seen more often in women than in men, and are more common in people with pre-existing thyroid problems or high levels of anti-thyroid antibodies. Usually thyroid dysfunction resolves when interferon is discontinued, but it is sometimes permanent (chronic autoimmune thyroiditis). In some cases, thyroid problems develop after interferon is stopped.
Although interferon therapy is a common cause of thyroid problems in people with hepatitis C, research indicates that HCV itself can trigger thyroid disorders. Several studies have shown that thyroid dysfunction is more prevalent in HCV positive people than in HCV negative people, even among those not receiving treatment. Dr. Luisa Fernandez-Soto and colleagues compared patients being treated with interferon for hepatitis B or C; they found that anti-thyroid antibodies were about four times more common in people with HCV than in those with HBV, and at the end of treatment people with HCV were four times more likely to have thyroid dysfunction. However, because some HBV patients being treated with interferon do develop thyroid problems, HCV can’t be given all the blame. Importantly, HIV infection is also associated with thyroid disorders, so HCV/HIV coinfected people may be at even greater risk.
Diagnosis and Management
Hypothyroidism and hyperthyroidism are diagnosed using tests that measure levels of TSH and thyroid hormones in the blood. Typically, a low TSH level indicates that the thyroid is overactive, while a high level points to an underactive thyroid. These tests are important because thyroid dysfunction is so often asymptomatic. Other tests measure the level of anti-thyroid antibodies in the blood.
Before starting interferon, all people with HCV should have their levels of TSH and thyroid hormones measured, both to establish a baseline and to detect subclinical thyroid dysfunction. Tests of anti-thyroid antibodies can help predict whether thyroid problems will occur during treatment; most studies show that people with higher antibody levels are more likely to develop autoimmune thyroid disease. Once interferon therapy is started, thyroid function should be monitored regularly, about once per month. Some doctors also recommend that thyroid tests should be done periodically even after treatment is completed.
Hypothyroidism and hyperthyroidism can both be treated. If the thyroid does not produce enough hormones, people can take a synthetic version of T4 called levothyroxine (L-thyroxine), usually one pill per day. Some trial and error may be required over a few weeks or months to determine the proper dose. Treatment may be temporary (for example, if a person has interferon-related thyroid dysfunction) or may be lifelong.
Treatment of hyperthyroidism is more complex. There are anti-thyroid drugs that decrease the production of thyroid hormones (e.g., methimazole [Tapazole], propylthiouracil). But for long-term management, usually people are treated with radioactive iodine (which kills thyroid cells and causes the gland to shrink) or, less commonly, surgery to remove all or part of the thyroid (thyroidectomy). With either of these procedures, it often happens that the thyroid then becomes underactive, necessitating subsequent treatment with L-thyroxine.
Although thyroid disorders are a concern for people with hepatitis C—especially those taking interferon—it is important to remember that most people with HCV do not experience thyroid dysfunction. And with conscientious monitoring and proper treatment, hypothyroidism and hyperthyroidism are easily managed. To ensure that you get appropriate treatment, be sure to tell your doctor if you have any symptoms that may suggest a thyroid problem.
Carella, C. and others. Longitudinal study of antibodies against thyroid in patients undergoing interferon-a therapy for HCV chronic hepatitis. Hormone Research 44:110-4. 1995.
Deutsch, M. and others. Thyroid abnormalities in chronic viral hepatitis and their relationship to interferon alfa therapy. Hepatology 26(1):206-10. 1997.
Fernandez-Soto, L. and others. Increased risk of autoimmune thyroid disease in hepatitis C vs hepatitis B before, during, and after discontinuing interferon therapy. Archives of Internal Medicine 158(13):1445-8. 1998.
Tran, A. and others. Hepatitis C virus and Hashimoto’s thyroiditis. European Journal of Medicine 1:116-8. 1992.
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