Hyperthyroidism

1. Excessive functional activity of the thyroid gland.
2. The abnormal condition resulting from
hyperthyroidism marked by increased metabolic rate, enlargement of the thyroid gland, rapid heart rate, high blood pressure and various secondary symptoms.

Hypothyroidism

A deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold and menstrual
disturbances. If untreated, it progresses to full blown myxedema. In juveniles, the
manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is
called secondary hypothyroidism.

Autoimmune Thyroiditis

A progressive disease of the thyroid gland with antibodies in the blood stream directed against the thyroid and infiltration of the gland by lymphocytes (a key type of white blood cells involved in the immune response). This immune response is against one's own thyroid. (it is
autoimmune.) predominantly affects women.  Can be familial. Also called hashimoto's disease or Hashimoto's Thyroiditis.

Broussolle C, Steineur MP, Bailly F, Zoulim F, Trepo C Service de medecine interne, Hotel-Dieu, Lyon, France. INTRODUCTION:

The combination of hepatitis C virus (HCV) infection and thyroid diseases raises several issues that are the prevalence of thyroid autoimmunity in patients with chronic hepatitis C, the prevalence of HCV infection in patients with autoimmune thyroid diseases, and the effects of interferon alpha treatment on thyroid function in chronic HCV hepatitis. CURRENT KNOWLEDGE AND KEY POINTS: The prevalence of anti-thyroid auto-antibodies ranges from 4.6 to 15% in HCV infection, which is considered as significant by various authors. Results have to be interpreted according to the following: the type of auto-antibodies detected, the age, sex, ethnic origin of the population studied, and characteristics of the control population. Recent data are suggestive of a high prevalence of anti-thyroid auto-antibodies in females with HCV infection. An increased prevalence of HCV infection in patients with Hashimoto's thyroiditis is not confirmed. During treatment of chronic hepatitis C, interferon alpha induces thyroid dysfunctions (3 to 15% of the cases) with various clinical presentations. Hypothyroidism is more common (two out of three cases) than hyperthyroidism (one out of three cases). Hyperthyroidism followed by hypothyroidism has also been described. Clinical symptoms vary, ranging from subclinical to severe manifestations. Thyroid dysfunction may be delayed after discontinuation of the interferon treatment. Hypothyroidism is easily cured by L-thyroxine replacement therapy when necessary, and regression may be observed following discontinuation of interferon treatment. Each case of hyperthyroidism has to be precisely evaluated. Development of anti-thyroid antibodies or an increase in anti-thyroid antibodies titers is often observed during interferon alpha treatment, thus suggesting the existence of immunological mechanisms at the origin of thyroid dysfunction. Furthermore, interferon would directly act on iodine. FUTURE PROSPECTS AND PROJECTS: Clinical studies are still necessary to better clarify the links between HCV infection and thyroid autoimmunity, and to determine risk factors for the development of thyroid dysfunction during interferon alpha therapy. The effects of HCV and interferon alpha on thyroid autoimmunity and function have to be investigated in basic research. PMID: 10522298, UI: 99451796

Thyroid Disorders in Chronic Hepatitis C

The objective of the current study was to explore the association of hepatitis C virus (HCV) infection with thyroid disorders. Italian researchers investigated the prevalence of thyroid disorders in 630 consecutive patients with chronic hepatitis due to HCV infection.

All patients were free of cirrhosis and hepatocellular carcinoma, and were not on interferon alfa treatment. Also included were a control group of 389 subjects from an iodine-deficient area, another control group of 268 persons living in an area of iodine sufficiency, and 86 patients >40 years of age with chronic hepatitis B.

Levels of thyroid-stimulating hormone (TSH), free thyroxine (T(4)), and triiodothyronine (T(3)), as well as anti-thyroglobulin and anti-thyroid peroxidase antibodies, were measured.

Results

Mean TSH levels were higher (P = 0.001), and free T(3) and free T(4) levels were lower (P <0.0001), in patients with chronic hepatitis C than in all other groups. Patients with chronic hepatitis C were more likely to have hypothyroidism (13% [n = 82]), anti-thyroglobulin antibodies (17% [n = 108]), and anti-thyroid peroxidase antibodies (21% [n = 132]) than were any of the other groups.

Conclusions

Both hypothyroidism and thyroid autoimmunity are more common in patients with chronic hepatitis C, even in the absence of cirrhosis, hepatocellular carcinoma, or interferon treatment, than in normal controls or those with chronic hepatitis B infection.

Department of Internal Medicine and CNR Institute of Clinical Physiology, University of Pisa School of Medicine, Pisa, Italy. a.antonelli@med.unipi.it

06/30/04

Varices

Bleeding Varices:

Swollen veins which can bleed, especially in the esophagus

Factors predicting the presence of esophageal or gastric varices in patients with advanced liver disease. Zaman A, Hapke R, Flora K, Rosen HR, Benner K Department of Medicine, Oregon Health Sciences University, Portland 97201, USA. OBJECTIVE: Recently it has been recommended that all cirrhotic patients without previous variceal hemorrhage undergo endoscopic screening to detect varices and that those with large varices should be treated with beta-blockers (American College of Gastroenterology guidelines). However, endoscopic screening only of patients at highest risk for varices may be the most cost effective. METHODS: Ninety-eight patients without a history of variceal hemorrhage underwent esophagogastroduodenoscopy as part of a liver transplant evaluation. Univariate/multivariate analysis was used to evaluate associations between the presence of varices and patient characteristics including etiology of liver disease, Child-Pugh class, physical findings (spider angiomata, splenomegaly, and ascites), encephalopathy, laboratory parameters (prothrombin time, albumin, bilirubin, BUN, creatinine, and platelets), and abdominal ultrasound findings (portal vein diameter/flow, splenomegaly, and ascites). RESULTS: The causes of cirrhosis among the 67 men and 31 women (mean age, 48 yr) included 28% Hepatitis C/alcoholism, 25% Hepatitis C, 13% alcoholism, 9% primary sclerosing cholangitis/primary biliary cirrhosis, 9% cryptogenic, 6% Hepatitis B, 1% Hepatitis B and C, and 9% other. Patients were Child-Pugh class A 34%, B 51%, and C 15%. Endoscopic findings included esophageal varices in 68% of patients (30% were large), gastric varices in 15%, and portal hypertensive gastropathy in 58%. Platelet count <88,000 was the only parameter identified by univariate/multivariate analysis (p <88,000 is associated with the presence of esophagogastric varices. A large prospective study is needed to verify and validate these findings and may allow identification of a group of patients who would most benefit from endoscopic screening for varices.

Vasculitis

A painful, debilitating condition characterized by inflamed blood vessels -- also common in HCV patient and is thought to be triggered by HCV.

A Painful Connection: HCV and Neuropathy

By Roger Smith

People with Hepatitis C who suffer numbness or tingling in their extremities know from experience there is an association between HCV and neuropathy. Increasingly, their claims are finding support: according to medical researchers and clinical physicians, there is a "very strong association" between hepatitis C virus and a blood condition called essential mixed cryoglobulinemia (EMC). Among other symptoms, EMC can cause nervous system abnormalities. Researchers have not yet explained the precise connection between HCV, EMC, and neuropathy, nor have they found significantly effective treatments, but knowledge is sure to increase as more people are diagnosed with HCV and its symptoms increasingly studied.

Neuropathy refers to any disease of the nervous system resulting from localized inflammation of the nerves. If symptoms appear in the body's extremities, the condition is called "peripheral neuropathy," and most HCV-related neuropathies are of this sort. Patients complain of numbness, tingling, and muscle weakness. A physical examination may also reveal decreased deep tendon reflexes. Occasionally, arm and back pain occurs. One patient has even blamed the nerve inflammation for lost teeth.

If symptoms derive from brain malfunction, the condition is an encephalopathy, or central nervous system disease, and the symptoms are more sinister than those of peripheral neuropathy. A team led by George W. Petty reported two cases of encephalopathy in HCV-infected patients in the July 1996 issue of the Mayo Clinic Proceedings. In both cases small vessels in the brain became inflamed, impairing blood flow. One patient had numbness in the right lip, hand, and leg, weakness in the right hand and arm, and word-finding difficulty. The other patient had headaches and seizures, although the latter may have come in part from medication for the headaches.

In both peripheral neuropathy and encephalopathy the key physiologic change is the inflammation of blood vessels (vasculitis). The hepatitis C virus probably does not inflame the blood vessels directly. Instead, the vessels are responding to immune system products floating through the blood stream.

When the body senses an invasion by foreign organisms, such as HCV, chemical responses are triggered. Among those responses are various kinds of immunoglobulin, proteins that help kill the foreigners or regulate the immune response. For some reason -- biologists are not sure why -- these immunoglobulins can "glob" together and lodge on the walls of medium and small blood vessels.

The immunoglobulins that are involved are called cryoglobulins because they turn into a gel at cool temperatures (cryo comes from the Greek word for cold). Since cold temperature readily affects the small and middle-sized vessels in the body's extremities, the cryoglobulins are most likely to form in them. It appears that this glob-and-lodge action causes the inflammation of blood vessels. Cryoglobulinemia is the condition of having cryoglobulins in the blood.

Cryoglobulinemia and HCV became linked when researchers found bits of HCV and HCV-specific antibodies trapped in globs of cryoglobulin. They speculated that the cryoglobulinemia was HCV-incited, occurring when cryoglobulins specifically attacked the hepatitis virus. Other organisms can cause cryoglobulinemia -- cancerous lymph cells, for instance -- but the HCV-related version always involves a particular mixture of two types of immunoglobulins. Hence, the "essential mixed" of EMC.

However, the link between HCV and EMC is not entirely straightforward. The chemical tests used to identify specific immunoglobulins and the blood assays used to spot HCV products are complex. Doctors do not order them routinely. As for neuropathies, unless there is an obvious reason to suppose they result from HCV infection, doctors are likely to assume that another, more common system-disturbing disease is responsible. Diabetes mellitus may cause very similar symptoms, for instance.

Medical journals have described only a few cases of the HCV-EMC-neuropathy connection. Reviews of the published literature found that 36 to 54 percent of HCV-infected subjects also had cryoglobulins. According to one study, 21 percent of those with the cryoglobulins showed symptoms, but the authors did not specifically mention neuropathy.

The article by Petty's research team cited a handful of other reported cases of HCV-associated cerebral ischemia similar to their two but added that no detailed description of the condition is available. All the articles warn that their findings are exploratory, not definitive.

The experience of clinical gastroenterologists agrees with the research estimates. Mark Schiele, M.D., a gastroenterologist for Health First, Inc., in Portland, Oregon, estimates that fewer than one percent of HCV patients develop neuropathy. "In general," he said, "it's thought to be quite an uncommon manifestation of HCV infection." Sandra Wilborn, M.D., also a Health First gastroenterologist, concurs. "It's not something that has been clinically important to my practice," she said. In fact, Dr. Wilborn has seen only four cases of cryoglobulinemia altogether, and she encountered them before research uncovered the HCV-EMC link. She typically cares for 25 new HCV-infected patients a year.

Dr. Wilborn emphasizes that the long-term effects of HCV infection are only slowly becoming clear because HCV is so recent a discovery. First identified in 1989 as a distinct viral type, HCV usually takes years to become symptomatic. Most patients are diagnosed with chronic HCV ten to 13 years following infection. Typically, about 20 years pass before the most common serious result, liver cirrhosis, appears. But, Dr. Wilborn points out, the virus causes a "cascade effect" from the immune system, and the symptoms that might come from the cascade, including neuropathy, are just beginning to surface in sufficient numbers to study.

It is a good thing that EMC-related neuropathy is uncommon, according to Dr. Schiele, because "it can be a very disabling consequence of viral infection."

The standard treatment for HCV with EMC-caused neuropathy is interferon alfa, which is also the standard treatment for uncomplicated chronic HCV. Unfortunately, interferon alfa treatment eases EMC symptoms in only about one half to two-thirds of patients, and the side effects include headaches, cognitive changes, irritability, and depression. Still, current research supports long-term treatment with interferon alfa.

There are several possible new treatments in the pipeline, either used alone or in combination with interferon alfa. Ribavirin combined with interferon alfa apparently can trick the hepatitis C virus into becoming harmless by mimicking part of its RNA structure, although on its own ribavirin treatment has proven only partially effective. The antiviral agent amantadine has shown promise in clinical trials, and researchers are developing several HCV-specific protease inhibitors similar to those used to quell HIV retrovirus.

Sources

Mark Schiele, M.D., Gastroenterologist, Health First Medical Group, Portland, OR.

Wilson Disease

An inherited (autosomal recessive) disorder where there is excessive quantities of copper in the tissues, particularly the liver and central
nervous system. Wilson's disease causes the body to absorb and retain copper. The copper deposits in the liver, brain, kidneys and eyes.  Complications include dementia and liver failure.

The first part of the body that copper affects is the liver. In about half of Wilson's Disease patients the liver is the only affected organ. The initial physical changes in the liver are only visible under the microscope. When hepatitis develops, patients are often thought to have infectious hepatitis or infectious mononucleosis when they actually have Wilson's Disease hepatitis. Testing for Wilson's Disease should be performed in individuals with unexplained, abnormal liver tests.

http://www.wilsonsdisease.org