Thyroid disease

Symptoms of the condition vary with type: hypo- vs. hyperthyroidism, which are further described below. Possible symptoms of hypothyroidism are: Possible symptoms of hyperthyroidism are: Note: certain symptoms and physical changes can be seen in both hypothyroidism and hyperthyroidism —fatigue, fine / thinning hair, menstrual cycle irregularities, muscle weakness / aches (myalgia), and different forms of myxedema. ==Diseases==

Low function Hypothyroidism is a state in which the body is not producing enough thyroid hormones, or is not able to respond to / utilize existing thyroid hormones properly. The main categories are: • Thyroiditis: an inflammation of the thyroid gland • Hashimoto's thyroiditis / Hashimoto's disease • Ord's thyroiditis • Postpartum thyroiditis • Silent thyroiditis • Acute thyroiditis • Riedel's thyroiditis (the majority of cases do not affect thyroid function, but approximately 30% of cases lead to hypothyroidism) • Iatrogenic hypothyroidism • Postoperative hypothyroidism • Medication- or radiation-induced hypothyroidism • Thyroid hormone resistance • Euthyroid sick syndrome • Congenital hypothyroidism: a deficiency of thyroid hormone from birth, which untreated can lead to cretinism High function Hyperthyroidism is a state in which the body is producing too much thyroid hormone. The main hyperthyroid conditions are: • Graves' disease • Toxic thyroid nodule • Thyroid storm • Toxic nodular struma (Plummer's disease) • Hashitoxicosis: transient hyperthyroidism that can occur in Hashimoto's thyroiditis Structural abnormalities • Goiter: an abnormal enlargement of the thyroid gland • Endemic goiter • Diffuse goiter • Multinodular goiter • Lingual thyroid • Thyroglossal duct cyst Tumors • Thyroid cancer • Papillary • Follicular • Medullary • Anaplastic • Lymphomas are usually malignant • Thyroid adenomas are benign tumors Medication side effects Certain medications can have the unintended side effect of affecting thyroid function. While some medications can lead to significant hypothyroidism or hyperthyroidism and those at risk will need to be carefully monitored, some medications may affect thyroid hormone lab tests without causing any symptoms or clinical changes, and may not require treatment. The following medications have been linked to various forms of thyroid disease: • Amiodarone (more commonly can lead to hypothyroidism, but can be associated with some types of hyperthyroidism) • Lithium salts (hypothyroidism) • Some types of interferon and IL-2 (thyroiditis) • Glucocorticoids, dopamine agonists, and somatostatin analogs (block TSH, which can lead to hypothyroidism) == Pathophysiology ==

Most thyroid disease in the United States stems from a condition where the body's immune system attacks itself. In other instances, thyroid disease comes from the body trying to adapt to environmental conditions like iodine deficiency or to new physiologic conditions like pregnancy. == Autoimmune Thyroid Disease ==

Autoimmune thyroid disease is a general category of disease that occurs due to the immune system targeting its own body. It is not fully understood why this occurs, but it is thought to be partially genetic as these diseases tend to run in families. During pregnancy, there is also an increase in estrogen which causes the mother to produce more thyroxine binding globulin, which is what carries most of the thyroid hormone in the blood. These normal hormonal changes often make pregnancy look like a hyperthyroid state but may be within the normal range for pregnancy, so it necessary to use trimester specific ranges for TSH and free T4. True hyperthyroidism in pregnancy is most often caused by an autoimmune mechanism from Graves' Disease. New diagnosis of hypothyroidism in pregnancy is rare because hypothyroidism often makes it difficult to become pregnant in the first place. When hypothyroidism is seen in pregnancy, it is often because an individual already has hypothyroidism and needs to increase their levothyroxine dose to account for the increased thyroxine binding globulin present in pregnancy. ==Diagnosis==

Diagnosis of thyroid disease depends on symptoms and whether or not a thyroid nodule is present. Most patients will receive a blood test. Others might need an ultrasound, biopsy or a radioiodine scanning and uptake study. Blood tests Thyroid function tests There are several hormones that can be measured in the blood to determine how the thyroid gland is functioning. These include the thyroid hormones triiodothyronine (T3) and its precursor thyroxine (T4), which are produced by the thyroid gland. Thyroid-stimulating hormone (TSH) is another important hormone that is secreted by the anterior pituitary cells in the brain. Its primary function is to increase the production of T3 and T4 by the thyroid gland. The most useful marker of thyroid gland function is serum thyroid-stimulating hormone (TSH) levels. TSH levels are determined by a classic negative feedback system in which high levels of T3 and T4 suppress the production of TSH, and low levels of T3 and T4 increase the production of TSH. TSH levels are thus often used by doctors as a screening test, where the first approach is to determine whether TSH is elevated, suppressed, or normal. • Elevated TSH levels can signify inadequate thyroid hormone production (hypothyroidism) • Suppressed TSH levels can point to excessive thyroid hormone production (hyperthyroidism) Because a single abnormal TSH level can be misleading, T3 and T4 levels must be measured in the blood to further confirm the diagnosis. When circulating in the body, T3 and T4 are bound to transport proteins. Only a small fraction of the circulating thyroid hormones are unbound or free, and thus biologically active. T3 and T4 levels can thus be measured as free T3 and T4, or total T3 and T4, which takes into consideration the free hormones in addition to the protein-bound hormones. Free T3 and T4 measurements are important because certain drugs and illnesses can affect the concentrations of transport proteins, resulting in differing total and free thyroid hormone levels. There are differing guidelines for T3 and T4 measurements. • Free T4 levels should be measured in the evaluation of hypothyroidism, and low free T4 establishes the diagnosis. T3 levels are generally not measured in the evaluation of hypothyroidism. • Free T4 and total T3 can be measured when hyperthyroidism is of high suspicion as it will improve the accuracy of the diagnosis. Free T4, total T3 or both are elevated and serum TSH is below normal in hyperthyroidism. If the hyperthyroidism is mild, only serum T3 may be elevated and serum TSH can be low or may not be detected in the blood. • Free T4 levels may also be tested in patients who have convincing symptoms of hyper- and hypothyroidism, despite a normal TSH. Antithyroid antibodies Autoantibodies to the thyroid gland may be detected in various disease states. There are several anti-thyroid antibodies, including anti-thyroglobulin antibodies (TgAb), anti-microsomal/anti-thyroid peroxidase antibodies (TPOAb), and TSH receptor antibodies (TSHRAb). • Elevated calcitonin levels in the blood have been shown to be associated with the rare medullary thyroid cancer. However, the measurement of calcitonin levels as a diagnostic tool is currently controversial due to falsely high or low calcitonin levels in a variety of diseases other than medullary thyroid cancer. • Very infrequently, TBG and transthyretin levels may be abnormal; these are not routinely tested. • To differentiate between different types of hypothyroidism, a specific test may be used. Thyrotropin-releasing hormone (TRH) is injected into the body through a vein. This hormone is naturally secreted by the hypothalamus and stimulates the pituitary gland. The pituitary responds by releasing thyroid-stimulating hormone (TSH). Large amounts of externally administered TRH can suppress the subsequent release of TSH. This amount of release-suppression is exaggerated in primary hypothyroidism, major depression, cocaine dependence, amphetamine dependence and chronic phencyclidine abuse. There is a failure to suppress in the manic phase of bipolar disorder. Ultrasound Many people may develop a thyroid nodule at some point in their lives. Although many who experience this worry that it is thyroid cancer, there are many causes of nodules that are benign and not cancerous. If a possible nodule is present, a doctor may order thyroid function tests to determine if the thyroid gland's activity is being affected. If more information is needed after a clinical exam and lab tests, medical ultrasonography can help determine the nature of thyroid nodule(s). There are some notable differences in typical benign vs. cancerous thyroid nodules that can particularly be detected by the high-frequency sound waves in an ultrasound scan. The ultrasound may also locate nodules that are too small for a doctor to feel on a physical exam, and can demonstrate whether a nodule is primarily solid, liquid (cystic), or a mixture of both. It is an imaging process that can often be done in a doctor's office, is painless, and does not expose the individual to any radiation. The main characteristics that can help distinguish a benign vs. malignant (cancerous) thyroid nodule on ultrasound are as follows: Although ultrasonography is a very important diagnostic tool, this method is not always able to separate benign from malignant nodules with certainty. In suspicious cases, a tissue sample is often obtained by biopsy for microscopic examination. Radioiodine scanning and uptake Thyroid scintigraphy, in which the thyroid is imaged with the aid of radioactive iodine (usually iodine-123, which does not harm thyroid cells, or rarely, iodine-131), is performed in the nuclear medicine department of a hospital or clinic. Radioiodine collects in the thyroid gland before being excreted in the urine. While in the thyroid, the radioactive emissions can be detected by a camera, producing a rough image of the shape (a radioiodine scan) and tissue activity (a radioiodine uptake) of the thyroid gland. A normal radioiodine scan shows even uptake and activity throughout the gland. Irregular uptake can reflect an abnormally shaped or abnormally located gland, or it can indicate that a portion of the gland is overactive or underactive. For example, a nodule that is overactive ("hot") -- to the point of suppressing the activity of the rest of the gland—is usually a thyrotoxic adenoma, a surgically curable form of hyperthyroidism that is rarely malignant. In contrast, finding that a substantial section of the thyroid is inactive ("cold") may indicate an area of non-functioning tissue, such as thyroid cancer. The amount of radioactivity can be quantified and serves as an indicator of the metabolic activity of the gland. A normal quantitation of radioiodine uptake demonstrates that about 8-35% of the administered dose can be detected in the thyroid 24 hours later. Overactivity or underactivity of the gland, as may occur with hyperthyroidism or hypothyroidism, is usually reflected in increased or decreased radioiodine uptake. Different patterns may occur with different causes of hypo- or hyperthyroidism. Biopsy A medical biopsy refers to the obtaining of a tissue sample for examination under the microscope or other testing, usually to distinguish cancer from noncancerous conditions. Thyroid tissue may be obtained for biopsy by fine needle aspiration (FNA) or by surgery. Fine needle aspiration has the advantage of being a brief, safe, outpatient procedure that is safer and less expensive than surgery and does not leave a visible scar. Needle biopsies became widely used in the 1980s, though it was recognized that the accuracy of identification of cancer was good, but not perfect. The accuracy of the diagnosis depends on obtaining tissue from all of the suspicious areas of an abnormal thyroid gland. The reliability of fine needle aspiration is increased when sampling can be guided by ultrasound, and over the last 15 years, this has become the preferred method for thyroid biopsy in North America. ==Treatment==

Medication Levothyroxine is a stereoisomer of thyroxine (T4) which is degraded much more slowly and can be administered once daily in patients with hypothyroidism. Radioiodine Radioiodine therapy with iodine-131 can be used to shrink the thyroid gland (for instance, in the case of large goiters that cause symptoms but do not harbor cancer—after evaluation and biopsy of suspicious nodules has been done), or to destroy hyperactive thyroid cells (for example, in cases of thyroid cancer). The iodine uptake can be high in countries with iodine deficiency, but low in iodine sufficient countries. To enhance iodine-131 uptake by the thyroid and allow for more successful treatment, TSH is raised prior to therapy in order to stimulate the existing thyroid cells. This is done either by withdrawal of thyroid hormone medication or injections of recombinant human TSH (Thyrogen), == Epidemiology ==

In the United States, autoimmune inflammation is the most common form of thyroid disease while worldwide hypothyroidism and goiter due to dietary iodine deficiency is the most common. Hypothyroidism affects 3-10% percent of adults, with a higher incidence in women and the elderly. An estimated one-third of the world's population currently lives in areas of low dietary iodine levels. In regions of severe iodine deficiency, the prevalence of goiter is as high as 80%. In areas where iodine-deficiency is not found, the most common type of hypothyroidism is an autoimmune subtype called Hashimoto's thyroiditis, with a prevalence of 1-2%. Although thyroid nodules are common, thyroid cancer is rare. Thyroid cancer accounts for less than 1% of all cancer in the UK, though it is the most common endocrine tumor and makes up greater than 90% of all cancers of the endocrine glands. == See also ==