Thyroid Diseases

Diseases that present as abnormal thyroid function include:

• Hypothyroidism: too little thyroid hormone; slowing of body functions; symptoms include weight gain, dry skin, constipation, cold intolerance, puffy skin, hair loss, fatigue, and menstrual irregularity in women. Severe untreated hypothyroidism, called myxedema, can lead to heart failure, seizures, and coma. In children, hypothyroidism can stunt growth and delay sexual development. Specific types of hypothyroidism include:
  • Congenital hypothyroidism: this condition affects infants from birth; it is caused by inadequate thyroid hormone and is most commonly due to a thyroid gland that is missing, only partially developed, or located in an abnormal part of the body. The rest of the cases are due to a normal-sized or enlarged thyroid that does not function properly or produce sufficient thyroid hormone. Left untreated, this condition can cause delays in physical and intellectual development. Hypothyroidism testing is performed in the United States as part of newborn blood screening programs since early detection and treatment can minimize long-term damage.
  • Hashimoto thyroiditis: the most common cause of hypothyroidism in the United States; it is a chronic autoimmune condition in which the immune response targets the thyroid, causing inflammation and damage and the production of autoantibodies. With Hashimoto thyroiditis, however, the thyroid produces low amounts of thyroid hormone.
  • Iodine deficiency: lack of this element (as iodide) diminishes the ability of the thyroid gland to make enough thyroid hormone. T4 has four iodides and T3 has three. Iodide is present throughout the environment, but most iodide is in sea water and seaweed. People who live in countries with little access to the sea often have iodide deficiency unless their sources of food are supplemented with iodide. Fortunately, iodide is used to fight bacterial growth in many foods (such as iodized salt) and is also in many dietary supplements.
• Hyperthyroidism: too much thyroid hormone; sometimes called "overactive thyroid;" acceleration of body functions; symptoms include increased heart rate, anxiety, weight loss, difficulty sleeping, tremors in the hands, weakness, and sometimes diarrhea. There may be puffiness around the eyes, dryness, irritation, and, in some cases, bulging of the eyes. The affected person may experience light sensitivity and visual disturbances. Because the eyes may not move normally, the person may appear to be staring. Specific types of hyperthyroidism include:
  • Graves disease: the most common cause of hyperthyroidism; it is a chronic autoimmune disorder in which the affected person's immune system produces antibodies that act like TSH, stimulating the thyroid to produce excessive amounts of thyroid hormone.
  • Thyroid tumor: a small benign tumor may become insensitive to the negative feedback of low TSH and continue to produce excess thyroid hormone.
  • Abnormal thyroid stimulation: a tumor of the cells that produce TSH can result in excess thyroid hormone production. Also, human chorionic gonadotropin (hCG), the hormone that supports the growth of the fetus in pregnancy, can act like TSH and sometimes produce hyperthyroidism in pregnant women, especially if their hCG levels are very high.
• Goiter: a visible enlargement of the thyroid gland; in the past, this condition was relatively common and was due to iodine deficiency but, with iodine supplementation of food, the incidence of dietary-related goiters has declined significantly in the U.S. In other parts of the world, however, iodine-related goiters are still common and represent the most common cause of hypothyroidism in some countries. Goiters may compress vital structures of the neck, including the trachea and esophagus. This compression can make it difficult to breathe and swallow. Any of the diseases listed above can cause goiters. A rare cause is thyroid hormone resistance syndrome, in which a mutation in the thyroid hormone receptor decreases thyroid hormone function.
• Thyroiditis: an inflammation of the thyroid gland; it may be associated with either hypo- or hyperthyroidism. It may be painful, feeling like a sore throat, or painless. Thyroiditis may be due to an autoimmune disorder (especially Hashimoto thyroiditis), an infection, exposure to a chemical that is toxic to the thyroid, or due to an unknown cause (idiopathic). Depending on the cause, it can be acute but transient or chronic.

Diseases that present as thyroid tumors include:

• Thyroid nodule: a small lump on the thyroid gland that may be solid or a fluid-filled cyst; these nodules are common and the overwhelming majority of them are harmless. Occasionally, however, thyroid nodules can be cancerous and need to be treated.
• Thyroid cancer: thyroid cancer is fairly common and its incidence has been increasing over the past few decades. The American Cancer Society estimates that about 63,000 new cases will be diagnosed in the U.S. in 2014, making it the 8th most common type of cancer and the fastest growing type. There are four main types of thyroid cancers:
  • Papillary thyroid cancer—about 80% of thyroid cancer cases are papillary. This type affects more women than men and is more common in younger people.
  • Follicular thyroid cancer—about 15% of thyroid cancers are follicular, a more aggressive type of cancer that tends to occur in older women.
  • Anaplastic thyroid cancer, also found in older women, accounts for about 2% of thyroid cancers and tends to be both aggressive and difficult to treat.
  • Medullary thyroid cancer (MTC)—accounts for 3% of thyroid cancers and is malignant; it can spread beyond the thyroid and be difficult to treat if it is not discovered early. MTC produces excess calcitonin and may be found alone or linked with other endocrine cancers in a syndrome called multiple endocrine neoplasia syndrome. The cells that make calcitonin are different from the cells that make thyroid hormone. These may grow in number, resulting in a disorder called C-cell hyperplasia. This is a benign condition that also produces excess calcitonin; it may or may not progress to become medullary thyroid cancer.
  • Lymphoma, a tumor composed of lymphocytes (the cells that produce immunity from bacteria and viruses), can also occur in the thyroid.

See this Infographic on Thyroid Cancer by the Hormone Health Network.

Laboratory Tests

The first test a health practitioner will usually order to detect thyroid dysfunction is a test for thyroid stimulating hormone (TSH). If the TSH level is abnormal, the health practitioner will usually order a test for free thyroxine (free T4) to confirm the diagnosis.

T4 is not very soluble in blood so it is carried by serum proteins. A very small percentage of the total T4 is not bound to protein and it is this fraction that is biologically active. In the past, laboratories estimated the concentration of free T4 by measuring the total T4 and also determining the level of binding proteins. Today, however, it is much more common for laboratories to estimate the free T4 directly using immunoassay.

Sometimes, a test for the other major thyroid hormone, triiodothyroine (free T3), may be ordered as well or all tests may be ordered together as a thyroid panel.

• TSH – to test for hypothyroidism, hyperthyroidism, screen newborns for hypothyroidism, and monitor treatment for thyroid disorders
• Free T4 – to test for hypothyroidism, hyperthyroidism, screen newborns for hypothyroidism, and to monitor treatment of thyroid disease 
• Free T3 – primarily to test for hyperthyroidism, especially when the free T4 is not elevated; when people are iodine-deficient, the thyroid makes much more T3 than T4.

Additional tests that may be performed include:

• Total T4 and total T3 may still be needed in some rare circumstances.
• Thyroid antibodies – to help differentiate different types of thyroiditis and identify autoimmune thyroid conditions
  • Thyroid peroxidase (TPO) antibody—a marker for autoimmune thyroid disease; it can be detected in Graves disease or Hashimoto thyroiditis. It may be especially helpful in early Hashimoto thyroiditis when the TSH is elevated but the remaining thyroid is still able to maintain a normal free T4 level.
  • Thyroglobulin (TG) antibody—also a marker for both Graves disease and Hashimoto thyroiditis; this antibody targets thyroglobulin, the storage form of thyroid hormones.
  • Thyroid stimulating hormone receptor (TSHR) antibodies—a marker for Graves disease; these may be measured in two different ways:
  • Some patients with Graves disease have antibodies that can only be detected in one of these two approaches. Rarely, autoimmune antibodies to the TSH receptor can cause hypothyroidism (rather than hyperthyroidism).
• Calcitonin – to help detect the presence of excessive calcitonin production, which can occur with C-cell hyperplasia and medullary thyroid cancer
  • Thyroid stimulating immunoglobulin (TSI) assay measures the stimulation of thyroid cells in a culture dish.
  • Thyroid binding inhibitory immunoglobulin (TBII) assay measures the ability of a person's serum to block TSH from binding to receptors.
• Thyroglobulin – to monitor the treatment of thyroid cancer and to detect recurrence
• Biopsies – often a fine-needle biopsy, a procedure that involves inserting a needle into the thyroid and removing a small amount of tissue and/or fluid from a nodule or other area that the health practitioner wants to examine; an ultrasound is used to guide the needle into the correct position. (See the article on Anatomic Pathology for more general information on biopsies.) If the diagnosis (benign vs. malignant) is unclear, examining the biopsy material with genetic tests for mutations in certain genes (e.g., BRAF, RAS, RET/PTC, Pax8-PPARG, or galectin-3) may help.

Screening

Newborns are routinely screened within days of birth for endocrine disorders, including congenital hypothyroidism. (Read the article on Newborn Screening for more on this.)

Screening for thyroid disease in asymptomatic adults is controversial, and there is no consensus in the medical community as to who would benefit from screening and at what age to begin begin (except for screening in newborn infants, which all recognize is necessary and beneficial). In 2004, the U.S. Preventive Services Task Force found insufficient evidence to recommend for or against routine screening for thyroid disease in asymptomatic adults. However, the American Thyroid Association and the American Association of Clinical Endocrinologists released clinical practice guidelines in 2012 that recommend that screening for hypothyroidism should be considered in people over the age of 60. Because the signs and symptoms of both hypothyroidism and hyperthyroidism are so similar to those seen in many common disorders, health practitioners often need to rule out thyroid disease even though the patient has another problem.

Non-Laboratory Tests

• Thyroid scans – tests that use radioactive iodine or technetium to look for thyroid gland abnormalities and to evaluate thyroid function (for iodine) in different areas of the thyroid
• Ultrasound – an imaging scan that allows health practitioners to determine whether a nodule is solid or fluid-filled and can help measure the size of the thyroid gland

For more on imaging studies, see the web site RadiologyInfo.org.

Treatment for thyroid disease depends on the cause, severity of symptoms, and the levels of hormone production.

Therapy for disorders that cause hyperthyroidism may involve radioactive iodine to destroy part of or the entire thyroid gland to stop excess production, anti-thyroid drugs, or surgery to remove the thyroid. Sometimes all three of these treatments may be used. If the thyroid is destroyed or removed, the person will become hypothyroid and will need to take replacement thyroid hormones to replace what is no longer produced by the thyroid gland.

Treatment for all types and causes of hypothyroidism is usually straightforward and involves thyroid hormone replacement therapy.

Treatment for thyroid cancers depends on the type of cancer and how far it has spread. Thyroid cancer often requires removal of all or part of the thyroid and may involve radioactive iodine treatment and treatment with thyroid hormones. While papillary cancer is usually easily treated and most cases are cured, the others can be a challenge. In some cases, radiation and chemotherapy are used before and after surgical removal of the thyroid.