Thyroid gland

Definition

The thyroid gland is a bilobed organ of the endocrine system located in the front of the neck. It secretes hormones that are involved in human development, growth, and metabolism .

Description

The thyroid gland is a small, butterfly-shaped gland made up of two lobes separated by tissue called the isthmus, which lies across the trachea. The lobes of the thyroid are each approximately 2 inches (5 cm) in length, and the isthmus is approximately 2 inches (5 cm) in width and length and the thyroid gland weighs approximately 1 ounce (28 g). Each lobe of the thyroid gland wraps around and is affixed by fibrous tissue to one side of the trachea. A narrow projection of thyroid tissue, called the pyramidal lobe, is often present and originates at the isthmus and extends up to and lays on the surface of the thyroid cartilage (Adam's apple). The upper projections of the right and left lobes are called the upper poles of the gland while the lower projections of the lobes are called the lower poles. The lobes of the thyroid lie between the larynx and trachea medially and the sternomastoid muscles and carotid sheath laterally. The thyroid gland can be felt through palpitation of the neck, unless the neck is very thick and short or the sternomastoid muscles are very well developed.

A thin capsule of connective tissue surrounds the thyroid and divides it into a cluster of globular sacks called follicles. The gland does not, however, have any true subdivisions, and the follicles are packed together like a bag of berries. The follicles are lined with follicular cells that secrete hormones called thyroxine (T4) and triiodothyronine (T3) and enclose a glutinous material called colloid. Colloid is primarily made of a protein called thyroglobulin that is involved in the formation of T4 and T3. Cells called parafollicluar cells or C-cells, which secrete the hormone calcitonin, are found between the follicles.

Function

T3 and T4 hormones

The primary function of the thyroid gland is to produce and secrete T4 and T3, which are hormones involved in many aspects of growth, development, and metabolism. T4 and T3 are produced from thyroglobulin attached to iodide. Iodine obtained from the diet is absorbed through the small intestine , converted into iodide, and transported through the blood stream to the thyroid. The iodide absorbed by the thyroid attaches to thyroglobulin and forms monoiodotyrosine (MIT) and diiodotyrosine (DIT). T4 is formed when two DITs join together and T3 is formed when one MIT joins to one DIT. At this point the T3/T4 are still attached to the thyroglobulin. The thyroglobulin containing T4 and T3 is then transported to the center of the follicle where it forms colloid. When there are low levels of T4 and T3 in the blood, the follicular cells are stimulated to ingest colloid, and digest the thyroglobulin. This ultimately results in the release of T4 and T3 into the blood stream.

REGULATION OF T3 AND T4 SYNTHESIS AND RELEASE. Thyroid stimulating hormone (TSH), which is also called thyrotropin, is the main regulator of thyroid hormone synthesis and release. TSH is produced by the pituitary gland . Binding of TSH to receptors on the thyroid gland stimulates the synthesis and release of T4 and T3. High concentrations of TSH result in increased thyroid hormone synthesis and release into the blood stream, and low levels of TSH result in decreased synthesis and decreased release into the blood stream. The amount of TSH secreted is controlled by the thyroid-releasing hormone, which is produced by an organ called the hypothalamus. When the amount of thyroid hormones in the blood exceeds a certain level, the hypothalamus stops secreting thyroid-releasing hormone. This stops the secretion of TSH, which stops the secretion of T3 and T4. This is called a negative feedback loop. When the levels of thyroid hormones in the blood stream decrease to below a predetermined level then the negative feedback is stopped and the secretion of thyroid-releasing hormone resumes. This ultimately results in resumed secretion of T4 and T3. The amount of T4 and T3 produced can also be influenced by dietary factors such as the amount of iodine consumed and the total caloric intake and can also be affected by inhibitory drugs such as the thionamides.

Calcitonin

The thyroid gland also secretes calcitonin. The thyroid's C-cells are stimulated to secrete calcitonin when there is a high concentration of calcium in the blood stream. The function of calcitonin is to inhibit the amount

of resorption of calcium from the bone and to regulate the amount of calcium in the blood stream.

Role in human health

The hormones T4 and T3 produced by the thyroid gland are involved in growth, development and metabolism, and it is likely that most cells are targets for these hormones. Some researchers feel that T4 is only an inactive prohormone while T3 is the biochemically active form of the thyroid hormone. Some T3 is produced in the thyroid but most of it is produced from the conversion of T4 outside of the liver . Receptors on cells bind some T4 but preferentially bind T3. The thyroid hormones stimulate the metabolic activities of most tissues and cause an increase in basal metabolic rate. Normal levels of T4 and T3 are necessary for normal development of the brain and normal growth in childhood. The thyroid hormones are also involved in regulating heart rate and increasing cardiac contractility and output. These hormones also have effects on the central nervous system , since decreased thyroid hormone levels are associated with decreased ability to concentrate and think, and increased levels are associated with anxiety . The reproductive system also requires normal thyroid hormone levels, and decreased levels of these hormones can result in infertility .

Common diseases and disorders

Iodine deficiency or excess

Dietary intake of iodine is necessary for the normal synthesis of T3 and T4. A deficiency or excess consumption of iodine can result in a deficiency in these hormones (hypothyroidism) or an excess of these hormones (hyperthyroidism). Iodine deficiency is less common in developed countries where table salt contains iodine. Disorders which lead to a deficiency of iodide in the thyroid can also cause hypothyroidism.

Hypothyroidism

Hypothyroidism is the most common disease of the thyroid and results in deficient production of T4/T3 by the thyroid, or defects, which result in the inability of the body to respond to T4/T3. The clinical manifestations of hypothyroidism include:

• goiter
• fatigue
• constipation
• weight gain
• memory and mental impairment and decreased concentration
• depression
• loss of libido
• coarseness or loss of hair
• dry skin and cold intolerance
• irregular or heavy menses
• infertility
• hoarseness
• myalgias
• hyperlipidemia
• reflex delay
• bradycardia
• hypothermia
• ataxia

Hypothyroidism is usually confirmed when serum levels of T4 are decreased and serum levels of TSH are increased. In some cases, patients with hypothyroidism can have normal T4 or TSH levels or even low TSH levels. Hypothyroidism is typically treated by oral administration of a synthetic form of T4 called levothyroxine. Hypothyroidism can be classified into primary hypothyroidism, central hypothyroidism and peripheral hypothyroidism.

PRIMARY HYPOTHYROIDISM. Primary hypothyroidism is the most common form of hypothyroidism. Primary hypothyroidism is caused by factors affecting the thyroid gland itself such as thyroid dysgenesis, environmental damage to the thyroid, inherited metabolic defects and environmental factors such as medications which affect thyroxin synthesis. Primary hypothyroidism generally results in low serum levels of T4 and high serum levels of TSH.

The most common cause of primary hypothyroidism in adults in developed countries is autoimmune thyroiditis (Hashimoto's thyroiditis). Hashimoto's thyroiditis results when the body forms antibodies against the TSH receptors in the thyroid gland. This results in a decreased stimulation of T4/T3 production by the thyroid gland.

CENTRAL HYPOTHYROIDISM. Central hypothyroidism results from insufficient stimulation of the thyroid gland by the thyroid-stimulating hormone (TSH). Central hypothyroidism can result from abnormalities that interfere with the pituitary release of TSH or factors that affect the regulation of TSH by thyroptin releasing hormone (TRH). Central hypothyroidism generally results in low serum levels of T4 and normal to low serum levels of TSH.

PERIPHERAL HYPOTHYROIDISM. Peripheral hypothyroidism is extremely rare and results when the body is unable to respond to thyroxin. The most common cause is thyroid hormone resistance, a rare, autosomal dominant disorder that results from mutations in the thyroid hormone receptor (Trbeta). Increased secretions of T4 and increased T4 in sera and increased levels of TSH characterize this disorder. Patients with this disorder have a 50% percent chance of passing it on to their offspring. Peripheral hypothyroidism can also be caused by massive infantile hemangiomas that excrete high levels of type 3 deiodinase which inactivates T4.

Congenital hypothyroidism

Infants born with hypothyroidism are said to be affected with congenital hypothyroidism. In addition to the typical manifestations of hypothyroidism, congenital hypothyroidism, if untreated, can cause stunted growth, apathy, distended abdomen, swollen tongue, and mental retardation.

Eighty to 90% of cases of congenital hypothryoidism are caused by thyroid dysgenesis. Ten to 15% are due to inherited inborn errors of thyroid hormonogenesis, which are usually autosomal recessive and have a 25% recurrence risk. Congenital hypothyroidism can sometimes be caused by materal radiation treatment during pregnancy or uncontrolled maternal hypothyroidism or hyperthyroidism during pregnancy.

Hyperthyroidism

Hyperthyroidism results from an excess amount of T4 and T3 in the blood stream. The major symptoms of hyperthyroidism include nervousness, tremors, sweating,

heat intolerance, palpitations, weight loss with normal caloric intake, amenorrhea, and muscle weakness. In the presence of clinical symptoms the diagnosis of hyperthyroidism can be confirmed when serum measurements indicate increased T4 and/or decreased TSH levels. Hyperthyroidism can be treated through medications such as thionamides, which inhibit the synthesis of T4 and T3, and beta blockers which block the action of thyroid hormones on peripheral cells. Patients who cannot be treated through medications are treated through radioiodine destruction of the thyroid or surgical removal of the thyroid. Surgical removal of the thyroid and sometimes radioiodine treatment can leave the patient permanently hypothyroid.

GRAVES' DISEASE. Graves' disease, the most common cause of hyperthyroidism, is an autoimmune disease resulting from the formation of antibodies against the TSH receptors in the thyroid gland. The only difference between Hashimoto's thyroiditis and Graves' disease is that Graves disease results when these antibodies stimulate thyroid hormone synthesis rather than inhibiting it. Graves' disease results in increased synthesis of T4 and T3, and can result in exophthalmos, thyroid enlargement and goiter, and vitilago. People with Graves' disease may pass on a genetic predisposition and a slightly increased chance of developing Graves' disease to their offspring.

KEY TERMS

Adenoma —A benign glandular epithelial tumor.

Autosomal dominant —Mutation of only one gene of a pair is required to cause abnormal functioning.

Autosomal recessive —Mutations in both genes of a pair are required to cause abnormal functioning.

Basal metabolic rate —The number of calories that the body consumes when at rest.

Bradycardia —Slowing of the pulse.

Colloid —The gelatinous material made up primarily of thyroglobulin which is found in the follicles of the thyroid.

Cardiac contractility —The ability of the muscles of the heart to contract in the presence of a stimulus.

Endocrine system —A group of organs that secrete hormones directly into the circulatory system that affect metabolism and other body functions.

Exophthalmos —Protrusion of the eyeball.

Goiter —An enlarged thyroid gland resulting in a swelling on the front of the neck.

Hemangioma —Benign tumor made of newly formed blood vessels.

Hormone —A chemical produced by the body which is involved in regulating specific bodily functions such as growth, development, and reproduction.

Hormonogenesis —The production of hormones.

Lobe —Well defined segment of an organ.

Metabolism —Activity by which cells obtain energy from nutrients or use energy to perform basic body functions.

Thyroglobulin —Protein found in the follicles of the thyroid which is involved in the formation of the T4 and T3 hormones produced by the thyroid.

Trachea —Windpipe.

Vitiligo —A skin disorder characterized by depigmented white patches that can have a hyperpigmented border.

OTHER CAUSES OF HYPERTHYROIDISM. Toxic adenoma of the thyroid results from a thyroid nodule that produces additional T4 and T3. This excess production of thyroid hormones results in increased concentrations of T3 and/or T4 in the blood stream and suppression of TSH. Toxic adenoma can be treated through surgical removal of the thyroid, treatment with radioactive iodine, and injection of ethanol into the nodule.

Hyperthyroidism can also be caused by a toxic multinodular goiter. Toxic multinodular goiter is common in areas of iodine deficiency. The multinodular goiter usually results from a goiter caused by hypothyroidism which eventually develops multiple nodules. These nodules produce excess T4 and T3 hormone independent of the TSH levels. Treatment usually involves radioactive iodine or surgery. Hyperthyroidism can also occasionally be caused from abnormalities such as adenomas of the pituitary gland which result in an increased production of TSH. Infections of the thyroid gland can also result in hyperthyroidism. Uncontrolled maternal hyperthyroidism in pregnancy can cause hyperthyroidism in the fetus. In the past hyperthyroidism was occasionally induced when individuals ingested hamburgers containing ground up bovine thyroid gland.

Resources

BOOKS

Braverman, L. E., and R. D. Utiger, eds. The Thyroid: A Fundamental and Clinical Text. Philadelphia, PA: Lippincott Williams and Wilkins, 2000.

Falk, S.A., ed. Thryoid Disease: Endocrinology, Surgery, Nuclear Medicine and Radiotherapy. 2nd edition. Philadelphia, PA: Lippincott-Raven, 1997.

Fisher, D. A. "Thyroid Disorders." In Principles and Practice of Medical Genetics. Edited by D. L. Rimoin, J. M. Connor, and R. E. Dyeritz. New York: Churchill Livingstone, 1997, pp.1365–1377.

ORGANIZATIONS

The American Thyroid Association, Inc. Townhouse Office Park, 55 Old Nyack Turnpike, Suite 611, Nanuet, NY 10954. Fax: 914–623–3736. <http://www.thyroid.org/>.

OTHER

American Association of Clinical Endocrinology (AACE). Clinical Practice Guidelines for Evaluation and Treatment of Hyperthyrodism and Hypothyroidism. <http://www.aace.com/clin/guides/thyroid_guide.html>(1996).

De Groot, Leslie J and, Georg Hennemann. (eds.) The Thyroid Manager. <http://www.thyroidmanager.org/> (February 1,2001).

Lisa Maria Andres, M.S., CGC

Thyroid Gland

Definition

The thyroid gland is a bilobed organ of the endocrine system located in the front of the neck. It secretes hormones that are involved in human development, growth, and metabolism.

Description

The thyroid gland is a small, butterfly-shaped gland made up of two lobes separated by tissue called the isthmus, which lies across the trachea. The lobes of the thyroid are each approximately 2 inches (5 cm) in length, and the isthmus is approximately 2 inches (5 cm) in width and length. The thyroid gland weighs approximately 1 ounce (28 g). Each lobe of the thyroid gland wraps around and is affixed by fibrous tissue to one side of the trachea. A narrow projection of thyroid tissue, called the pyramidal lobe, is often present and originates at the isthmus and extends up to and lays on the surface of the thyroid cartilage (Adam's apple). The upper projections of the right and left lobes are called the upper poles of the gland while the lower projections of the lobes are called the lower poles. The lobes of the thyroid lie between the larynx and trachea medially and the sternomastoid muscles and carotid sheath laterally. The thyroid gland can be felt through palpitation of the neck, unless the neck is very thick and short or the sternomastoid muscles are very well developed.

A thin capsule of connective tissue surrounds the thyroid and divides it into a cluster of globular sacks called follicles. The gland does not, however, have any true subdivisions, and the follicles are packed together like a bag of berries. The follicles are lined with follicular cells that secrete hormones called thyroxine (T4) and triiodothyronine (T3) and enclose a glutinous material called colloid. Colloid is primarily made of a protein called thyroglobulin that is involved in the formation of T4 and T3. Cells called parafollicular cells or C-cells, which secrete the hormone calcitonin, are found between the follicles.

Function

T3 and T4 hormones

The primary function of the thyroid gland is to produce and secrete T4 and T3, which are hormones involved in many aspects of growth, development, and metabolism. T4 and T3 are produced from thyroglobulin attached to iodide. Iodine obtained from the diet is absorbed through the small intestine, converted into iodide, and transported through the blood stream to the thyroid. The iodide absorbed by the thyroid attaches to thyroglobulin and forms monoiodotyrosine (MIT) and diiodotyrosine (DIT). T4 is formed when two DITs join together, and T3 is formed when one MIT joins to one DIT. At this point the T3/T4 are still attached to the thyroglobulin. The thyroglobulin containing T4 and T3 is then transported to the center of the follicle where it forms colloid. When there are low levels of T4 and T3 in the blood, the follicular cells are stimulated to ingest colloid, and digest the thyroglobulin. This ultimately results in the release of T4 and T3 into the bloodstream.

REGULATION OF T3 AND T4 SYNTHESIS AND RELEASE. Thyroid stimulating hormone (TSH), which is also called thyrotropin, is the main regulator of thyroid hormone synthesis and release. TSH is produced by the pituitary gland. Binding of TSH to receptors on the thyroid gland stimulates the synthesis and release of T4 and T3. High concentrations of TSH result in increased thyroid hormone synthesis and release into the bloodstream, and low levels of TSH result in decreased synthesis and decreased release into the blood stream. The amount of TSH secreted is controlled by the thyroid-releasing hormone, which is produced by an organ called the hypothalamus. When the amount of thyroid hormones in the blood exceeds a certain level, the hypothalamus stops secreting thyroid-releasing hormone. This stops the secretion of TSH, which stops the secretion of T3 and T4. This process is called a negative feedback loop. When the levels of thyroid hormones in the blood stream decrease to below a predetermined level then the negative feedback is stopped and the secretion of thyroid-releasing hormone resumes. This ultimately results in resumed secretion of T4 and T3. The amount of T4 and T3 produced can also be influenced by dietary factors, such as the amount of iodine consumed and the total caloric intake, and can also be affected by inhibitory drugs such as the thionamides.

Calcitonin

The thyroid gland also secretes calcitonin. The thyroid's C-cells are stimulated to secrete calcitonin when there is a high concentration of calcium in the blood stream. The function of calcitonin is to inhibit the amount of resorption of calcium from the bone and to regulate the amount of calcium in the blood stream.

Role in human health

The hormones T4 and T3 produced by the thyroid gland are involved in growth, development, and metabolism, and it is likely that most cells are targets for these hormones. Some researchers feel that T4 is only an inactive prohormone, while T3 is the biochemically active form of the thyroid hormone. Some T3 is produced in the thyroid, but most of it is produced from the conversion of T4 outside of the liver. Receptors on cells bind some T4 but preferentially bind T3. The thyroid hormones stimulate the metabolic activities of most tissues and cause an increase in basal metabolic rate. Normal levels of T4 and T3 are necessary for normal development of the brain and normal growth in childhood. The thyroid hormones are also involved in regulating heart rate and increasing cardiac contractility and output. These hormones also have effects on the central nervous system, since decreased thyroid hormone levels are associated with decreased ability to concentrate and think, and increased levels are associated with anxiety. The reproductive system also requires normal thyroid hormone levels, and decreased levels of these hormones can result in infertility.

Common diseases and disorders

Iodine deficiency or excess

Dietary intake of iodine is necessary for the normal synthesis of T3 and T4. A deficiency or excess consumption of iodine can result in a deficiency in these hormones (hypothyroidism) or an excess of these hormones (hyperthyroidism). Iodine deficiency is less common in developed countries where table salt contains iodine. Disorders which lead to a deficiency of iodide in the thyroid can also cause hypothyroidism.

Hypothyroidism

Hypothyroidism is the most common disease of the thyroid and results in deficient production of T4/ T3 by the thyroid, or defects, which result in the inability of the body to respond to T4/T3. The clinical manifestations of hypothyroidism include:

• goiter
• fatigue
• constipation
• weight gain
• memory and mental impairment and decreased concentration
• depression
• loss of libido
• coarseness or loss of hair
• dry skin and cold intolerance
• irregular or heavy menses
• infertility
• hoarseness
• myalgias
• hyperlipidemia
• reflex delay
• bradycardia
• hypothermia
• ataxia

Hypothyroidism is usually confirmed when serum levels of T4 are decreased and serum levels of TSH are increased. In some cases, patients with hypothyroidism can have normal T4 or TSH levels or even low TSH levels. Hypothyroidism is typically treated by oral administration of a synthetic form of T4 called levothyroxine. Hypothyroidism can be classified into primary hypothyroidism, central hypothyroidism and peripheral hypothyroidism.

PRIMARY HYPOTHYROIDISM. Primary hypothyroidism is the most common form of hypothyroidism. Primary hypothyroidism is caused by factors affecting the thyroid gland itself, such as thyroid dysgenesis, environmental damage to the thyroid, inherited metabolic defects, and environmental factors such as medications that affect thyroxin synthesis. Primary hypothyroidism generally results in low serum levels of T4 and high serum levels of TSH.

The most common cause of primary hypothyroidism in adults in developed countries is autoimmune thyroiditis (Hashimoto's thyroiditis). Hashimoto's thyroiditis results when the body forms antibodies against the TSH receptors in the thyroid gland. This results in a decreased stimulation of T4/T3 production by the thyroid gland.

CENTRAL HYPOTHYROIDISM. Central hypothyroidism results from insufficient stimulation of the thyroid gland by the thyroid-stimulating hormone (TSH). Central hypothyroidism can result from abnormalities that interfere with the pituitary release of TSH or factors that affect the regulation of TSH by thyropin releasing hormone (TRH). Central hypothyroidism generally results in low serum levels of T4 and normal to low serum levels of TSH.

PERIPHERAL HYPOTHYROIDISM. Peripheral hypothyroidism is extremely rare and results when the body is unable to respond to thyroxin. The most common cause is thyroid hormone resistance, a rare, autosomal dominant disorder that results from mutations in the thyroid hormone receptor (Trbeta). Increased secretions of T4 and increased T4 in sera and increased levels of TSH characterize this disorder. Patients with this disorder have a 50% chance of passing it on to their offspring. Peripheral hypothyroidism can also be caused by massive infantile hemangiomas that excrete high levels of type 3 deiodinase, which inactivates T4.

Congenital hypothyroidism

Infants born with hypothyroidism are said to be affected with congenital hypothyroidism. In addition to the typical manifestations of hypothyroidism, congenital hypothyroidism, if untreated, can cause stunted growth, apathy, distended abdomen, swollen tongue, and mental retardation.

Eighty to 90% of cases of congenital hypothyroidism are caused by thyroid dysgenesis. Ten to 15% are due to inherited inborn errors of thyroid hormonogenesis, which are usually autosomal recessive and have a 25% recurrence risk. Congenital hypothyroidism can sometimes be caused by maternal radiation treatment during pregnancy or uncontrolled maternal hypothyroidism or hyperthyroidism during pregnancy.

Hyperthyroidism

Hyperthyroidism results from an excess amount of T4 and T3 in the bloodstream. The major symptoms of hyperthyroidism include nervousness, tremors, sweating, heat intolerance, palpitations, weight loss with normal caloric intake, amenorrhea, and muscle weakness. In the presence of clinical symptoms, the diagnosis of hyperthyroidism can be confirmed when serum measurements indicate increased T4 and/or decreased TSH levels. Hyperthyroidism can be treated through medications such as thionamides, which inhibit the synthesis of T4 and T3; and beta blockers, which block the action of thyroid hormones on peripheral cells. Patients who cannot be treated with medications are treated through radioiodine destruction of the thyroid or surgical removal of the thyroid. Surgical removal of the thyroid and sometimes radioiodine treatment can leave the patient permanently hypothyroid.

GRAVES' DISEASE. Graves' disease, the most common cause of hyperthyroidism, is an autoimmune disease resulting from the formation of antibodies against the TSH receptors in the thyroid gland. The only difference between Hashimoto's thyroiditis and Graves' disease is that Graves' disease results when these antibodies stimulate thyroid hormone synthesis rather than inhibiting it. Graves' disease results in increased synthesis of T4 and T3, and can result in exophthalmos, thyroid enlargement and goiter, and vitiligo. People with Graves' disease may pass on a genetic predisposition and a slightly increased chance of developing Graves' disease to their offspring.

OTHER CAUSES OF HYPERTHYROIDISM. Toxic adenoma of the thyroid results from a thyroid nodule that produces additional T4 and T3. This excess production of thyroid hormones results in increased concentrations of T3 and/or T4 in the bloodstream and suppression of TSH. Toxic adenoma can be treated through surgical removal of the thyroid, treatment with radioactive iodine, and injection of ethanol into the nodule.

Hyperthyroidism can also be caused by a toxic multinodular goiter. Toxic multinodular goiter is common in areas of iodine deficiency. The multinodular goiter usually results from a goiter caused by hypothyroidism that eventually develops multiple nodules. These nodules produce excess T4 and T3 hormone independent of the TSH levels. Treatment usually involves radioactive iodine or surgery. Hyperthyroidism can also occasionally be caused from abnormalities such as adenomas of the pituitary gland, which result in an increased production of TSH. Infections of the thyroid gland can also result in hyperthyroidism. Uncontrolled maternal hyperthyroidism in pregnancy can cause hyperthyroidism in the fetus. In the past hyperthyroidism was occasionally induced when individuals ingested hamburgers containing ground up bovine thyroid gland.

KEY TERMS

Adenoma— A benign glandular epithelial tumor.

Autosomal dominant— Mutation of only one gene of a pair is required to cause abnormal functioning.

Autosomal recessive— Mutations in both genes of a pair are required to cause abnormal functioning.

Basal metabolic rate— The number of calories that the body consumes when at rest.

Bradycardia— Slowing of the pulse.

Colloid— The gelatinous material made up primarily of thyroglobulin which is found in the follicles of the thyroid.

Cardiac contractility— The ability of the muscles of the heart to contract in the presence of a stimulus.

Endocrine system— A group of organs that secrete hormones directly into the circulatory system and affect metabolism and other body functions.

Exophthalmos— Protrusion of the eyeball.

Goiter— An enlarged thyroid gland resulting in a swelling on the front of the neck.

Hemangioma— Benign tumor made of newly formed blood vessels.

Hormone— A chemical produced by the body which is involved in regulating specific bodily functions such as growth, development, and reproduction.

Hormonogenesis— The production of hormones.

Lobe— Well defined segment of an organ.

Metabolism— Activity by which cells obtain energy from nutrients or use energy to perform basic body functions.

Thyroglobulin— Protein found in the follicles of the thyroid which is involved in the formation of the T4 and T3 hormones produced by the thyroid.

Trachea— Windpipe.

Vitiligo— A skin disorder characterized by depigmented white patches that can have a hyperpigmented border.

Resources

BOOKS

Braverman, L. E., and R. D. Utiger, eds. The Thyroid: A Fundamental and Clinical Text. Philadelphia, PA: Lippincott Williams and Wilkins, 2000.

Falk, S.A., ed. Thryoid Disease: Endocrinology, Surgery, Nuclear Medicine and Radiotherapy, 2nd edition. Philadelphia, PA: Lippincott-Raven, 1997.

Fisher, D. A. "Thyroid Disorders." In Principles and Practice of Medical Genetics. Edited by D. L. Rimoin, J. M. Connor, and R. E. Dyeritz. New York: Churchill Livingstone, 1997, pp.1365-1377.

ORGANIZATIONS

The American Thyroid Association, Inc. Townhouse Office Park, 55 Old Nyack Turnpike, Suite 611, Nanuet, NY 10954. Fax: 914-623-3736. 〈http://www.thyroid.org/〉.

OTHER

American Association of Clinical Endocrinology (AACE). Clinical Practice Guidelines for Evaluation and Treatment of Hyperthyroidism and Hypothyroidism. 〈http://www.aace.com/clin/guides/thyroid_guide.html〉 (1996).

De Groot, Leslie J., and Georg Hennemann, eds. The Thyroid Manager. 〈http://www.thyroidmanager.org/〉 (February 1, 2001).

thyroid gland The thyroid gland secretes hormones which are necessary for normal growth and development from fetal life onwards, and for maintenance of normal metabolism in the adult body.

The gland is located just below the larynx and attached to the front of the trachea. The adult gland weighs 10–20 g and consists of two relatively flat oval lobes linked by an isthmus. It is so named because of its resemblance to the classical shield (thureos) used by the ancient Greeks. However, unlike the shield, in any one individual the thyroid is generally asymmetric, with the right lobe being significantly larger than the left. The gland is usually larger in women than in men and it increases slightly in size during pregnancy. This is exploited as an early pregnancy test in some African communities: the neck of a bride is adorned with a tight necklace and pregnancy is indicated when in due course the necklace is broken by the swelling thyroid gland.

The embryonic thyroid originated in the floor of the pharynx and it can be detected as a midline thickening, as early as day 24. By weeks 6–7 the characteristic bilobed structure can be distinguished. At about this time, the gland becomes detached from the pharynx and the developing tissue mass descends into the neck. The two lobes finally come to rest on either side of the trachea with the joining isthmus lying across the front of it. Occasionally the thyroid fails to descend, or may descend too far; the fully developed gland is then found below the root of the tongue or within the thorax. Such developmental abnormalities do not necessarily affect thyroid function.

During its descent down the neck the developing thyroid incorporates ‘C-cells’ into its tissue mass; also two pairs of discrete parathyroid glands become attached to the back surface of the thyroid gland itself. These secrete hormones which regulate the concentration of calcium in the blood: the C-cells secrete the protein calcitonin, and the parathyroids the protein parathyroid hormone. Neither of these are regarded as thyroid hormones since they are not produced by the main mass of thyroid tissue; the latter consists of spherical follicles where the thyroid hormones are synthesized and stored.

The major functional and structural unit of the thyroid is the thyroid follicle. There are many thousands of follicles, and their individual sizes vary considerably, ranging in diameter from 20 to 100 μm (2/100–1/10 mm). A rich network of fenestrated capillary blood vessels surrounds small groups of follicles and there is an impressively high rate of blood flow through the gland as a whole (per unit mass, the flow is twice the flow through the kidneys, which themselves have a much greater blood supply than other organs relative to their size). The even greater flow through an overactive thyroid produces a ‘bruit’ which can be heard when a stethoscope is placed over the gland. The high blood flow ensures an adequate supply of blood-borne nutrients to the follicles — in particular the delivery of iodide derived from the diet — as well as uptake of the thyroid hormones into the bloodstream.

The unique biochemical characteristic of thyroid follicular cells is their ability to concentrate and to utilize dietary iodide. The cell possesses an iodide ‘pump’ which enables it to accumulate iodide internally, so that it can achieve a concentration twenty- to a hundred-fold higher than that in the circulating blood. Two other tissues which share a closely related embryonic origin with the thyroid (some cells of the stomach lining and the salivary glands) also possess this pumping mechanism, but the thyroid is unique in its ability to retain and utilize the iodide for the biosynthesis of its hormones. These hormones are small molecules derived from the amino acid tyrosine and they have iodine incorporated into their structures. There are two thyroid hormones, which have either 3 or 4 atoms of iodine per molecule; they are known respectively as T₃ (tri-iodothyronine) and T₄ (thyroxine). Both are synthesized within the thyroid follicles and secreted into the bloodstream when the cells are stimulated to extrude them by the thyroid stimulation hormone (TSH) from the pituitary gland. The thyroid hormones in the circulation in turn regulate the production of TSH by the pituitary, switching off TSH production when the appropriate level of T_3/T₄ is attained in the blood. Thus the ‘pituitary–thyroid axis’ is a classical example of a negative feedback system.

Following the accumulation of iodine in the follicular cells, the T₃ and T₄ are first synthesized separately and are then incorporated into a much larger molecule known as thyroglobulin. This large glycoprotein, which is sometimes referred to as ‘colloid’ is stored in the hollow interior of each follicle. If a thyroid gland which has been removed is cut across and gently squeezed, the colloid can be observed leaking from the transected follicles as a glistening yellowish fluid. TSH stimulates the release of the T₃ and T₄ from the thyroglobulin so that the hormones can be secreted from the cells into the bloodstream in a regulated fashion. This hormone storage system is unique in endocrine physiology; it ensures that there is a two-month supply of thyroid hormones in the event that a person encounters an iodine deficient environment. This occurs in many parts of the world, such as some mountainous regions in China and India. However, this capacity to store thyroid hormones within the follicles as thyroglobulin becomes disadvantageous if an individual inadvertently ingests radioactive iodine. This occurred after the huge release into the atmosphere of radioactive isotopes, including radioiodine, during the week following the Chernobyl accident on 26 April 1986. The natural storage of the radioiodine in the follicles delays clearance of the ingested radionuclide and concentrates the damaging radiation on the thyroid. In Belarus and the Ukraine this resulted in a major increase in the incidence of thyroid cancer in the 1990s amongst children born before the accident.

Thyroid hormones circulate in the blood in minute concentrations (nanomolar — of the order of 10^-9 × molecular weight per litre). Although this is very low compared with many blood constituents such as glucose or sodium ions, which circulate at millimolar concentrations (a million times greater), it is high relative to hormones in general. The blood concentrations of the thyroid hormones are tightly regulated by TSH and remain very stable in a healthy individual over prolonged periods. Thyroid hormones are relatively insoluble in water and this has two important consequences. Firstly, in the circulation more than 99% of them are linked to specific ‘binding proteins’; this prolongs their half-life in blood, and since the binding is reversible, maintains a biologically active ‘reservoir’ in the circulation. Secondly, on arrival at a target cell, the hormones, being relatively soluble in lipid, are able to cross the plasma membrane of the cell and then bind to specific receptors associated with gene regulation in the nucleus of the cell.

Thyroid hormones regulate the activities of almost all cells in the body. They exert three main classes of action. Firstly they control the basal metabolic rate (BMR). Secondly they influence cell differentiation and growth. Thirdly they may modify the action of other hormones, extending their importance still more widely. Thus a lack of thyroid hormones is manifested in diverse ways. In the developing fetus an inadequate supply leads to impaired brain development with the danger of the infant being borne a cretin. In an adult there is a depressed BMR with attendant lethargy. By contrast, excess thyroid hormones raise the BMR and may lead to cardiac problems due to potentiation by thyroid hormone of the effects of adrenaline.

T₃, the form of thyroid hormone which contains only 3 atoms of iodine per molecule, is now considered to be the physiologically active hormone, and T₄ to be a precursor of T₃, which can be converted to T₃ by specific enzymes within the target cells. Since T₄ circulates at a concentration about a hundred-fold higher than that of T₃, it can therefore be considered to be a storage form of the active hormone. Thus the thyroid system as a whole is designed to buffer any possibility of a reduction in the adequate supply of T₃ to target cells: large reserves are maintained in the thyroglobulin stored in the follicles, in the T₃ and T₄ attached to the circulating binding proteins, and in T₄ itself.

N. J. Marshall

Thyroid Gland

The thyroid gland, the largest of the endocrine glands, is located in the neck just below the thyroid cartilage of the larynx . It consists of two lobes, one on either side of the trachea, joined by a narrow band or isthmus. It is composed of numerous hollow ball-shaped follicles with small, interspersed clusters of parafollicular cells.

Follicle cells concentrate and attach iodine to the amino acid tyrosine, producing two forms of thyroid hormone (TH): thyroxine or tetraiodothyronine (T₄), and smaller amounts of triiodothyronine (T₃). Manufacture and release of these hormones into the blood is regulated by thyroid stimulating hormone, TSH, from the pituitary gland. The major effect of TH is to stimulate activity of enzymes involved in energy production through the oxidation (burning) of glucose , thus increasing basal metabolic rate. A side effect of this increased activity is the production of body heat.

Overactivity of the thyroid gland, called hyperthyroidism, causes elevated metabolic rate, nervousness, and weight loss. The most common form of hyperthyroidism, Graves' disease, is an autoimmune disease ; it is accompanied by swelling of the thyroid (goiter) and bulging of the eyes (exophthalmos). Adult hypothyroidism, or underactive thyroid, causes myxedema , characterized by lowered metabolic rate, sluggishness, and weight gain. Additional consequences of low TH levels in infants are stunted growth and irreversible brain damage. Hypothyroidism resulting from low iodine intake, with consequent low TH manufacture, produces an enlargement of the thyroid gland called endemic goiter. TSH is responsible for this enlargement.

Parafollicular cells produce the hormone calcitonin, which lowers blood calcium levels by suppressing the activity of bone-destroying cells called osteoclasts, and stimulating calcium uptake by bones. Calcitonin is important in children, where growing bones are being constantly remodeled. It has little effect on the normal adult skeleton, but may be prescribed in nasal spray form to help reduce bone destruction in osteoporosis. Parathormone, produced by the parathyroid gland, has opposing effects on blood calcium levels.

see also Autoimmune Disease; Bone; Endocrine System; Hormones; Metabolism, Human

Patricia L. Dementi

Bibliography

Marieb, Elaine Nicpon. Human Anatomy and Physiology, 5th ed. Boston: Addison-Wesley-Longman, 2001.

Saladin, Kenneth S. Anatomy and Physiology: The Unity of Form and Function, 2nd ed. Boston: McGraw-Hill, 2001.

thy·roid / ˈ[unvoicedth]īˌroid/ • n. 1. (also thyroid gland) a large ductless gland in the neck that secretes hormones regulating growth and development through the rate of metabolism. ∎  an extract prepared from the thyroid gland of animals and used in treating deficiency of thyroid hormones.2. (also thyroid cartilage) a large cartilage of the larynx, a projection of which forms the Adam's apple in humans.