Parathyroid glands

Definition

The four parathyroid glands are small, light-colored lumps protruding from the surface of the thyroid gland . They secrete parathyroid hormone, the most important regulator of calcium and phosphorus amounts in the body.

Description

The parathyroid glands are located on the thyroid gland, a butterfly-shaped gland found in the neck on both sides of the windpipe. There are then two parathyroid glands on each side of the neck for a total of four. Parathyroid tissue consists of two major cell types: oxyphil cells, whose function is unknown, and chief cells, which produce parathyroid hormone. The structure of a parathyroid gland is very different from that of a thyroid gland. The chief cells that produce parathyroid hormone are arranged in tightly-packed nests around small blood vessels , quite unlike the thyroid cells that produce thyroid hormones, which are arranged in spheres (thyroid follicles).

The parathyroid glands secrete parathyroid hormone (PTH), a polypeptide consisting of 84 amino acid residues. A hormone is a chemical messenger of the body, produced and secreted by special glands called exocrine glands. It is released directly into the bloodstream and travels to its target cells, often distant, where it binds to a structure called a receptor, that is found either inside or on the surface of the target cells. Receptors bind a specific hormone and the result is a specific physiologic response, meaning a normal response of the body. The activity of all the hormones or growth factors secreted by endocrine glands and circulating in blood is controlled by the exocrine system of the body. PTH finds its major target cells in bone, kidneys , and the gastrointestinal system.

Function

The function of the parathyroid glands is to secrete parathyroid hormone, which causes the release of the calcium present in bone to extracellular fluid (ECF). The ECF is the fluid found outside cells in all body tissues. PTH does this by activating the production of osteoblasts, special cells of the body involved in the production of bone and slowing down osteoclasts, other specialized cells involved in the removal of bone.

Calcitonin, a hormone produced by the thyroid gland that also regulates ECF calcium levels and serves to counteract the calcium-producing effects of PTH. The adult body contains as much as 1 kg of calcium. Most of this calcium is found in bone and teeth, and less than 1 g is found in the ECF, with 50% in the form of ionized calcium (Ca²⁺). Both calcitonin and PTH respond to the circulating levels of Ca²⁺. An increased amount of ECF Ca²⁺ leads to an increased release of calcitonin and a decreased PTH release; similarly, a decreased amount of ECF Ca²⁺ results in a decreased release of calcitonin and an increased PTH release. Overall, calcitonin acts quickly to reduce ECF Ca²⁺ levels, while PTH works more slowly to ensure that adequate Ca²⁺ ECF levels are maintained. PTH action is thus opposed to that of calcitonin.

Three major calcium regulatory processes are affected by PTH:

• Release of calcium from bone: Although the mechanisms remain unclear, it is known that PTH stimulates bone tissue to release calcium into blood.
• Increased calcium absorption in the intestine: Facilitating calcium absorption from the small intestine increases calcium amounts in the blood. PTH also stimulates this process, but indirectly, meaning that it stimulates production of vitamin D in the kidney. Vitamin D in turn facilitates the production of a protein in intestinal cells that binds calcium for its efficient absorption into the blood.
• Suppression of calcium loss in urine: Additionally, PTH slows down the elimination of calcium in urine, thus maintaining calcium levels in blood.

KEY TERMS

Amino acid —A class of organic molecules containing mostly the elements carbon, nitrogen, and oxygen, and that combine in linear chains to form polypeptides and proteins. There are 20 naturally-occurring amino acids: alanine, arginine, aspargine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.

Antagonist —A substance that cancels or counteracts the action of another.

Bone —The hard tissue of the skeleton. Bones mostly consist of calcium carbonate, calcium phosphate, and gelatine.

Bone mineral density —Proper degree of hardness in bones. It is regulated by remodeling, a process that occurs 24 hours a day, seven days a week and involves the continuous breakdown and re-formation of bone.

Calcitonin —A polypeptide hormone produced by the thyroid gland that causes a reduction of calcium levels in the blood. Counteracts PTH.

Endocrine glands —Glands that secrete substances that are released directly into the blood stream and that regulate metabolism and other body functions.

Endocrine system —The system of glands in the body that secrete their hormones directly into the circulatory system.

Extracellular fluid (ECF) —The fluid found outside of the cells and between the cells in body tissues.

Hormone —A naturally occurring substance secreted by specialized cells that affects the metabolism or behavior of other cells possessing receptors for the hormone. Thus, hormones acts like chemical messengers and bind to receptors on target cells.

Metabolism —The sum of all the physical and chemical reactions required to maintain the function of body systems and organs.

Osteoblasts —Cells that are associated with the production of bone as they mature.

Osteoclasts —A large cell with many nuclei associated with the absorption and removal of bone.

Parathyroid hormone (PTH) —Polypeptide hormone consisting of 84 amino acid residues that is secreted by the parathyroid glands. PTH is involved in regulating bone metabolism by controlling calcium and phosphorus levels in the body. Counteracts calcitonin.

Physiologic response —Characteristic of, or conforming to the normal functioning of the body or a tissue or organ.

Receptor —A cell structure, inside or on the surface of cells, that binds a specific hormone and starts a specific physiologic response.

Thyroid gland —A butterfly-shaped endocrine gland located in the neck on both sides of the windpipe. It secretes the hormone thyroxine which controls the rate of metabolism.

Role in human health

The regulation of ECF calcium levels by PTH is the key for essential body functions such as the transmission of impulses across nerve junctions (synapses), muscle contraction , and blood coagulation , processes that all require calcium. Calcium imbalance will therefore result in serious adverse health effects.

Another major effect of the calcium regulatory activity of PTH is to play a significant role in bone formation and bone maintenance. Bones are hard because they contain calcium compounds, such as calcium carbonate and calcium phosphate. Thus, they provide a frame to the body for physical support as well as for protection. They also store calcium and phosphorus reserves, the chemicals required for bone growth. Bone formation, or the development of bone mineral density is usually complete around 25–28 years of age. Since bone is a live tissue, just like the other organs of the body, such as the heart and kidneys, it maintains its optimal degree of hardness by a very active process, called remodeling. Remodeling occurs 24 hours a day, seven days a week. It involves the continuous breakdown and re-formation of bone to repair any damage that may occur, such as fractures , and to maintain the proper levels of calcium in the bone cells.

When the amount of calcium in the ECF falls below normal as a result of the bone remodeling process absorbing it inside the bone cells, the release of PTH then brings it back within the normal range. As calcium amounts increase, the amount of phosphate in blood is also reduced.

Common diseases and disorders

• Primary hyperparathyroidism. The most common disease of parathyroid glands is overactivity, meaning that too much PTH is being produced. Hyperparathyroidism is the result of parathyroid gland disease, which then secretes the hormone in abnormally high amounts. Common symptoms of this disorder are chronic increases of calcium amounts in the blood (hypercalcemia), kidney stones , and decalcification of bone. The major symptom of this condition is decalcification of bone, leading to brittle bones that fracture easily (rubber bones).
• Secondary hyperparathyroidism. In this form of hyperparathyroidism, the condition is due to a disease not directly affecting the parathyroid glands that leads to high levels of PTH. Kidney disease is often associated with this disorder because it reduces the renal excretion of phospate, causing increased phosphate levels in the blood which then decrease the level of free ionized calcium. In addition, most of the calcium in extracellular fluid is not in the ionized form. Rather, at least 50% of the extracellular fluid calcium is in the non-ionized form bound to proteins and phosphate. Secondary hyperparathyroidism is also due to a poor diet, deficient in calcium or vitamin D, or which is high in phosphorus (found in meat).
• Hypoparathyroidism. Hypoparathyroidism results from inadequate PTH production. It is a rare condition, most commonly caused by damage or removal of the parathyroid glands at the time of parathyroid or thyroid surgery. Typically, it results in decreased concentrations of calcium and increased concentrations of phosphorus in blood. The resulting hypocalcemia often leads to convulsions, and can be life-threatening.
• Parathyroid adenoma. Parathyroid adenoma commonly occurs on only one of the four parathyroids. The condition accounts for 87–93% of all patients diagnosed with primary hyperparathyroidism. The enlarged parathyroid that has the tumor usually secretes all the PTH with the other three glands responding to the high calcium levels caused by the overactive one by becoming dormant. Parathyroid adenoma is very rarely cancerous (less than one in 500), but it slowly damages the body by causing abnormally high level of calcium in the blood.
• Secondary osteoporosis . This bone disorder results from a slight excess of bone removal over bone formation, often the result of prolonged hyperthyroidism.
• Congenital hypoparathyroidism. Individuals with this condition are born without parathyroid tissues. It is due to a genetic disorder resulting in abnormal genes that either encode for abnormal forms of PTH or its receptor, or prevent normal parathyroid gland development before birth.

Resources

BOOKS

Bilezikian, John P., Robert Marcus, and Michael Levine, eds. The Parathyroids, Second edition. New York: Academic Press, 2001.

Whitfield, James F., Paul Morley, and Gordon E. Willick. The Parathyroid Hormone: An Unexpected Bone Builder for Treating Osteoporosis. Georgetown: Landes Bioscience, 1998.

PERIODICALS

Angeletti, R. H., T. D'Amico, and J. Russell, "Regulation of parathyroid secretion. Chromogranins, chemokines, and calcium." Advances in Experimental and Medical Biology 482 (2000): 217–223.

Goltzman, D., and J. H. White, "Developmental and tissue-specific regulation of parathyroid hormone." Critical Reviews in Eukaryotic Gene Expression 10 (2000): 135–49.

Mihai, R., and J. R. Farndon. "Parathyroid disease and calcium metabolism." British Journal of Anaesthesiology 85 (July 2000): 29–43.

Strewler, G. J. "Medical approaches to primary hyperparathyroidism." Endocrinology & Metabolism, Clin. North Am. 29 (September 2000): 523–529.

Weigel, R. J. "Nonoperative management of hyperparathyroidism: present and future." Current Opinions in Oncology 13 (January 2001): 33–38.

Whitfield, J., P. Morley, and G. Willick, "The parathyroid hormone, its fragments and analogues-potent bone-builders for treating osteoporosis." Expert Opinions in Investigative Drugs 9 (June 2000): 1293–1315.

OTHER

"Hyperparathyroidism." Endocrine Disorders and Endocrine Surgery Webpage. <http://www.endocrineweb.com/hyperpara.html>.

Monique Laberge, Ph.D.

Parathyroid Glands

Definition

The four parathyroid glands are small, light-colored lumps protruding from the surface of the thyroid gland. They secrete parathyroid hormone, the most important regulator of calcium and phosphorus amounts in the body.

Description

The parathyroid glands are located on the thyroid gland, a butterfly-shaped gland found in the neck on both sides of the windpipe. There are then two parathyroid glands on each side of the neck for a total of four. Parathyroid tissue consists of two major cell types: oxyphil cells, whose function is unknown, and chief cells, which produce parathyroid hormone. The structure of a parathyroid gland is very different from that of a thyroid gland. The chief cells that produce parathyroid hormone are arranged in tightly-packed nests around small blood vessels, quite unlike the thyroid cells that produce thyroid hormones, which are arranged in spheres (thyroid follicles).

The parathyroid glands secrete parathyroid hormone (PTH), a polypeptide consisting of 84 amino acid residues. A hormone is a chemical messenger of the body, produced and secreted by special glands called exocrine glands. It is released directly into the bloodstream and travels to its target cells, often distant, where it binds to a structure called a receptor, that is found either inside or on the surface of the target cells. Receptors bind a specific hormone and the result is a specific physiologic response, meaning a normal response of the body. The activity of all the hormones or growth factors secreted by endocrine glands and circulating in blood is controlled by the exocrine system of the body. PTH finds its major target cells in bone, kidneys, and the gastrointestinal system.

Function

The function of the parathyroid glands is to secrete parathyroid hormone, which causes the release of the calcium present in bone to extracellular fluid (ECF). The ECF is the fluid found outside cells in all body tissues. PTH does this by activating the production of osteoblasts, special cells of the body involved in the production of bone and slowing down osteoclasts, other specialized cells involved in the removal of bone.

Calcitonin, a hormone produced by the thyroid gland that also regulates ECF calcium levels and serves to counteract the calcium-producing effects of PTH. The adult body contains as much as 1 kg of calcium. Most of this calcium is found in bone and teeth, and less than 1 g is found in the ECF, with 50% in the form of ionized calcium (Ca²⁺). Both calcitonin and PTH respond to the circulating levels of Ca²⁺. An increased amount of ECF Ca²⁺ leads to an increased release of calcitonin and a decreased PTH release; similarly, a decreased amount of ECF Ca²⁺ results in a decreased release of calcitonin and an increased PTH release. Overall, calcitonin acts quickly to reduce ECF Ca²⁺ levels, while PTH works more slowly to ensure that adequate Ca²⁺ ECF levels are maintained. PTH action is thus opposed to that of calcitonin.

Three major calcium regulatory processes are affected by PTH:

• Release of calcium from bone: Although the mechanisms remain unclear, it is known that PTH stimulates bone tissue to release calcium into blood.
• Increased calcium absorption in the intestine: Facilitating calcium absorption from the small intestine increases calcium amounts in the blood. PTH also stimulates this process, but indirectly, meaning that it stimulates production of vitamin D in the kidney. Vitamin D in turn facilitates the production of a protein in intestinal cells that binds calcium for its efficient absorption into the blood.
• Suppression of calcium loss in urine: Additionally, PTH slows down the elimination of calcium in urine, thus maintaining calcium levels in blood.

Role in human health

The regulation of ECF calcium levels by PTH is the key for essential body functions such as the transmission of impulses across nerve junctions (synapses), muscle contraction, and blood coagulation, processes that all require calcium. Calcium imbalance will therefore result in serious adverse health effects.

Another major effect of the calcium regulatory activity of PTH is to play a significant role in bone formation and bone maintenance. Bones are hard because they contain calcium compounds, such as calcium carbonate and calcium phosphate. Thus, they provide a frame to the body for physical support as well as for protection. They also store calcium and phosphorus reserves, the chemicals required for bone growth. Bone formation, or the development of bone mineral density is usually complete around 25-28 years of age. Since bone is a live tissue, just like the other organs of the body, such as the heart and kidneys, it maintains its optimal degree of hardness by a very active process, called remodeling. Remodeling occurs 24 hours a day, seven days a week. It involves the continuous breakdown and re-formation of bone to repair any damage that may occur, such as fractures, and to maintain the proper levels of calcium in the bone cells.

When the amount of calcium in the ECF falls below normal as a result of the bone remodeling process absorbing it inside the bone cells, the release of PTH then brings it back within the normal range. As calcium amounts increase, the amount of phosphate in blood is also reduced.

KEY TERMS

Amino acid— A class of organic molecules containing mostly the elements carbon, nitrogen and oxygen, and that combine in linear chains to form polypeptides and proteins. There are 20 naturally-occurring amino acids: alanine, arginine, aspargine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.

Antagonist— A substance that cancels or counteracts the action of another.

Bone— The hard tissue of the skeleton. Bones mostly consist of calcium carbonate, calcium phosphate, and gelatine.

Bone mineral density— Proper degree of hardness in bones. It is regulated by remodeling, a process that occurs 24 hours a day, seven days a week and involves the continuous breakdown and re-formation of bone.

Calcitonin— A polypeptide hormone produced by the thyroid gland that causes a reduction of calcium levels in the blood. Counteracts PTH.

Endocrine glands— Glands that secrete substances that are released directly into the blood stream and that regulate metabolism and other body functions.

Endocrine system— The system of glands in the body that secrete their hormones directly into the circulatory system.

Extracellular fluid (ECF)— The fluid found outside of the cells and between the cells in body tissues.

Hormone— A naturally occurring substance secreted by specialized cells that affects the metabolism or behavior of other cells possessing receptors for the hormone. Thus, hormones acts like chemical messengers and bind to receptors on target cells.

Metabolism— The sum of all the physical and chemical reactions required to maintain the function of body systems and organs.

Osteoblasts— Cells that are associated with the production of bone as they mature.

Osteoclasts— A large cell with many nuclei associated with the absorption and removal of bone.

Parathyroid hormone (PTH)— Polypeptide hormone consisting of 84 amino acid residues that is secreted by the parathyroid glands. PTH is involved in regulating bone metabolism by controlling calcium and phosphorus levels in the body. Counteracts calcitonin.

Physiologic response— Characteristic of, or conforming to the normal functioning of the body or a tissue or organ.

Receptor— A cell structure, inside or on the surface of cells, that binds a specific hormone and starts a specific physiologic response.

Thyroid gland— A butterfly-shaped endocrine gland located in the neck on both sides of the windpipe. It secretes the hormone thyroxine which controls the rate of metabolism.

Common diseases and disorders

• Primary hyperparathyroidism. The most common disease of parathyroid glands is overactivity, meaning that too much PTH is being produced. Hyperparathyroidism is the result of parathyroid gland disease, which then secretes the hormone in abnormally high amounts. Common symptoms of this disorder are chronic increases of calcium amounts in the blood (hypercalcemia), kidney stones, and decalcification of bone. The major symptom of this condition is decalcification of bone, leading to brittle bones that fracture easily (rubber bones).
• Secondary hyperparathyroidism. In this form of hyperparathyroidism, the condition is due to a disease not directly affecting the parathyroid glands that leads to high levels of PTH. Kidney disease is often associated with this disorder because it reduces the renal excretion of phosphate, causing increased phosphate levels in the blood which then decrease the level of free ionized calcium. In addition, most of the calcium in extracellular fluid is not in the ionized form. Rather, at least 50% of the extracellular fluid calcium is in the non-ionized form bound to proteins and phosphate. Secondary hyperparathyroidism is also due to a poor diet, deficient in calcium or vitamin D, or which is high in phosphorus (found in meat).
• Hypoparathyroidism. Hypoparathyroidism results from inadequate PTH production. It is a rare condition, most commonly caused by damage or removal of the parathyroid glands at the time of parathyroid or thyroid surgery. Typically, it results in decreased concentrations of calcium and increased concentrations of phosphorus in blood. The resulting hypocalcemia often leads to convulsions, and can be life-threatening.
• Parathyroid adenoma. Parathyroid adenoma commonly occurs on only one of the four parathyroids. The condition accounts for 87-93% of all patients diagnosed with primary hyperparathyroidism. The enlarged parathyroid that has the tumor usually secretes all the PTH with the other three glands responding to the high calcium levels caused by the overactive one by becoming dormant. Parathyroid adenoma is very rarely cancerous (less than one in 500), but it slowly damages the body by causing abnormally high level of calcium in the blood.
• Secondary osteoporosis. This bone disorder results from a slight excess of bone removal over bone formation, often the result of prolonged hyperthyroidism.
• Congenital hypoparathyroidism. Individuals with this condition are born without parathyroid tissues. It is due to a genetic disorder resulting in abnormal genes that either encode for abnormal forms of PTH or its receptor, or prevent normal parathyroid gland development before birth.

Resources

BOOKS

Bilezikian, John P., Robert Marcus, and Michael Levine, eds. The Parathyroids, Second edition. New York: Academic Press, 2001.

Whitfield, James F., Paul Morley, and Gordon E. Willick. The Parathyroid Hormone: An Unexpected Bone Builder for Treating Osteoporosis. Georgetown: Landes Bioscience, 1998.

PERIODICALS

Angeletti, R. H., T. D'Amico, and J. Russell, "Regulation of parathyroid secretion. Chromogranins, chemokines, and calcium." Advances in Experimental and Medical Biology 482 (2000): 217-223.

Goltzman, D., and J. H. White, "Developmental and tissue-specific regulation of parathyroid hormone." Critical Reviews in Eukaryotic Gene Expression 10 (2000): 135-49.

Mihai, R., Farndon, J. R. "Parathyroid disease and calcium metabolism." British Journal of Anaesthesiology 85 (July 2000): 29-43.

Strewler, G. J. "Medical approaches to primary hyperparathyroidism." Endocrinology & Metabolism, Clin. North Am. 29 (September 2000): 523-529.

Weigel, R. J. "Nonoperative management of hyperparathyroidism: present and future." Current Opinions in Oncology 13 (January 2001): 33-38.

Whitfield, J., P. Morley, and G. Willick, "The parathyroid hormone, its fragments and analogues-potent bone-builders for treating osteoporosis." Expert Opinions in Investigative Drugs 9 (June 2000): 1293-1315.

OTHER

"Hyperparathyroidism." Endocrine Disorders and Endocrine Surgery Webpage. 〈http://www.endocrineweb.com/hyperpara.html〉.

parathyroid glands These small but vitally necessary groups of cells, usually four of them, lie on the back of the thyroid gland in the neck. They are endocrine glands — meaning that they deliver their secretion directly into the passing blood. The peptide parathyroid hormone (or parathormone) will therefore reach the whole of the rest of the body, but attaches only to those cells which have receptors for it. The activities which it then modifies in these ‘target’ cells all work towards an increase in the concentration of calcium ions in the extracellular fluid compartment of the body — the blood plasma and the tissue (interstitial) fluid. It is necessary for a great variety of physiological functions — indeed for virtually all of them — that this concentration remains within quite narrow limits.

Where and how, then, would a hormone need to act in order to promote the addition of calcium into the body pool?(i) Calcium from food is absorbed from the intestine: parathyroid hormone promotes conversion of Vitamin D to its active form; this in turn enhances intestinal absorption of calcium.(ii) Calcium is stored in bone mineral: parathyroid hormone stimulates resorption from bone into the blood by activating the osteo-clasts, which break down bone and mobilize the minerals from it.(iii) When the blood passes through the kidneys some of its calcium ions escape into the urine: parathyroid hormone enhances reabsorption by acting on the renal tubule cells.

An appropriate concentration of calcium ions in body fluids is necessary for every transfer of a stimulus from nerve to muscle, and for the contraction of muscle of all types, including the beating of the heart and the regulation of the diameter of blood vessels. The translocation of calcium in and out of cells, and in and out of storage by chemical binding within cells, is also crucial for the secretory activity of glandular cells, producing both external and internal secretions — sweat, milk, saliva, insulin, cortisol, and all the rest, including parathyroid hormone itself.

The parathyroid glands ‘know’ how much hormone to secrete, because their activity is regulated by the concentration of ionized calcium in the blood that flows through them: a rise in calcium inhibits secretion of the hormone and vice versa (a negative feedback mechanism).

Parathyroid hormone thus keeps calcium concentration up — otherwise known as a hypercalcaemic effect. There is also another hormone keeping calcium down: calcitonin, secreted by the ‘C-cells’ within the thyroid gland.

Parathyroid deficiency is rare; it can occur acutely if the glands are inadvertently removed along with the thyroid or with cancerous neck glands. Rarely also, a parathyroid tumour can cause excess of the hormone, resulting in decalcification and cysts in the bones, and kidney problems due to the high concentration of calcium in the filtered blood.

Sheila Jennett

parathyroid glands Four small endocrine glands, usually embedded in the back of the thyroid gland, that secrete a hormone to control the level of calcium and phosphorus in the blood. Overproduction of parathyroid hormone causes loss of calcium from the bones to the blood; a deficiency causes tetany (involuntary muscle spasm). See also endocrine system

parathyroid glands Two pairs of endocrine glands situated behind, or embedded within, the thyroid gland in higher vertebrates. They produce parathyroid hormone, which controls the amount of calcium in the blood. See also C cell.