Parathyroid glands are small

endocrine gland Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, ...

s in the neck of humans and other

tetrapod Tetrapods (; ) are four-limbed vertebrate animals constituting the superclass Tetrapoda (). It includes extant and extinct amphibians, sauropsids ( reptiles, including dinosaurs and therefore birds) and synapsids ( pelycosaurs, extinct t ...

s. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes

parathyroid hormone Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine. PTH influences bone ...

in response to a low blood calcium, which plays a key role in regulating the amount of calcium in the blood and within the bones. Parathyroid glands share a similar blood supply, venous drainage, and lymphatic drainage to the thyroid glands. Parathyroid glands are derived from the

epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...

lining of the third and fourth pharyngeal pouches, with the superior glands arising from the fourth pouch and the inferior glands arising from the higher third pouch. The relative position of the inferior and superior glands, which are named according to their final location, changes because of the migration of embryological tissues.

Hyperparathyroidism Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands (primary hyperparathyroidism) or as response to external stimuli (secondary hyperparathyroidism). ...

and

hypoparathyroidism Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary m ...

, characterized by alterations in the blood calcium levels and bone metabolism, are states of either surplus or deficient parathyroid function.

Structure

The parathyroid glands are two pairs of glands usually positioned behind the left and right lobes of the

thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...

. Each gland is a yellowish-brown flat ovoid that resembles a

lentil The lentil (''Lens culinaris'' or ''Lens esculenta'') is an edible legume. It is an annual plant known for its lens-shaped seeds. It is about tall, and the seeds grow in pods, usually with two seeds in each. As a food crop, the largest pro ...

seed, usually about 6 mm long and 3 to 4 mm wide, and 1 to 2 mm anteroposteriorly. There are typically four parathyroid glands. The two parathyroid glands on each side which are positioned higher are called the superior parathyroid glands, while the lower two are called the inferior parathyroid glands. Healthy parathyroid glands generally weigh about 30 mg in men and 35 mg in women. These glands are not visible or able to be felt during examination of the neck.Illustrated Anatomy of the Head and Neck, Fehrenbach and Herring, Elsevier, 2012, p. 159 Each parathyroid vein drains into the superior, middle and inferior thyroid veins. The superior and middle thyroid veins drain into the

internal jugular vein The internal jugular vein is a paired jugular vein that collects blood from the brain and the superficial parts of the face and neck. This vein runs in the carotid sheath with the common carotid artery and vagus nerve. It begins in the poste ...

, and the inferior thyroid vein drains into the

brachiocephalic vein The left and right brachiocephalic veins (previously called innominate veins) are major veins in the upper chest, formed by the union of each corresponding internal jugular vein and subclavian vein. This is at the level of the sternoclavicular j ...

Lymphatic drainage

Lymphatic vessels from the parathyroid glands drain into

deep cervical lymph node The deep cervical lymph nodes are a group of cervical lymph nodes found near the internal jugular vein in the neck. Structure The deep cervical lymph nodes can be divided into upper and lower groups, or superior and inferior groups. Alternati ...

s and

paratracheal lymph nodes The right and left paratracheal lymph nodes (or paratracheal chains) are groups of lymph nodes located in the throat In vertebrate anatomy, the throat is the front part of the neck, internally positioned in front of the vertebrae. It contains t ...

Variation

The parathyroid glands are variable in number: three or more small glands, and can usually be located on the posterior surface of the thyroid gland. Occasionally, some individuals may have six, eight, or even more parathyroid glands. Rarely, the parathyroid glands may be within the thyroid gland itself, the chest, or even the

thymus The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...

Microanatomy

The parathyroid glands are named for their proximity to the thyroid—and serve a completely different role than the thyroid gland. The parathyroid glands are quite easily recognizable from the thyroid as they have densely packed cells, in contrast with the follicular structure of the

. Two unique types of cells are present in the parathyroid gland: *

Chief cells In human anatomy, there are three types of chief cells, the gastric chief cell, the parathyroid chief cell, and the type 1 chief cells found in the carotid body. Cell types The gastric chief cell (also known as a zymogenic cell or peptic cell) is a ...

, which synthesize and release parathyroid hormone. These cells are small, and appear dark when loaded with parathyroid hormone, and clear when the hormone has been secreted, or in their resting state. * Oxyphil cells, which are lighter in appearance and increase in number with age, have an unknown function. File:Parathyroid gland intermed mag.jpg, Intermediate magnification

micrograph A micrograph or photomicrograph is a photograph or digital image taken through a microscope or similar device to show a magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken on a m ...

H&E stain Hematoxylin and eosin stain ( or haematoxylin and eosin stain or hematoxylin-eosin stain; often abbreviated as H&E stain or HE stain) is one of the principal tissue stains used in histology. It is the most widely used stain in medical diagnos ...

. The white round structures are

fat cell Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...

Adipose tissue Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular ...

comprises 25–40% of normal parathyroid gland tissue. File:Parathyroid oxyphil and chief cells - annotated.jpg, High magnification

. The small, dark cells are

chief cells In human anatomy, there are three types of chief cells, the gastric chief cell, the parathyroid chief cell, and the type 1 chief cells found in the carotid body. Cell types The gastric chief cell (also known as a zymogenic cell or peptic cell) is a ...

, which are responsible for secreting

. The cells with orange/pink staining cytoplasm are oxyphil cells

Development

In the

early development Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal devel ...

of the human embryo, a series of five

pharyngeal arch The pharyngeal arches, also known as visceral arches'','' are structures seen in the embryonic development of vertebrates that are recognisable precursors for many structures. In fish, the arches are known as the branchial arches, or gill arche ...

es and four pharyngeal pouches form that give rise to the face, neck, and surrounding structures. The pouches are numbered such that the first pouch is the closest to the top of the embryo's head and the fourth is the furthest from it. The parathyroid glands originate from the interaction of the endoderm of the third and fourth pouch and

neural crest Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...

mesenchyme. The position of the glands reverses during embryological development. The pair of glands which is ultimately inferior develops from the third pouch with the

, whereas the pair of glands which is ultimately superior develops from the fourth pouch. During embryological development, the thymus migrates downwards, dragging the inferior glands with it. The superior pair are not dragged downwards by the fourth pouch to the same degree. The glands are named after their final, not embryological, positions. Since the thymus's ultimate destination is in the mediastinum of the chest, it is occasionally possible to have ectopic parathyroids derived from the third pouch within the chest cavity if they fail to detach in the neck. Parathyroid development is regulated by a number of

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

s, including those coding for several

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...

Function

The major function of the parathyroid glands is to maintain the body's

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

and

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...

levels within a very narrow range, so that the nervous and

muscular system The muscular system is an organ system consisting of skeletal, smooth, and cardiac muscle. It permits movement of the body, maintains posture, and circulates blood throughout the body. The muscular systems in vertebrates are controlled through t ...

s can function properly. The parathyroid glands do this by secreting

(PTH). Parathyroid hormone (also known as parathormone) is a small

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that takes part in the control of calcium and phosphate

homeostasis In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...

, as well as bone physiology. Parathyroid hormone has effects antagonistic to those of

calcitonin Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing th ...

. *

Calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

. PTH increases blood calcium levels by directly stimulating osteoblasts and thereby indirectly stimulating

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...

s (through RANK/RANKL mechanism) to break down bone and release calcium. PTH increases gastrointestinal calcium absorption by activating

vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...

, and promotes calcium conservation (reabsorption) by the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...

s. *

Phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...

. PTH is the major regulator of serum phosphate concentrations via actions on the kidney. It is an inhibitor of proximal tubular reabsorption of phosphorus. Through activation of vitamin D the absorption (intestinal) of Phosphate is increased.

Disorders

Parathyroid disease is conventionally divided into states where the parathyroid is overactive (

hyperparathyroidism Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands (primary hyperparathyroidism) or as response to external stimuli (secondary hyperparathyroidism). ...

), and states where the parathyroid is under- or hypoactive (

). Both states are characterised by their symptoms, which relate to the excess or deficiency of

in the blood.

Hyperparathyroidism

Primary

Hyperparathyroidism is the state in which there is excess parathyroid hormone circulating. This may cause bone pain and tenderness, due to increased bone resorption. Due to increased circulating calcium, there may be other symptoms associated with hypercalcemia, most commonly dehydration. Hyperparathyroidism is most commonly caused by a benign proliferation of chief cells in single gland, and rarely MEN syndrome. This is known as

primary hyperparathyroidism Primary hyperparathyroidism (or PHPT) is a medical condition where the parathyroid gland (or a benign tumor within it) produce excess amounts of parathyroid hormone (PTH). The symptoms of the condition relate to the resulting elevated serum calcium ...

, which is generally managed by surgical removal of the abnormal parathyroid gland.

Secondary

Renal disease may lead to hyperparathyroidism. When too much calcium is lost, there is a compensation by the parathyroid, and parathyroid hormone is released. The glands hypertrophy to synthesise more parathyroid hormone. This is known as

secondary hyperparathyroidism Secondary hyperparathyroidism is the medical condition of excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia (low blood calcium levels), with resultant hyperplasia of these glands. This disorde ...

Tertiary

If this situation exists for a prolonged period of time of secondary hyperparathyroidism, the parathyroid tissue may become unresponsive to the blood calcium levels, and begin to autonomously release parathyroid hormone. This is known as tertiary hyperparathyroidism.

Hypoparathyroidism

The state of decreased parathyroid activity is known as hypoparathyroidism. This is most commonly associated with damage to the glands or their blood supply during thyroid surgeryit may be associated with rarer genetic syndromes such as

DiGeorge syndrome DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facial features, frequent i ...

, which is inherited as an autosomal dominant syndrome. Hypoparathyroidism will occur after surgical removal of the parathyroid glands. Occasionally, an individual's tissues are resistant to the effects of parathyroid hormone. This is known as

pseudohypoparathyroidism Pseudohypoparathyroidism is a condition associated primarily with resistance to the parathyroid hormone. Those with the condition have a low serum calcium and high phosphate, but the parathyroid hormone level (PTH) is appropriately high (due to th ...

. In this case the parathyroid glands are fully functional, and the hormone itself is not able to function, resulting in a decrease in blood calcium levels. Pseudohypoparathyroidism is often associated with the genetic condition Albright's hereditary osteodystrophy. Pseudo-pseudohypoparathyroidism, one of the longest words in the English language, is used to describe an individual with Albright's hereditary osteodystrophy with normal parathyroid hormone and serum calcium levels. Hypoparathyroidism may present with symptoms associated with decreased calcium, and is generally treated with

Vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...

analogues.

History

The parathyroid glands were first discovered in the

Indian Rhinoceros } The Indian rhinoceros (''Rhinoceros unicornis''), also called the Indian rhino, greater one-horned rhinoceros or great Indian rhinoceros, is a rhinoceros species native to the Indian subcontinent. It is listed as Vulnerable on the IUCN Red Li ...

by Richard Owen in 1852. In his description of the neck anatomy, Owen referred to the glands as "a small compact yellow glandular body attached to the thyroid at the point where the veins emerged". The glands were first discovered in humans by Ivar Viktor Sandström (1852–1889), a Swedish medical student, in 1880 at

Uppsala University Uppsala University ( sv, Uppsala universitet) is a public research university in Uppsala, Sweden. Founded in 1477, it is the oldest university in Sweden and the Nordic countries still in operation. The university rose to significance during ...

. Unaware of Owen's description, he described the glands in his monograph "On a New Gland in Man and Fellow Animals" as the "glandulae parathyroidae", noting its existence in dogs, cats, rabbits, oxen, horses and humans. For several years, Sandström's description received little attention. Eugene Gley, Giulio Vassale, and others documented the putative function of the glands in 1891, noting the connection between their removal and the development of muscular

tetany Tetany or tetanic seizure is a medical sign consisting of the involuntary contraction of muscles, which may be caused by disorders that increase the action potential frequency of muscle cells or the nerves that innervate them. Muscle cramps caus ...

. William G. MacCallum in 1908, investigating tumours of the parathyroid, proposed their role in calcium metabolism. He noted that "Tetany occurs spontaneously in many forms and may be produced by the destruction of the parathyroid glands". The first successful removal of the parathyroid may have been carried out in 1928 by medical doctor Isaac Y Olch, whose

intern An internship is a period of work experience offered by an organization for a limited period of time. Once confined to medical graduates, internship is used practice for a wide range of placements in businesses, non-profit organizations and gove ...

had noticed elevated calcium levels in an elderly patient with muscle weakness. Prior to this surgery, patients with removed parathyroid glands typically died from muscular tetany. Parathyroid hormone was isolated in 1923 by Adolph M. Hanson and 1925 by James B. Collip. Studies of parathyroid hormone levels by

Roger Guillemin Roger Charles Louis Guillemin (born January 11, 1924) is a French-American neuroscientist. He received the National Medal of Science in 1976, and the Nobel prize for medicine in 1977 for his work on neurohormones, sharing the prize that year ...

, Andrew Schally and

Rosalyn Sussman Yalow Rosalyn Sussman Yalow (July 19, 1921 – May 30, 2011) was an American medical physicist, and a co-winner of the 1977 Nobel Prize in Physiology or Medicine (together with Roger Guillemin and Andrew Schally) for development of the radioimmunoassay ...

led to the development of

immunoassay An immunoassay (IA) is a biochemical test that measures the presence or concentration of a macromolecule or a small molecule in a solution through the use of an antibody (usually) or an antigen (sometimes). The molecule detected by the immunoass ...

s capable of measuring body substances and a

Nobel Prize The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...

in 1977.

Other animals

Parathyroid glands are found in all adult

s; they vary in their number and position. Mammals typically have four parathyroid glands, while other types of animals typically have six. The removal of parathyroid glands in animals produces a condition resembling acute poisoning with irregular muscle contractions. Fish do not possess parathyroid glands; several species have been found to express parathyroid hormone. Developmental genes and calcium-sensing receptors in fish gills are similar to those within the parathyroid glands of birds and mammals. It has been suggested that the tetrapod glands may have been evolutionarily derived from these fish gills.

Additional images

File:Gross pathology of parathyroid gland, annotated.jpg, Gross pathology of a parathyroid gland (white arrow), next to the thyroid gland Image:Gray1175.png, Scheme showing development of branchial epithelial bodies. I, II, III, IV.

Branchial pouches In the embryonic development of vertebrates, pharyngeal pouches form on the endodermal side between the pharyngeal arches. The pharyngeal grooves (or clefts) form the lateral ectodermal surface of the neck region to separate the arches. The pou ...

Notes

References

External links

Endocrine Web: ParathyroidUniversity of Iowa Hospitals & Clinics: Parathyroid
{{Authority control Glands