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, thy ...

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 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 ...

in variable locations. The parathyroid gland produces and secretes parathyroid hormone 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 intercellu ...

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 Bone remodeling (or bone metabolism) is a lifelong process where mature bone tissue is removed from the skeleton (a process called ''bone resorption'') and new bone tissue is formed (a process called '' ossification'' or ''new bone formation''). ...

, 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 ...

. 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 p ...

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 ...

Lymphatic drainage

Lymphatic vessels from the parathyroid glands drain into deep cervical lymph nodes and paratracheal lymph nodes.

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, 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 diag ...

. 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, which are responsible for secreting parathyroid hormone. 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 An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

, 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 Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gast ...

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 Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every ...

. 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 Superior may refer to: *Superior (hierarchy), something which is higher in a hierarchical structure of any kind Places *Superior (proposed U.S. state), an unsuccessful proposal for the Upper Peninsula of Michigan to form a separate state *Lake ...

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 ...

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 parathyroid hormone (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 the ...

. *

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 ...

. PTH increases blood calcium levels by directly stimulating osteoblasts and thereby indirectly stimulating osteoclasts (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 Lipophilicity, 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 ar ...

, 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 parathyroid hormone 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 Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcem ...

, 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 diso ...

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 Tertiary hyperparathyroidism is a condition involving the overproduction of the hormone, parathyroid hormone, produced by the parathyroid glands. The parathyroid glands are involved in monitoring and regulating blood calcium levels and respond by ...

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, which is inherited as an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

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. 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 Albright's hereditary osteodystrophy is a form of osteodystrophy, and is classified as the phenotype of pseudohypoparathyroidism type 1A; this is a condition in which the body does not respond to parathyroid hormone. Signs and symptoms The dis ...

. 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 Lipophilicity, 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 ar ...

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 ...

Richard Owen Sir Richard Owen (20 July 1804 – 18 December 1892) was an English biologist, comparative anatomist and paleontologist. Owen is generally considered to have been an outstanding naturalist with a remarkable gift for interpreting fossils. Ow ...

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 A monograph is a specialist work of writing (in contrast to reference works) or exhibition on a single subject or an aspect of a subject, often by a single author or artist, and usually on a scholarly subject. In library cataloging, ''monogra ...

"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 cau ...

. 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,

Andrew Schally Andrzej Viktor "Andrew" Schally (born 30 November 1926) is an American endocrinologistAndrew V. Schally"Andrew V. Schally" ''Encyclopædia Britannica''. of Polish ancestry, who was a corecipient, with Roger Guillemin and Rosalyn Sussman Yalow, of ...

and Rosalyn Sussman Yalow 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 immunoa ...

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.

Mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur ...

s 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.

Notes

References

External links

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