Parathyroid glands are small

endocrine gland The endocrine system is a network of glands and organs located throughout the body. Along with the nervous system, it makes the neuroendocrine system, which controls and regulates many of the body's functions. Endocrine glands are ductless gland ...

s in the neck of humans and other

tetrapod A tetrapod (; from Ancient Greek :wiktionary:τετρα-#Ancient Greek, τετρα- ''(tetra-)'' 'four' and :wiktionary:πούς#Ancient Greek, πούς ''(poús)'' 'foot') is any four-Limb (anatomy), limbed vertebrate animal of the clade Tetr ...

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 a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...

in variable locations. The parathyroid gland produces and secretes parathyroid hormone in response to 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 a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

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 hyperparathyroi ...

and hypoparathyroidism, 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 a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...

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

lentil The lentil (''Vicia lens'' or ''Lens culinaris'') is an annual plant, annual legume grown for its Lens (geometry), lens-shaped edible seeds or ''pulses'', also called ''lentils''. It is about tall, and the seeds grow in Legume, pods, usually w ...

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 posteri ...

, 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 Thorax, upper chest, formed by the union of the ipsilateral internal jugular vein and subclavian vein (the so-called venous angle) behind the ster ...

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 (: thymuses or thymi) is a specialized primary lymphoid organ of the immune system. Within the thymus, T cells mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. The thymus ...

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 is an image, captured photographically or digitally, taken through a microscope or similar device to show a magnify, magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken ...

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 cells.

Adipose tissue Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...

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 of the human

embryo An embryo ( ) is the initial stage of development for 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 sp ...

, a series of five

pharyngeal arch The pharyngeal arches, also known as visceral arches'','' are transient structures seen in the Animal embryonic development, embryonic development of humans and other vertebrates, that are recognisable precursors for many structures. In fish, t ...

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 farthest 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 gastr ...

of the third and fourth pouch and

neural crest The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, ...

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 ever ...

. 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 downward, dragging the inferior glands with it. The superior pair are not dragged downward 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 has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

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 (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

Function

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

calcium Calcium is a chemical element; it has 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 to it ...

and

phosphate Phosphates are the naturally occurring form of the element phosphorus. 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 orthop ...

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

muscular system The muscular system is an organ (anatomy), organ system consisting of skeletal muscle, skeletal, smooth muscle, smooth, and cardiac muscle, cardiac muscle. It permits movement of the body, maintains posture, and circulates blood throughout the bo ...

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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that takes part in the control of calcium and phosphate

homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...

, 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; it has 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 to it ...

. 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 bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...

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 structurally related, fat-soluble compounds responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most important compo ...

, and promotes calcium conservation (reabsorption) by the

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

s. *

Phosphate Phosphates are the naturally occurring form of the element phosphorus. 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 orthop ...

. 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 hyperparathyroi ...

), and states where the parathyroid is under- or hypoactive ( hypoparathyroidism). 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 in the blood. This may cause bone pain and tenderness, due to increased

bone resorption Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. The osteoclasts are multi-nuclea ...

. With 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 one parathyroid gland, and rarely in MEN syndrome. This is known as primary hyperparathyroidism, 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 from the blood via urination, there is a compensation by the parathyroid, and parathyroid hormone is released. The glands enlarge (hypertrophy) to synthesize more parathyroid hormone. This is known as secondary hyperparathyroidism.

Tertiary

If secondary hyperparathyroidism persists over months, 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 ...

, 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 Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

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. 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 structurally related, fat-soluble compounds responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most important compo ...

analogues.

History

The parathyroid glands were first discovered in the

Indian rhinoceros The Indian rhinoceros (''Rhinoceros unicornis''), also known as the greater one-horned rhinoceros, great Indian rhinoceros or Indian rhino, is a species of rhinoceros found in the Indian subcontinent. It is the second largest living rhinocer ...

Richard Owen Sir Richard Owen (20 July 1804 – 18 December 1892) was an English biologist, comparative anatomy, comparative anatomist and paleontology, palaeontologist. Owen is generally considered to have been an outstanding naturalist with a remarkabl ...

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 (UU) () is a public university, public research university in Uppsala, Sweden. Founded in 1477, it is the List of universities in Sweden, oldest university in Sweden and the Nordic countries still in operation. Initially fou ...

. Unaware of Owen's description, he described the glands in his

monograph A monograph is generally a long-form work on one (usually scholarly) subject, or one aspect of a subject, typically created by a single author or artist (or, sometimes, by two or more authors). Traditionally it is in written form and published a ...

"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. 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 to practice for a wide range of placements in businesses, non-profit organizations and g ...

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 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 immunoassay ...

s capable of measuring body substances and a

Nobel Prize The Nobel Prizes ( ; ; ) are awards administered by the Nobel Foundation and granted in accordance with the principle of "for the greatest benefit to humankind". The prizes were first awarded in 1901, marking the fifth anniversary of Alfred N ...

in 1977.

Other animals

Parathyroid glands are found in all adult

s; they vary in their number and position.

Mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

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 Endocrine system anatomy Glands