Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. 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 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 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.
Thyroid and parathyroids as viewed from the back of the neck
|Precursor||neural crest mesenchyme and third and fourth pharyngeal pouch endoderm|
|Artery||superior thyroid artery, inferior thyroid artery,|
|Vein||superior thyroid vein, middle thyroid vein, inferior thyroid vein,|
|Nerve||middle cervical ganglion, inferior cervical ganglion|
|Lymph||pretracheal, prelaryngeal, jugulodigastric lymph nodes|
|Latin||glandula parathyreoidea inferior, glandula parathyreoidea superior|
The parathyroid glands are two pairs of glands usually positioned behind the left and right lobes of the thyroid. Each gland is a yellowish-brown flat ovoid that resembles a lentil 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.
Each parathyroid vein drains into the superior, middle and inferior thyroid veins. The superior and middle thyroid veins drain into the internal jugular vein, and the inferior thyroid vein drains into the brachiocephalic vein.
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 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 thyroid. Two unique types of cells are present in the parathyroid gland:
In the early development of the human embryo, a series of five pharyngeal arches 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 mesenchyme. The position of the glands reverses during embryological life. The pair of glands which is ultimately inferior develops from the third pouch with the thymus, 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.
The major function of the parathyroid glands is to maintain the body's calcium and phosphate levels within a very narrow range, so that the nervous and muscular systems can function properly. The parathyroid glands do this by secreting parathyroid hormone (PTH).
Parathyroid hormone (also known as parathormone) is a small protein that takes part in the control of calcium and phosphate homeostasis, as well as bone physiology. Parathyroid hormone has effects antagonistic to those of calcitonin.
Parathyroid disease is conventionally divided into states where the parathyroid is overactive (hyperparathyroidism), 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 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, which is generally managed by surgical removal of the abnormal parathyroid gland.
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.
If this situation exists for a prolonged period of time, the parathyroid tissue may become unresponsive to the blood calcium levels, and begin to autonomously release parathyroid hormone. This is known as tertiary hyperparathyroidism.
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 surgery — it may be associated with rarer genetic syndromes such as DiGeorge syndrome, 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. 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. Pseudopseudohypoparathyroidism, 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.
Parathyroid glands are found in all adult tetrapods; 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.
A calcimimetic is a pharmaceutical drug that mimics the action of calcium on tissues, by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues. Calcimimetics are used to treat secondary hyperparathyroidism (SHPT).In the treatment of SHPT patients on dialysis calcimimetics does not appear to affect the risk of early death. It does decrease the need for a parathyroidectomy but caused more issues with low blood calcium levels and vomiting.Cinacalcet was the first calcimimetic to be approved. Cinacalcet mimics calcium at the parathyroid hormone receptor. This binding will increase the sensitivity of calcium-sensing receptors (CaSR) on the parathyroid gland. As a result of the receptor "thinking" there is sufficient calcium, parathyroid hormone (PTH) secretion will be reduced. Lower calcium levels will be seen as well.
On August 25, 2015 Amgen Inc. announced that it had submitted a new drug application with the United States Food and Drug Administration for a new calcimimetic, etelcalcetide (formerly velcalcetide), for the treatment of SHPT in chronic kidney disease (CKD) patients on hemodialysis. Etcalcetide is administered intravenously thrice weekly at the end of each dialysis session. Etcalcetide binds to the CaSR on the parathyroid gland, which results in receptor activation and ultimately reduction in PTH.
Calcimimetics can be used concomitantly with vitamin D therapy.
Calcimimetic use can have side effects. Common side effects include: nausea and vomiting, hypocalcemia, and adynamic bone disease if intact parathyroid hormone (iPTH) levels drop below 100pg/mL.Calcium-sensing receptor
The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. It is primarily expressed in the parathyroid gland and the renal tubules of the kidney. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone (PTH). In the kidney it has an inhibitory effect on the reabsorption of calcium, potassium, sodium, and water depending on which segment of the tubule is being activated.Chief cell
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.Cranial neural crest
The cranial neural crest is a form of neural crest.The cranial neural crest arises in the anterior and populates the face and the pharyngeal arches giving rise to bones, cartilage, nerves and connective tissue. The endocranium and facial bones of the skull are ultimately derived from crest cells.
Other Migration Locations:
Into the pharyngeal arches and play an inductive role in thymus development.
Into the pharyngeal arches and form the parafollicular cell or ultimobranchial bodies of the thyroid gland.
Into the pharyngeal arches and play an inductive role in parathyroid gland development.
Facial ectomesenchyme of the pharyngeal arches forming skeletal muscle, bone, and cartilage in the face.
Odontoblasts (dentin-producing cells) of the teeth.
Around the optic vesicle and the developing eye and contributes to many eye elements such the choroid, sclera, iris, and ciliary body. It also contributes to the attaching skeletal muscles of the eye.
Into the otic placode and participates in the inner ear development.
Sensory ganglia of the fifth, seventh, ninth and tenth cranial nerves.
Schwann cellsEndocrine gland
Endocrine glands are glands of the endocrine system that secrete their products, hormones, directly into the blood rather than through a duct. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid gland, parathyroid gland, hypothalamus and adrenal glands. The hypothalamus and pituitary gland are neuroendocrine organs.Etelcalcetide
Etelcalcetide (formerly velcalcetide, trade name Parsabiv) is a calcimimetic drug for the treatment of secondary hyperparathyroidism in patients undergoing hemodialysis. It is administered intravenously at the end of each dialysis session. Etelcalcetide functions by binding to and activating the calcium-sensing receptor in the parathyroid gland. Parsabiv is currently owned by Amgen and Ono Pharmaceuticals in Japan.Hypomagnesemia with secondary hypocalcemia
Hypomagnesemia with secondary hypocalcemia (HSH) is an autosomal recessive genetic disorder affecting intestinal magnesium absorption. Decreased intestinal magnesium reabsorption and the resulting decrease in serum magnesium levels is believed to cause lowered parathyroid hormone (PTH) output by the parathyroid gland. This results in decreased PTH and decreased serum calcium levels (hypocalcemia). This manifests in convulsions and spasms in early infancy which, if left untreated, can lead to mental retardation or death. HSH is caused by mutations in the TRPM6 gene.Hypoparathyroidism
Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone. This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary muscle contraction), and several other symptoms. The condition can be inherited, but it is also encountered after thyroid or parathyroid gland surgery, and it can be caused by immune system-related damage as well as a number of rarer causes. The diagnosis is made with blood tests, and other investigations such as genetic testing depending on the results. The treatment of hypoparathyroidism is limited by the fact that there is no exact form of the hormone that can be administered as replacement. However teriparatide, brand name Forteo, a biosimilar peptide to parathyroid hormone, may be given by injection. Calcium replacement or vitamin D can ameliorate the symptoms but can increase the risk of kidney stones and chronic kidney disease.Multiple endocrine neoplasia type 1
Multiple endocrine neoplasia type 1 is part of a group of disorders, the multiple endocrine neoplasias, that affect the endocrine system through development of neoplastic lesions in pituitary, parathyroid gland and pancreas.Oxyphil cell (parathyroid)
In the parathyroid gland, the parathyroid oxyphil cell is larger and lighter staining than the parathyroid chief cell.These cells can be found in clusters in the center of the section and at the periphery. Oxyphil cells appear at the onset of puberty, but have no known function. With nuclear medicine scans, they selectively take up the Technetium-sestamibi complex radiotracer to allow delineation of glandular anatomy.
Oxyphil cells have been shown to express parathyroid-relevant genes found in the chief cells and have the potential to produce additional autocrine/paracrine factors, such as parathyroid hormone-related protein (PTHrP) and calcitriol. More work needs to be done to fully understand the functions of these cells and their secretions.Parathyroid adenoma
A parathyroid adenoma is a benign tumor of the parathyroid gland. It generally causes hyperparathyroidism; there are very few reports of parathyroid adenomas that were not associated with hyperparathyroidism.A human being usually has four parathyroid glands located on the back surface of the thyroid in the neck. In order to maintain calcium metabolism the parathyroids secrete parathyroid hormone (PTH) which stimulating bones to release calcium and kidneys to reabsorb it from the urine into the blood therefore increasing its serum level; calcitonin action is just an opposite. When a parathyroid adenoma causes hyperparathyroidism, more parathyroid hormone is secreted, causing the calcium concentration of the blood to rise, resulting in hypercalcemia.Parathyroid chief cell
Parathyroid chief cells (also called parathyroid principal cells or simply parathyroid cells) are one of the two cell types of the parathyroid glands, along with oxyphil cells. The chief cells are much more prevalent in the parathyroid gland than the oxyphil cells. It is perceived that oxyphil cells may be derived from chief cells at puberty, as they are not present at birth like chief cells.Chief cells appear as a dark purple in an H&E stain, with the oxyphil cells staining as a lighter pink.They are polygonal in shape with a round nucleus.Parathyroid disease
Many conditions are associated with disorders of the function of the parathyroid gland. Parathyroid diseases can be divided into those causing hyperparathyroidism, and those causing hypoparathyroidism.Parathyroid neoplasm
A parathyroid neoplasm is a tumor of the parathyroid gland.
Parathyroiditis is a condition involving inflammation of the parathyroid gland.
It can be associated with hyperparathyroidism, though most cases are asymptomatic.Sestamibi parathyroid scintigraphy
A sestamibi parathyroid scan is a procedure in nuclear medicine which is performed to localize parathyroid adenoma, which causes Hyperparathyroidism. Adequate localization of parathyroid adenoma allows the surgeon to use a minimally invasive surgical approach.Stella Malucchi
Stella Malucchi (Thai: สเตลล่า มาลูกี้) is an Italian-Colombian model and actress. Fluent in the Thai language, she has primarily worked in Thailand, and has acted in two films, Tears of the Black Tiger and Angulimala.
For her first film, Tears of the Black Tiger, she was spotted in a Thai music video by director Wisit Sasanatieng, who thought she would be perfect for the role of Rumpoey. Through make-up and costuming, Malucchi was transformed into a young, noble-born Thai woman in 1950s Thailand. She studied at Ruamrudee International School.
Stella fell ill one week after she gave birth to her son on Jan 2, and was admitted into hospital On Jan 24, 2010. After being directly admitted into ICU, she lost consciousness and lapsed into a coma. Tests revealed that she had hyperparathyroidism, a rare disease in which a defective parathyroid gland allows dangerously high calcium levels (hypercalcaemia). Being too weak for an operation to remove her parathyroid, she was placed on an artificial lung and heart machine. After five days and requiring dialysis several times a day, Stella showed signs of improvement. Unfortunately, complications soon developed. A restricted blood-flow to her right leg caused infection and an above-the-knee amputation was required. Soon after the removal of the leg, and with signs of infection having disappeared, Stella's parathyroid gland was then safely removed, ensuring her survival. Stella woke from the coma one month after she was admitted.Thyroid ima artery
The thyroid ima artery (thyroidea ima artery, arteria thyroidea ima, thyroid artery of Neubauer or the lowest thyroid artery) is an artery of the head and neck. It is an anatomical variant that, when present, supplies blood to the thyroid gland primarily, or the trachea, the parathyroid gland and the thymus gland (as thymica accessoria) in rare cases. It has also been reported to be a compensatory artery when one or both of the inferior thyroid arteries are absent and in a few cases the only source of blood to the thyroid gland. It varies in origin, size, blood supply, and termination, and occurs in only 3–10% of the population. Because of the variations and rarity, it may lead to surgical complications.
Anatomy of the endocrine system
|Islets of pancreas|