Diagram showing structures in thehuman neck. The four green shaded areas represent the most common position of the parathyroid glands, which are generally four in number and situated behind the lateral lobes of thethyroid gland (shaded orange).
Thyroid and parathyroids as viewed from the front of the neck
Parathyroid glands are smallendocrine glands in the neck of humans and othertetrapods. Humans usually have four parathyroid glands, located on the back of thethyroid gland in variable locations. The parathyroid gland produces and secretesparathyroid 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 theepithelial lining of the third and fourthpharyngeal 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.
The parathyroid glands are two pairs of glands usually positioned behind the left and right lobes of thethyroid. Each gland is a yellowish-brown flat ovoid that resembles alentil seed, usually about 6 mm long and 3 to 4 mm wide, and 1 to 2 mm anteroposteriorly.[1] 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.[2] These glands are not visible or able to be felt during examination of the neck.[3]
Each parathyroid vein drains into the superior, middle and inferior thyroid veins. The superior and middle thyroid veins drain into theinternal jugular vein, and the inferior thyroid vein drains into thebrachiocephalic vein.[4]
The parathyroid glands are variable in number: three or more small glands,[5] and can usually be located on the posterior surface of the thyroid gland.[5] Occasionally, some individuals may have six, eight, or even more parathyroid glands.[3] Rarely, the parathyroid glands may be within the thyroid gland itself, the chest, or even thethymus.[5]
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 thethyroid.[6] Two unique types of cells are present in the parathyroid gland:
Chief cells, which synthesize and releaseparathyroid 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.[7]
Oxyphil cells, which are lighter in appearance and increase in number with age,[7] have an unknown function.[8]
In theearly development of the humanembryo, a series of fivepharyngeal arches and fourpharyngeal 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 theendoderm of the third and fourth pouch andneural crestmesenchyme.[5] The position of the glands reverses during embryological development. The pair of glands which is ultimatelyinferior develops from the third pouch with thethymus, whereas the pair of glands which is ultimatelysuperior 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.[9] 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'scalcium andphosphate levels within a very narrow range, so that thenervous andmuscular systems can function properly. The parathyroid glands do this by secretingparathyroid hormone (PTH).[11]
Parathyroid hormone (also known as parathormone) is a smallprotein that takes part in the control of calcium and phosphatehomeostasis, as well as bone physiology. Parathyroid hormone has effects antagonistic to those ofcalcitonin.[12]
Calcium. PTH increases blood calcium levels by directly stimulating osteoblasts and thereby indirectly stimulatingosteoclasts (through RANK/RANKL mechanism) to break down bone and release calcium. PTH increases gastrointestinal calcium absorption by activatingvitamin D, and promotes calcium conservation (reabsorption) by thekidneys.[12]
Phosphate. 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.[12]
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 ofparathyroid hormone in the blood.[13]
3D medical animation image showing hyperparathyroidism (right)
Hyperparathyroidism is the state in which there is excess parathyroid hormone circulating in the blood. This may cause bone pain and tenderness, due to increasedbone resorption. With increased circulating calcium, there may be other symptoms associated withhypercalcemia, most commonly dehydration. Hyperparathyroidism is most commonly caused by a benign proliferation of chief cells in one parathyroid gland, and rarely inMEN syndrome. This is known asprimary hyperparathyroidism,[13] which is generally managed bysurgical removal of the abnormal parathyroid gland.[14]
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 assecondary hyperparathyroidism.
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 astertiary hyperparathyroidism.[15]
The state of decreased parathyroid activity is known as hypoparathyroidism. This is most commonly associated with damage to the glands or their blood supply duringthyroid surgery – it may be associated with rarer genetic syndromes such asDiGeorge syndrome, which is inherited as anautosomal dominant syndrome. Hypoparathyroidism will occur after surgical removal of the parathyroid glands.[16]
Occasionally, an individual's tissues are resistant to the effects of parathyroid hormone. This is known aspseudohypoparathyroidism. 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 conditionAlbright's hereditary osteodystrophy. Pseudo-pseudohypoparathyroidism, one of thelongest words in the English language, is used to describe an individual with Albright's hereditary osteodystrophy with normal parathyroid hormone and serum calcium levels.[16]
Hypoparathyroidism may present with symptoms associated withdecreased calcium, and is generally treated withVitamin D analogues.[16]
The parathyroid glands were first discovered in theIndian rhinoceros byRichard Owen in 1852.[17] 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 byIvar Viktor Sandström (1852–1889), a Swedish medical student, in 1880 atUppsala University.[18] Unaware of Owen's description, he described the glands in hismonograph "On a New Gland in Man and Fellow Animals" as the "glandulae parathyroidae", noting its existence in dogs, cats, rabbits, oxen, horses and humans.[19][20] For several years, Sandström's description received little attention.[21]
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 musculartetany.William G. MacCallum in 1908, investigating tumours of the parathyroid, proposed their role in calcium metabolism.[20] He noted that "Tetany occurs spontaneously in many forms and may be produced by the destruction of the parathyroid glands".[22]
The first successful removal of the parathyroid may have been carried out in 1928 by medical doctor Isaac Y Olch, whoseintern 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.[20]
Parathyroid glands are found in all adulttetrapods; 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.[23]
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 beenevolutionarily derived from these fish gills.[10][24]
^abIllustrated Anatomy of the Head and Neck, Fehrenbach and Herring, Elsevier, 2012, p. 159
^abDrake, Richard L.; Vogl, Wayne; Tibbitts, Adam W.M. Mitchell; illustrations by Richard; Richardson, Paul (2005).Gray's anatomy for students. Philadelphia: Elsevier/Churchill Livingstone. p. 918.ISBN978-0-8089-2306-0.
^abcdWilliams, S. Jacob; dissections by David J. Hinchcliffe; photography by Mick A. Turton; illustrated by Amanda (2007).Human anatomy: a clinically-orientated approach (New ed.). Edinburgh: Churchill Livingstone.ISBN978-0-443-10373-5.{{cite book}}: CS1 maint: multiple names: authors list (link)[page needed]
^Lappas D, Noussios G, Anagnostis P, Adamidou F, Chatzigeorgiou A, Skandalakis P (September 2012). "Location, number and morphology of parathyroid glands: results from a large anatomical series".Anat Sci Int.87 (3):160–4.doi:10.1007/s12565-012-0142-1.PMID22689148.S2CID207431255.
^Larsen, William J. (2001).Human embryology (3rd ed.). Philadelphia, Pa.: Churchill Livingstone. pp. 377–8.ISBN0-443-06583-7.
^abcZajac, Jeffrey D; Danks, Janine A (July 2008). "The development of the parathyroid gland: from fish to human".Current Opinion in Nephrology and Hypertension.17 (4):353–356.doi:10.1097/MNH.0b013e328304651c.PMID18660669.S2CID7971353.
^abcHall, Arthur C. Guyton, John E. (2005).Textbook of medical physiology (11th ed.). Philadelphia: W.B. Saunders. pp. 985–8.ISBN978-0-7216-0240-0.{{cite book}}: CS1 maint: multiple names: authors list (link)
^Cave, A.J.E. (1953)."Richard Owen and the discovery of the parathyroid glands"(PDF). In E. Ashworth Underwood (ed.).Science, Medicine and History. Essays on the Evolution of Scientific Thought and Medical Practice. Vol. 2. Oxford University Press. pp. 217–222. Retrieved2009-07-20.
^"On a New Gland in Man and Several Mammals (Glandulæ Parathyreoideæ)".Journal of the American Medical Association.111 (2): 197. 9 July 1938.doi:10.1001/jama.1938.02790280087037.
^abcdDuBose, Joseph; Ragsdale, Timothy; Morvant, Jason (January 2005). ""Bodies so tiny": The history of parathyroid surgery".Current Surgery.62 (1):91–95.doi:10.1016/j.cursur.2004.07.012.PMID15708157.
^Carney, JA (Sep 1996). "The glandulae parathyroideae of Ivar Sandström. Contributions from two continents".The American Journal of Surgical Pathology.20 (9):1123–44.doi:10.1097/00000478-199609000-00010.PMID8764749.
^Councilman, WT (1913). "Chapter 1".Disease and Its Causes. United States: New York Henry Holt and Company London Williams and Norgate The University Press, Cambridge, U.S.ASINB0065T4O6Q.OCLC654587300.
![Intermediate magnification micrograph. H&E stain. The white round structures are fat cells. Adipose tissue comprises 25–40% of normal parathyroid gland tissue.[7]](/mt/?noimg=&dark=on&url=http%3a%2f%2fen.wikipedia.org%2fwiki%2fFile%3aParathyroid_gland_intermed_mag.jpg)
