Editing Parathyroid hormone

{{Short description|Mammalian protein found in humans}}
{{Use dmy dates|date=December 2023}}
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{{Infobox gene}}

'''Parathyroid hormone '''('''PTH'''), also called '''parathormone''' or '''parathyrin''',  is a [[peptide hormone]] secreted by the [[parathyroid gland]]s that regulates [[serum calcium]] and [[phosphate]] through its actions on the [[bone]], [[kidney]]s, and [[small intestine]]. PTH increases serum calcium levels and is counteracted by [[calcitonin]]. Additionally, it promotes the synthesis of [[calcitriol]], the active form of [[vitamin D]].<ref>{{cite book | vauthors = Khan M, Jose A, Sharma S | chapter = Physiology, Parathyroid Hormone |date=2022-10-29 | title = StatPearls | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK499940/ |access-date=2025-04-08 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29763115 }}</ref>

PTH influences [[bone remodeling]], which is an ongoing process in which [[bone tissue]] is alternately [[bone resorption|resorbed]] and [[ossification|rebuilt]] over time.  PTH is secreted in response to low blood serum [[Calcium in biology|calcium]] (Ca<sup>2+</sup>) levels.  PTH indirectly stimulates [[osteoclast]] activity within the bone matrix ([[osteon]]), in an effort to release more ionic calcium (Ca<sup>2+</sup>) into the blood to elevate a low serum calcium level.  The [[bone]]s store calcium from which the body can release into the blood as needed as needed to keep [[calcium in biology#Measurement|the amount of calcium in the blood]] at appropriate [[concentration|levels]] despite the ever-present challenges of [[metabolism]], [[stress (biology)|stress]], and [[nutrition]]al variations. PTH is the trigger for the bones to release the stored calcium into the blood.

PTH is secreted primarily by the [[parathyroid chief cell|chief cells]] of the parathyroid glands. The gene for PTH is located on chromosome 11. It is a [[polypeptide]] containing 84 [[amino acids]], which is a [[prohormone]]. It has a molecular mass around 9500 [[Dalton (unit)|Da]].<ref name="pmid4509319">{{cite journal | vauthors = Brewer HB, Fairwell T, Ronan R, Sizemore GW, Arnaud CD | title = Human parathyroid hormone: amino-acid sequence of the amino-terminal residues 1-34 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 69 | issue = 12 | pages = 3585–8 | year = 1972 | pmid = 4509319 | pmc = 389826 | doi = 10.1073/pnas.69.12.3585| bibcode = 1972PNAS...69.3585B | doi-access = free }}</ref>

There are two types of PTH receptors. [[Parathyroid hormone 1 receptor]]s, activated by the 34 N-terminal amino acids of PTH, are present at high levels on the cells of bone and kidney. [[Parathyroid hormone 2 receptor]]s are present at high levels on the cells of central nervous system, pancreas, testes, and placenta.<ref>{{cite book| title= Essentials of Human Physiology| vauthors = Nosek TM | chapter=Section 5/5ch6/s5ch6_11 |chapter-url=http://humanphysiology.tuars.com/program/section5/5ch6/s5ch6_11.htm |archive-url=https://web.archive.org/web/20160324124828/http://humanphysiology.tuars.com/program/section5/5ch6/s5ch6_11.htm|archive-date=2016-03-24}}</ref> The half-life of PTH is about 4 minutes.<ref name="pmid12324490">{{cite journal | vauthors = Bieglmayer C, Prager G, Niederle B | title = Kinetic analyses of parathyroid hormone clearance as measured by three rapid immunoassays during parathyroidectomy | journal = Clinical Chemistry | volume = 48 | issue = 10 | pages = 1731–8 | date = Oct 2002 | pmid = 12324490 | doi =  10.1093/clinchem/48.10.1731| url = http://www.clinchem.org/cgi/content/abstract/48/10/1731 | access-date = 2009-02-23 | archive-url = https://web.archive.org/web/20110607115802/http://www.clinchem.org/cgi/content/abstract/48/10/1731 | archive-date = 2011-06-07 | url-status = dead | doi-access = free }}</ref>

Disorders that yield too little or too much PTH, such as [[hypoparathyroidism]], [[hyperparathyroidism]], and [[paraneoplastic syndrome]]s can cause [[bone disease]], [[hypocalcemia]], and [[hypercalcemia]].
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==Structure==
hPTH-(1-84) crystallizes as a slightly bent, long, helical dimer. The extended [[alpha helix|helical]] conformation of hPTH-(1-84) is the likely bioactive conformation.<ref name="pmid10837469">{{cite journal | vauthors = Jin L, Briggs SL, Chandrasekhar S, Chirgadze NY, Clawson DK, Schevitz RW, Smiley DL, Tashjian AH, Zhang F | title = Crystal structure of human parathyroid hormone 1-34 at 0.9-A resolution | journal = The Journal of Biological Chemistry | volume = 275 | issue = 35 | pages = 27238–44 | date = Sep 2000 | pmid = 10837469 | doi = 10.1074/jbc.M001134200 | doi-access = free }}</ref> The [[N-terminus|N-terminal]] fragment 1-34 of parathyroid hormone (PTH) has been crystallized and the structure has been refined to 0.9 [[Angstrom|Å]] resolution.
{|
|[[File:the ribbon cartoon structure.png|150px|thumb|left|Helical dimer structure of hPTH-(1-34)<ref name="pmid10881197">{{PDB|1ETE}}; {{cite journal | vauthors = Savvides SN, Boone T, Andrew Karplus P | title = Flt3 ligand structure and unexpected commonalities of helical bundles and cystine knots | journal = Nature Structural Biology | volume = 7 | issue = 6 | pages = 486–91 | date = Jun 2000 | pmid = 10881197 | doi = 10.1038/75896 }}</ref>]]
|}

== Function ==

=== Regulation of serum calcium ===
[[File:Parathyroid Hormone Negative Feedback.svg|thumb|left|The parathyroid gland releases PTH which keeps calcium in homeostasis.]]
{{Main|Calcium metabolism}}
[[File:Calcium balance 2.jpg|thumb|300px|right|A diagrammatic representation of the movements of calcium ions into and out of the blood plasma (the central square labeled  PLASMA Ca<sup>2+</sup>) in an adult in calcium balance:<br />The widths of the red arrows indicating movement into and out of the plasma are roughly in proportion to the daily amounts of calcium moved in the indicated directions.<br />The size of the central square in not in proportion to the size of the diagrammatic bone, which represents the calcium present in the skeleton, and contains about 25,000&nbsp;mmol (or 1&nbsp;kg) of calcium compared to the 9&nbsp;mmol (360&nbsp;mg) dissolved in the blood plasma.<br />The differently colored narrow arrows indicate where the specified hormones act, and their effects (“+” means stimulates; “-“ means inhibits) when their plasma levels are high.<br />PTH is parathyroid hormone, 1,25&nbsp;OH&nbsp;VIT D<sub>3</sub> is [[calcitriol]] or 1,25&nbsp;dihydroxyvitamin D<sub>3</sub>, and [[calcitonin]] is a hormone secreted by the [[thyroid gland]] when the plasma ionized calcium level is high or rising.<br />The diagram does not show the extremely small amounts of calcium that move into and out of the cells of the body, nor does it indicate the calcium that is bound to the extracellular proteins (in particular the plasma proteins) or to plasma phosphate.<ref name="pmid25287933" /><ref name="Brini">{{cite book | vauthors = Brini M, Ottolini D, Calì T, Carafoli E | veditors = Sigel A, Roland HK | title = Interrelations between Essential Metal Ions and Human Diseases | series = Metal Ions in Life Sciences | volume = 13 | year = 2013 | publisher = Springer | pages = 81–137 | chapter = Chapter 4. Calcium in Health and Disease | doi = 10.1007/978-94-007-7500-8_4 | pmid = 24470090 | isbn = 978-94-007-7499-5 }}</ref><ref name="Walter">{{cite book | vauthors= Walter F | title = Medical Physiology: A Cellular And Molecular Approach |publisher=Elsevier/Saunders |year=2003| chapter = The Parathyroid Glands and Vitamin D |page=1094 |isbn=1-4160-2328-3 }}</ref><ref name="guyton">Guyton A (1976). ‘’Medical Physiology’’. p.1062; New York, Saunders and Co.</ref><ref name="ganong">{{cite book | vauthors = Barrett KE, Barman SM, Boitano S, Brooks H | chapter = Chapter 23. Hormonal Control of Calcium & Phosphate Metabolism & the Physiology of Bone | veditors = Barrett KE, Barman SM, Boitano S, Brooks H | title = Ganong's Review of Medical Physiology | edition = 23e | chapter-url = http://www.accessmedicine.com/content.aspx?aID=5244785 | access-date = 2016-01-03 | archive-date = 2011-07-07 | archive-url = https://web.archive.org/web/20110707075939/http://www.accessmedicine.com/content.aspx?aID=5244785 | url-status = dead }}</ref>]]

Parathyroid hormone regulates [[serum calcium]] through its effects on bone, kidney, and the intestine:<ref name="pmid15180028">{{cite journal | vauthors = Coetzee M, Kruger MC | title = Osteoprotegerin-receptor activator of nuclear factor-kappaB ligand ratio: a new approach to osteoporosis treatment? | journal = Southern Medical Journal | volume = 97 | issue = 5 | pages = 506–11 | date = May 2004 | pmid = 15180028 | doi = 10.1097/00007611-200405000-00018 | s2cid = 45131847 }}</ref>

In bone, PTH enhances the release of calcium from the large reservoir contained in the bones.<ref>{{cite journal | vauthors = Poole KE, Reeve J | title = Parathyroid hormone - a bone anabolic and catabolic agent | journal = Current Opinion in Pharmacology | volume = 5 | issue = 6 | pages = 612–7 | date = Dec 2005 | pmid = 16181808 | doi = 10.1016/j.coph.2005.07.004 }}</ref> [[Bone resorption]] is the normal destruction of bone by [[osteoclast]]s, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to [[osteoblast]]s, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL and inhibits their secretion of [[osteoprotegerin]] (OPG). Free OPG competitively binds to [[RANKL]] as a [[decoy receptor]], preventing RANKL from interacting with [[RANK]], a receptor for RANKL. The binding of RANKL to RANK (facilitated by the decreased amount of OPG available for binding the excess RANKL) stimulates osteoclast precursors, which are of a [[monocyte]] lineage, to fuse. The resulting multinucleated cells are osteoclasts, which ultimately mediate [[bone resorption]]. Estrogen also regulates this pathway through its effects on PTH. Estrogen suppresses T cell TNF production by regulating T cell differentiation and activity in the bone marrow, thymus, and peripheral lymphoid organs. In the bone marrow, estrogen downregulates the proliferation of hematopoietic stem cells through an IL-7 dependent mechanism.<ref name="pmid12633785">{{cite journal | vauthors = Bord S, Ireland DC, Beavan SR, Compston JE | title = The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts | journal = Bone | volume = 32 | issue = 2 | pages = 136–41 | year = 2003 | pmid = 12633785 | doi = 10.1016/S8756-3282(02)00953-5 }}</ref>

In the kidney, around 250&nbsp;mmol of calcium ions are filtered into the [[glomerular filtrate]] per day. Most of this (245&nbsp;mmol/d) is reabsorbed from the tubular fluid, leaving about 5&nbsp;mmol/d to be excreted in the urine. This reabsorption occurs throughout the tubule (most, 60–70%, of it in the [[proximal tubule]]), except in the thin segment of the [[loop of Henle]].<ref name="pmid25287933">{{cite journal | vauthors = Blaine J, Chonchol M, Levi M | title = Renal control of calcium, phosphate, and magnesium homeostasis | journal = Clinical Journal of the American Society of Nephrology | volume = 10 | issue = 7 | pages = 1257–72 | year = 2015 | pmid = 25287933 | doi = 10.2215/CJN.09750913 | pmc = 4491294 }}</ref> Circulating parathyroid hormone only influences the reabsorption that occurs in the [[distal tubule]]s and the [[Collecting duct system|renal collecting ducts]]<ref name="pmid25287933" /> (but see Footnote{{#tag:ref |This reduction in the rate of calcium excretion via the urine is a minor effect of high parathyroid hormone levels in the blood. The main determinant of the amount of calcium excreted into the urine per day is the plasma ionized calcium concentration itself. The plasma parathyroid hormone (PTH) concentration only increases or decreases the amount of calcium excreted at any ''specified plasma ionized calcium concentration''. Thus, in primary [[hyperparathyroidism]], the quantity of calcium excreted in the urine per day is ''increased'' despite the high levels of PTH in the blood, because hyperparathyroidism results in [[hypercalcemia]], which increases the urinary calcium concentration ([[hypercalcuria]]) despite the moderately increased rate of calcium reabsorption from the renal tubular fluid caused by PTH's direct effect on those tubules. [[Renal stones]] are, therefore, often a first indication of hyperparathyroidism, especially since the hypercalcuria is accompanied by an increase in urinary phosphate excretion (a direct result of the high plasma PTH levels). Together the calcium and phosphate tend to precipitate out as water-insoluble salts, which readily  form solid "stones".<ref name="pmid25287933" /><ref name=Harrison>{{cite book | vauthors = Harrison TR, Adams RD, Bennett IL, Resnick WH, Thorn GW, Wintrobe MM | title = Principles of Internal Medicine | url = https://archive.org/details/in.ernet.dli.2015.549088 | edition = Third | date = 1958 | publisher = McGraw-Hill Book Company | location = New York | pages = 575–578 | chapter = Metabolic and Endocrine Disorders }}</ref><ref>{{cite web | url = http://www.parathyroid.com/parathyroid-symptoms.htm | title = Symptoms of Hyperparathyroidism and Symptoms of Parathyroid Disease. | work = Parathyroid.com | publisher = Norman Parathyroid Center | access-date = 2015-12-30 }}</ref> |group=nb}}). A more important effect of PTH on the kidney is, however, its inhibition of the reabsorption of [[phosphate]] (HPO<sub>4</sub><sup>2−</sup>) from the tubular fluid, resulting in a decrease in the plasma phosphate concentration.  Phosphate ions form water-insoluble salts with calcium. Thus, a decrease in the phosphate concentration of the  blood plasma (for a given total calcium concentration) increases the amount of calcium that is ionized.<ref name="pmid6623048">{{cite journal | vauthors = Haldimann B, Vogt K | title = [Hyperphosphatemia and tetany following phosphate enema] | language = fr | journal = Schweizerische Medizinische Wochenschrift | volume = 113 | issue = 35 | pages = 1231–3 | year = 1983 | pmid = 6623048 }}</ref><ref name="pmid8915965">{{cite journal | vauthors = Sutters M, Gaboury CL, Bennett WM | title = Severe hyperphosphatemia and hypocalcemia: a dilemma in patient management | journal = Journal of the American Society of Nephrology | volume = 7 | issue = 10 | pages = 2056–61 | year = 1996 | doi = 10.1681/ASN.V7102056 | pmid = 8915965 }}</ref> A third important effect of PTH on the kidney is its stimulation of the conversion of [[25-hydroxy vitamin D]] into [[1,25-dihydroxy vitamin D]] ([[calcitriol]]), which is released into the circulation. This latter form of vitamin D is the active hormone which stimulates calcium uptake from the intestine.<ref name=stryer>{{cite book | vauthors = Stryer L | title = Biochemistry | edition = Fourth | location = New York | publisher = W.H. Freeman and Company | date = 1995 | page = 707 | isbn = 978-0-7167-2009-6 }}</ref>

Via the kidney, PTH enhances the absorption of calcium in the [[intestine]] by increasing the production of activated [[vitamin D]]. Vitamin D activation occurs in the kidney. PTH up-regulates [[25-hydroxyvitamin D3 1-alpha-hydroxylase|25-hydroxyvitamin D<sub>3</sub> 1-alpha-hydroxylase]], the enzyme responsible for 1-alpha [[hydroxylation]] of [[25-hydroxy vitamin D]], converting vitamin D to its active form (1,25-dihydroxy vitamin D). This activated form of vitamin D increases the absorption of calcium (as Ca<sup>2+</sup> ions) by the intestine via [[calbindin]].

PTH was one of the first hormones to be shown to use the G-protein [[adenylyl cyclase]] second messenger system.

=== Regulation of serum phosphate ===

PTH reduces the reabsorption of [[phosphate]] from the [[proximal tubule]] of the kidney,<ref>{{cite book | vauthors = Gardner D, Dolores S | page = 232 | title = Greenspan's Basic & Clinical Endocrinology | year=2011 | publisher = McGraw Hill | isbn = 978-0-07-162243-1 | edition = 9th }}</ref> which means more phosphate is excreted through the urine.

However, PTH enhances the uptake of phosphate from the intestine and bones into the blood. In the bone, slightly more calcium than phosphate is released from the breakdown of bone. In the intestines, absorption of both calcium and phosphate is mediated by an increase in activated vitamin D. The absorption of phosphate is not as dependent on vitamin D as is that of calcium. The result of PTH release is a small net drop in the serum concentration of phosphate.

=== Vitamin D synthesis ===

PTH upregulates the activity of [[1-α-hydroxylase]] enzyme, which converts 25-hydroxycholecalciferol, the major circulating form of inactive vitamin D, into 1,25-dihydroxycholecalciferol, the active form of vitamin D, in the kidney.

==== Interactive pathway map ====

{{VitaminDSynthesis WP1531|highlight=Parathyroid_hormone}}

== Regulation of PTH secretion ==

Secretion of parathyroid hormone is determined chiefly by [[blood plasma|serum]] [[Blood calcium|ionized calcium]] concentration through [[feedback inhibition|negative feedback]]. Parathyroid cells express [[calcium-sensing receptor]]s on the cell surface. PTH is secreted when [Ca<sup>2+</sup>] is decreased (calcitonin is secreted when serum calcium levels are elevated). The G-protein-coupled calcium receptors bind extracellular calcium and may be found on the surface on a wide variety of cells distributed in the [[brain]], [[heart]], [[skin]], [[stomach]], C cells, and other tissues.  In the parathyroid gland, high concentrations of extracellular calcium result in activation of the Gq G-protein coupled cascade through the action of [[phospholipase C]].  This hydrolyzes [[phosphatidylinositol 4,5-bisphosphate]] (PIP2) to liberate intracellular messengers [[Inositol trisphosphate|IP3]] and [[diacylglycerol]] (DAG).  Ultimately, these two messengers result in a release of calcium from intracellular stores into the cytoplasmic space.  Hence a high extracellular calcium concentration leads to an increase in the cytoplasmic calcium concentration.  In contrast to the mechanism that most secretory cells use, this high cytoplasmic calcium concentration inhibits the fusion of vesicles containing granules of preformed PTH with the membrane of the parathyroid cell, and thus inhibits release of PTH.

In the parathyroids, magnesium serves this role in stimulus-secretion coupling. A mild decrease in serum magnesium levels stimulates the reabsorptive activity PTH has on the kidneys. Severe [[hypomagnesemia]] inhibits PTH secretion and also causes resistance to PTH, leading to a form of hypoparathyroidism that is reversible.<ref name="pmid10405219">{{cite journal | vauthors = Agus ZS | title = Hypomagnesemia | journal = Journal of the American Society of Nephrology | volume = 10 | issue = 7 | pages = 1616–22 | date = Jul 1999 | doi = 10.1681/ASN.V1071616 | pmid = 10405219 | doi-access = free }}</ref>

=== Stimulators ===

* Decreased serum [Ca<sup>2+</sup>].
* Mild decreases in serum [Mg<sup>2+</sup>].
* An increase in serum phosphate (increased phosphate causes it to complex with serum calcium,  forming calcium phosphate, which reduces stimulation of Ca-sensitive receptors (CaSr) that do not sense calcium phosphate, triggering an increase in PTH). 
* Adrenaline 
* Histamine

=== Inhibitors ===

* Increased serum [Ca<sup>2+</sup>].
* Severe decreases in serum [Mg<sup>2+</sup>], which also produces symptoms of [[hypoparathyroidism]] (such as [[hypocalcemia]]).<ref name=brs>{{cite book | vauthors = Costanzo LS | title = BRS Physiology | publisher = Lippincott, Williams, & Wilkins | year = 2007 | pages = [https://archive.org/details/physiology00cost_0/page/260 260] | url = https://archive.org/details/physiology00cost_0/page/260 | isbn = 978-0-7817-7311-9 | url-access = registration }}</ref>
* Calcitriol
*Increase in serum phosphate. Fibroblast growth factor-23 (FGF23) is produced in osteoblasts (from bone) in response to increases in serum phosphate (Pi). It binds to the fibroblast growth factor receptor of the parathyroid and suppresses PTH release. This may seem contradictory because PTH actually helps rid the blood of phosphates but it is also causes release of phosphate into the blood from bone resorption. FGF23 inhibits PTH and then takes its place helping inhibit re-absorption of phosphate in the kidney without the phosphate releasing effect on bones.<ref>{{cite journal | vauthors = Blaine J, Chonchol M, Levi M | title = Renal control of calcium, phosphate, and magnesium homeostasis | journal = Clinical Journal of the American Society of Nephrology | volume = 10 | issue = 7 | pages = 1257–72 | date = July 2015 | pmid = 25287933 | doi = 10.2215/CJN.09750913 | pmc = 4491294 }}</ref><ref>{{cite journal | vauthors = Carrillo-López N, Fernández-Martín JL, Cannata-Andía JB | title = [The role of calcium, calcitriol and their receptors in parathyroid regulation] | journal = Nefrologia | volume = 29 | issue = 2 | pages = 103–8 | date = 2009-04-01 | pmid = 19396314 | doi = 10.3265/Nefrologia.2009.29.2.5154.en.full | url = http://www.revistanefrologia.com/en-the-role-calcium-calcitriol-its-articulo-X2013251409004850 }}</ref>

== Disorders ==

[[Hyperparathyroidism]], the presence of excessive amounts of parathyroid hormone in the blood, occurs in two very distinct sets of circumstances. Primary hyperparathyroidism is due to autonomous, abnormal hypersecretion of PTH from the parathyroid gland, while [[secondary hyperparathyroidism]] is an appropriately high PTH level seen as a physiological response to [[hypocalcemia]]. A low level of PTH in the blood is known as  [[hypoparathyroidism]] and is most commonly due to damage to or removal of parathyroid glands during thyroid surgery.

There are a number of rare but well-described genetic conditions affecting parathyroid hormone metabolism, including [[pseudohypoparathyroidism]], [[familial hypocalciuric hypercalcemia]], and autosomal dominant hypercalciuric hypocalcemia. Of note, PTH is unchanged in [[pseudopseudohypoparathyroidism]]. In [[Osteoporosis|osteoporotic]] women, administration of an exogenous parathyroid hormone analogue ([[teriparatide]], by daily injection) superimposed on estrogen therapy produced increases in bone mass and reduced vertebral and nonvertebral fractures by 45–65%.<ref name="pmid11346808">{{cite journal | vauthors = Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH | title = Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis | journal = The New England Journal of Medicine | volume = 344 | issue = 19 | pages = 1434–41 | date = May 2001 | pmid = 11346808 | doi = 10.1056/NEJM200105103441904 | doi-access = free }}</ref>

== Measurement ==

PTH can be measured in the blood in several different forms: intact PTH; N-terminal PTH; mid-molecule PTH, and C-terminal PTH, and different tests are used in different clinical situations. The level may be stated in pg/dL or pmol/L (sometimes abbreviated mmol/L); multiply by 0.1060 to convert from pg/dL to pmol/L.<ref>{{cite web|url=https://unitslab.com/node/130|title=Parathyroid hormone (PTH) unit conversion (online calculator)|website=Unitslab}}</ref>

A US source states the average PTH level to be 8–51 pg/mL.<ref>{{cite book | vauthors =  Longo DL, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J | title = Harrison's Principles of Internal Medicine | date = 2012 | publisher = McGraw-Hill | location = New York | isbn = 978-0-07-174889-6 | page = 3594 | edition = 18th }}</ref> In the UK the [[Reference ranges for blood tests|biological reference range]] is considered to be 1.6–6.9 pmol/L.<ref>{{cite web|url=https://mft.nhs.uk/app/uploads/2020/09/Parathyroid-hormone-PTH.pdf|publisher=Manchester University NHS Foundation Trust (UK)|title=Division of Laboratory Medicine: Parathyroid hormone|access-date=23 April 2022|archive-date=2 February 2023|archive-url=https://web.archive.org/web/20230202080428/https://mft.nhs.uk/app/uploads/2020/09/Parathyroid-hormone-PTH.pdf|url-status=dead}}</ref> Normal total plasma calcium level ranges from 8.5 to 10.2&nbsp;mg/dL (2.12&nbsp;mmol/L to 2.55&nbsp;mmol/L).<ref>{{cite web | url = https://www.nlm.nih.gov/medlineplus/ency/article/003477.htm | title = MedlinePlus Medical Encyclopedia: Serum calcium | publisher = National Library of Medicine, National Institutes of Health |access-date=2009-02-01 | vauthors = Zieve D }}</ref>

===Interpretive guide===

The intact PTH and calcium normal ranges are different for age; calcium is also different for sex.<ref>[https://testdirectory.questdiagnostics.com/test/test-detail/8837/pth-intact-and-calcium?cc=MASTER PTH, Intact and Calcium] Test Detail. [[Quest Diagnostics]] Lab.  Accessed 2019-06-29.</ref><ref>[https://www.labcorp.com/test-menu/32766/parathyroid-hormone-pth-plus-calcium Parathyroid Hormone (PTH) Plus Calcium]. [[LabCorp]]. Accessed 2019-07-02.</ref>

{| class=wikitable
|-
!Condition || Intact PTH || Calcium
|- 
|Normal Parathyroid || Normal ||Normal 
|-
|[[Hypoparathyroidism]] ||Low or Low Normal <ref name=quest group=note>Low Normal or Normal only for Quest Lab, not LabCorp</ref>|| Low 
|-
|[[Hyperparathyroidism]]
|-    
| -  [[Primary hyperparathyroidism|Primary]] || High or Normal <ref name=quest group=note/>  ||High 
|-
|  - [[Secondary hyperparathyroidism|Secondary]] ||High ||Normal or Low 
|-
| -  [[Tertiary hyperparathyroidism|Tertiary]]<ref group=note>Both primary and tertiary hyperparathyroidism may have high PTH and high calcium. Tertiary is differentiated from primary hyperparathyroidism by a history of [[chronic kidney failure]] and secondary hyperparathyroidism.
</ref>||High ||High 
|-
|Non-Parathyroid [[Hypercalcemia]] ||Low or Low Normal <ref name=quest group=note/> || High
|}
{{reflist|group=note}}

== Medical uses ==
=== Recombinant human parathyroid hormone ===
{{Excerpt|Recombinant human parathyroid hormone}}

=== Teriparatide ===
{{Excerpt|Teriparatide|templates=-Drugbox}}

== See also ==
* [[Disorders of calcium metabolism]]
* [[Parathyroid hormone family]]
* [[Parathyroid hormone-related protein]]

==Footnote==
{{reflist|group=nb}}

== References ==
{{Reflist|refs=
<ref name="Teriparatide Forteo FDA label">{{cite web | title=Forteo- teriparatide injection, solution | website=DailyMed | date=29 April 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aae667c5-381f-4f92-93df-2ed6158d07b0 | access-date=8 March 2023 | archive-date=19 January 2022 | archive-url=https://web.archive.org/web/20220119181715/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aae667c5-381f-4f92-93df-2ed6158d07b0 | url-status=live }}</ref>
}}

== Further reading ==
{{refbegin|30em}}
* {{cite journal | vauthors = Drüeke TB, Massy ZA | title = Advanced oxidation protein products, parathyroid hormone and vascular calcification in uremia | journal = Blood Purification | volume = 20 | issue = 5 | pages = 494–7 | year = 2003 | pmid = 12207101 | doi = 10.1159/000065203 | s2cid = 46752152 }}
* {{cite journal | vauthors = Parfitt AM | title = Parathyroid hormone and periosteal bone expansion | journal = Journal of Bone and Mineral Research | volume = 17 | issue = 10 | pages = 1741–3 | date = Oct 2002 | pmid = 12369776 | doi = 10.1359/jbmr.2002.17.10.1741 | s2cid = 37111637 }}
* {{cite journal | vauthors = Martin TJ | title = Does bone reabsorption inhibition affect the anabolic response to parathyroid hormone? | journal = Trends in Endocrinology and Metabolism | volume = 15 | issue = 2 | pages = 49–50 | date = Mar 2004 | pmid = 15080150 | doi = 10.1016/j.tem.2004.01.002 | s2cid = 35482527 }}
* {{cite journal | vauthors = Keutmann HT, Sauer MM, Hendy GN, O'Riordan LH, Potts JT | title = Complete amino acid sequence of human parathyroid hormone | journal = Biochemistry | volume = 17 | issue = 26 | pages = 5723–9 | date = Dec 1978 | pmid = 728431 | doi = 10.1021/bi00619a019 }}
* {{cite journal | vauthors = Keutmann HT, Niall HD, O'Riordan JL, Potts JT | title = A reinvestigation of the amino-terminal sequence of human parathyroid hormone | journal = Biochemistry | volume = 14 | issue = 9 | pages = 1842–7 | date = May 1975 | pmid = 1125201 | doi = 10.1021/bi00680a006 }}
* {{cite journal | vauthors = Parkinson DB, Thakker RV | title = A donor splice site mutation in the parathyroid hormone gene is associated with autosomal recessive hypoparathyroidism | journal = Nature Genetics | volume = 1 | issue = 2 | pages = 149–52 | date = May 1992 | pmid = 1302009 | doi = 10.1038/ng0592-149 | s2cid = 24032313 }}
* {{cite journal | vauthors = Handt O, Reis A, Schmidtke J | title = Ectopic transcription of the parathyroid hormone gene in lymphocytes, lymphoblastoid cells and tumour tissue | journal = The Journal of Endocrinology | volume = 135 | issue = 2 | pages = 249–56 | date = Nov 1992 | pmid = 1474331 | doi = 10.1677/joe.0.1350249 }}
* {{cite journal | vauthors = Tonoki H, Narahara K, Matsumoto T, Niikawa N | title = Regional mapping of the parathyroid hormone gene (PTH) by cytogenetic and molecular studies | journal = Cytogenetics and Cell Genetics | volume = 56 | issue = 2 | pages = 103–4 | year = 1991 | pmid = 1672845 | doi = 10.1159/000133059 }}
* {{cite journal | vauthors = Marx UC, Adermann K, Bayer P, Meyer M, Forssmann WG, Rösch P | title = Structure-activity relation of NH2-terminal human parathyroid hormone fragments | journal = The Journal of Biological Chemistry | volume = 273 | issue = 8 | pages = 4308–16 | date = Feb 1998 | pmid = 9468478 | doi = 10.1074/jbc.273.8.4308 | s2cid = 1009667 | doi-access = free }}
* {{cite journal | vauthors = Arnold A, Horst SA, Gardella TJ, Baba H, Levine MA, Kronenberg HM | title = Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism | journal = The Journal of Clinical Investigation | volume = 86 | issue = 4 | pages = 1084–7 | date = Oct 1990 | pmid = 2212001 | pmc = 296835 | doi = 10.1172/JCI114811 }}
* {{cite journal | vauthors = Nussbaum SR, Gaz RD, Arnold A | title = Hypercalcemia and ectopic secretion of parathyroid hormone by an ovarian carcinoma with rearrangement of the gene for parathyroid hormone | journal = The New England Journal of Medicine | volume = 323 | issue = 19 | pages = 1324–8 | date = Nov 1990 | pmid = 2215618 | doi = 10.1056/NEJM199011083231907 | doi-access = free }}
* {{cite journal | vauthors = Ahn TG, Antonarakis SE, Kronenberg HM, Igarashi T, Levine MA | title = Familial isolated hypoparathyroidism: a molecular genetic analysis of 8 families with 23 affected persons | journal = Medicine | volume = 65 | issue = 2 | pages = 73–81 | date = Mar 1986 | pmid = 3005800 | doi = 10.1097/00005792-198603000-00001 | s2cid = 25332134 | doi-access = free }}
* {{cite journal | vauthors = Tregear GW, van Rietschoten J, Greene E, Niall HD, Keutmann HT, Parsons JA, O'Riordan JL, Potts JT | title = Solid-phase synthesis of the biologically active N-terminal 1 - 34 peptide of human parathyroid hormone | journal = Hoppe-Seyler's Zeitschrift für Physiologische Chemie | volume = 355 | issue = 4 | pages = 415–21 | date = Apr 1974 | pmid = 4474131 | doi = 10.1515/bchm2.1974.355.1.415 | s2cid = 43509130 }}
* {{cite journal | vauthors = Niall HD, Sauer RT, Jacobs JW, Keutmann HT, Segre GV, O'Riordan JL, Aurbach GD, Potts JT | title = The amino-acid sequence of the amino-terminal 37 residues of human parathyroid hormone | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 71 | issue = 2 | pages = 384–8 | date = Feb 1974 | pmid = 4521809 | pmc = 388010 | doi = 10.1073/pnas.71.2.384 | bibcode = 1974PNAS...71..384N | doi-access = free }}
* {{cite journal | vauthors = Andreatta RH, Hartmann A, Jöhl A, Kamber B, Maier R, Riniker B, Rittel W, Sieber P | title = [Synthesis of sequence 1-34 of human parathyroid hormone] | journal = Helvetica Chimica Acta | volume = 56 | issue = 1 | pages = 470–3 | year = 1973 | pmid = 4721748 | doi = 10.1002/hlca.19730560139 }}
* {{cite journal | vauthors = Jacobs JW, Kemper B, Niall HD, Habener JF, Potts JT | title = Structural analysis of human proparathyroid hormone by a new microsequencing approach | journal = Nature | volume = 249 | issue = 453 | pages = 155–7 | date = May 1974 | pmid = 4833516 | doi = 10.1038/249155a0 | bibcode = 1974Natur.249..155J | s2cid = 4226663 }}
* {{cite journal | vauthors = Vasicek TJ, McDevitt BE, Freeman MW, Fennick BJ, Hendy GN, Potts JT, Rich A, Kronenberg HM | title = Nucleotide sequence of the human parathyroid hormone gene | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 80 | issue = 8 | pages = 2127–31 | date = Apr 1983 | pmid = 6220408 | pmc = 393770 | doi = 10.1073/pnas.80.8.2127 | bibcode = 1983PNAS...80.2127V | doi-access = free }}
* {{cite journal | vauthors = Mayer H, Breyel E, Bostock C, Schmidtke J | title = Assignment of the human parathyroid hormone gene to chromosome 11 | journal = Human Genetics | volume = 64 | issue = 3 | pages = 283–5 | year = 1983 | pmid = 6885073 | doi = 10.1007/BF00279412 | s2cid = 35197648 }}
* {{cite journal | vauthors = Hendy GN, Kronenberg HM, Potts JT, Rich A | title = Nucleotide sequence of cloned cDNAs encoding human preproparathyroid hormone | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 78 | issue = 12 | pages = 7365–9 | date = Dec 1981 | pmid = 6950381 | pmc = 349267 | doi = 10.1073/pnas.78.12.7365 | bibcode = 1981PNAS...78.7365H | doi-access = free }}
* {{cite journal | vauthors = Hendy GN, Bennett HP, Gibbs BF, Lazure C, Day R, Seidah NG | title = Proparathyroid hormone is preferentially cleaved to parathyroid hormone by the prohormone convertase furin. A mass spectrometric study | journal = The Journal of Biological Chemistry | volume = 270 | issue = 16 | pages = 9517–25 | date = Apr 1995 | pmid = 7721880 | doi = 10.1074/jbc.270.16.9517 | s2cid = 10879253 | doi-access = free }}
{{refend}}

==External links==
*{{Commons category-inline}}
*[https://web.archive.org/web/20121113144425/http://www.acb.org.uk/docs/NHLM/Parathyroid%20hormone.pdf Parathyroid hormone: analyte monograph] - the Association for Clinical Biochemistry and Laboratory Medicine 
* {{PDBe-KB2|P01270|Parathyroid hormone}}

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[[Category:Parathyroid hormone receptor agonists]]
[[Category:Peptide hormones]]
[[Category:Hormones of the parathyroid glands]]
[[Category:Hormones of calcium metabolism]]