Editing Hyperparathyroidism

{{Short description|Increase in parathyroid hormone levels}}
{{cs1 config|name-list-style=vanc}}
{{Infobox medical condition
| name            = Hyperparathyroidism
| image           = 3D Medical Animation still shot Hyperparathyroidism.jpg
| caption         = 3D diagram of hyperparathyroidism
| field           = [[Endocrinology]]
| symptoms        = None, [[kidney stone]]s, weakness, depression, bone pains, confusion, increased urination<ref name="Fraser-2009"/><ref name="NIDDK-2012"/><ref name="Michels-2013"/>
| complications   = [[Osteoporosis]]<ref name="NIDDK-2012"/><ref name="Michels-2013"/>
| onset           = 50 to 60<ref name="NIDDK-2012"/>
| duration        =
| types           = Primary, secondary
| causes          = '''Primary''': [[parathyroid adenoma]], multiple benign tumors, [[parathyroid cancer]]<ref name="Fraser-2009"/><ref name="NIDDK-2012"/><br />'''Secondary''': [[vitamin D deficiency]], [[chronic kidney disease]], [[hypocalcemia|low blood calcium]]<ref name="Fraser-2009"/>
| risks           =
| diagnosis       = [[hypercalcemia|High blood calcium]] and high PTH levels<ref name="NIDDK-2012"/>
| differential    =
| prevention      =
| treatment       = Monitoring, surgery, [[intravenous normal saline]], [[cinacalcet]]<ref name="Fraser-2009"/><ref name="NIDDK-2012"/>
| medication      =
| prognosis       =
| frequency       = ~2 per 1,000<ref name="Michels-2013"/>
| deaths          =
}}

<!-- Definition and symptoms -->
'''Hyperparathyroidism''' is an increase in [[parathyroid hormone]] (PTH) levels in the [[blood]].<ref name="Fraser-2009"/><ref name="Allerheiligen-1998">{{cite journal | vauthors = Allerheiligen DA, Schoeber J, Houston RE, Mohl VK, Wildman KM | title = Hyperparathyroidism | journal = American Family Physician | volume = 57 | issue = 8 | pages = 1795–802, 1807–8 | date = April 1998 | pmid = 9575320 }}</ref> This occurs from a disorder either within the [[parathyroid gland]]s ([[primary hyperparathyroidism]]) or as response to external stimuli ([[secondary hyperparathyroidism]]).<ref name="Fraser-2009"/> Symptoms of hyperparathyroidism are caused by inappropriately [[elevated blood calcium]] excreted from the bones into the blood stream in response to increased production of parathyroid hormone.<ref name="Fraser-2009" /> In healthy people, when blood calcium levels are high, parathyroid hormone levels should be low.  With long-standing hyperparathyroidism, the most common symptom is [[kidney stone]]s.<ref name="Fraser-2009"/> Other symptoms may include bone pain, weakness, depression, confusion, and increased urination.<ref name="Fraser-2009"/><ref name="NIDDK-2012">{{cite web|title=Primary Hyperparathyroidism|url=https://www.niddk.nih.gov/health-information/health-topics/endocrine/primary-hyperparathyroidism/Pages/fact-sheet.aspx|website=NIDDK|access-date=27 September 2016|date=August 2012|url-status=live|archive-url=https://web.archive.org/web/20161004223909/https://www.niddk.nih.gov/health-information/health-topics/endocrine/primary-hyperparathyroidism/Pages/fact-sheet.aspx|archive-date=4 October 2016}}</ref> Both primary and secondary may result in [[osteoporosis]] (weakening of the bones).<ref name="NIDDK-2012"/><ref name="Michels-2013"/><!-- Cause and diagnosis -->

In 80% of cases, primary hyperparathyroidism is due to a single [[benign tumor]] known as a [[parathyroid adenoma]].<ref name="Fraser-2009" /><ref name="NIDDK-2012" /> Most of the remainder are due to several of these adenomas.<ref name="Fraser-2009" /><ref name="NIDDK-2012" /> Very rarely it may be due to [[parathyroid cancer]].<ref name="NIDDK-2012" /> Secondary hyperparathyroidism typically occurs due to [[vitamin D deficiency]], [[chronic kidney disease]], or other causes of [[hypocalcemia|low blood calcium]].<ref name="Fraser-2009">{{cite journal | vauthors = Fraser WD | title = Hyperparathyroidism | journal = Lancet | volume = 374 | issue = 9684 | pages = 145–58 | date = July 2009 | pmid = 19595349 | doi = 10.1016/S0140-6736(09)60507-9 }}</ref> The diagnosis of primary hyperparathyroidism is made by finding elevated calcium and PTH in the blood.<ref name="NIDDK-2012" />

<!-- Treatment -->
Primary hyperparathyroidism may only be cured by removing the adenoma or overactive parathyroid glands.<ref name="McDow-2018">{{cite journal | vauthors = McDow AD, Sippel RS | title = Should Symptoms Be Considered an Indication for Parathyroidectomy in Primary Hyperparathyroidism? | journal = Clinical Medicine Insights. Endocrinology and Diabetes | volume = 11 | pages = 1179551418785135 | date = 2018-01-01 | pmid = 30013413 | pmc = 6043916 | doi = 10.1177/1179551418785135 }}</ref><ref name="Fraser-2009"/><ref name="NIDDK-2012"/> In asymptomatic patients who present with mildly elevated blood calcium levels, with otherwise normal kidneys, and with normal [[bone density]], monitoring may be all that is required.<ref name="NIDDK-2012"/> The medication [[cinacalcet]] may also be used to decrease PTH levels in those unable to have surgery although it is not a cure.<ref name="NIDDK-2012"/> In patients with very high blood calcium levels, treatment may include large amounts of [[Saline (medicine)|intravenous normal saline]].<ref name="Fraser-2009"/> Low vitamin D should be corrected in those with secondary hyperparathyroidism but low Vitamin D pre-surgery is controversial for those with primary hyperparathyroidism.<ref>{{cite journal | vauthors = Randle RW, Balentine CJ, Wendt E, Schneider DF, Chen H, Sippel RS | title = Should vitamin D deficiency be corrected before parathyroidectomy? | journal = The Journal of Surgical Research | volume = 204 | issue = 1 | pages = 94–100 | date = July 2016 | pmid = 27451873 | doi = 10.1016/j.jss.2016.04.022 }}</ref> Low vitamin D levels should be corrected post-parathyroidectomy.<ref name="NIDDK-2012"/>
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==Signs and symptoms==
In primary hyperparathyroidism, about 75% of people are "asymptomatic".<ref name="Fraser-2009" /> While most primary patients are asymptomatic at the time of diagnosis, 'asymptomatic' is poorly defined and represents only those without "obvious clinical sequelae" such as kidney stones, bone disease, or hypercalcemic crisis.<ref name="McDow-2018" />  These "asymptomatic" patients may have other symptoms such as depression, anxiety, gastrointestinal distress, and neuromuscular problems that are not counted as symptoms.<ref name="McDow-2018" />  The problem is often picked up incidentally during [[Blood test|blood work]] for other reasons, and the test results show a higher amount of calcium in the blood than normal.<ref name="Michels-2013" /> Many people only have [[non-specific symptoms]].<ref>{{Cite journal |last=Taniegra |first=Edna D. |date=2004-01-15 |title=Hyperparathyroidism |url=https://www.aafp.org/pubs/afp/issues/2004/0115/p333.html |journal=American Family Physician |language=en-US |volume=69 |issue=2 |pages=333–339|pmid=14765772 }}</ref>

Common manifestations of hypercalcemia include [[constipation]], [[vomiting]], weakness, lethargy, fatigue, depression, bone pain, muscle soreness ([[myalgia]]s), joint pain, decreased appetite, feelings of [[nausea]], abdominal pain, [[pancreatitis]], [[polyuria]], [[polydipsia]], cognitive impairment, [[kidney stone]]s ({{#tag:ref |Although [[parathyroid hormone]] (PTH) promotes the reabsorption of calcium from the kidneys' tubular fluid, thus '' decreasing'' the rate of urinary calcium excretion, its effect is only noticeable at any given plasma ionized calcium concentration. The primary determinant of the amount of calcium excreted into the urine per day is the 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]]). [[Kidney stone]]s 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="Blaine-2015">{{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 | pmc = 4491294 | doi = 10.2215/CJN.09750913 }}</ref><ref name="Harrison-1958">{{cite book| vauthors = Harrison TR, Adams RD, Bennett Jr IL, Resnick WH, Thorn GW, Wintrobe MM |title = Principles of Internal Medicine.|edition= Third|date=1958|publisher=McGraw-Hill Book Company.|location=New York| pages=575–578| chapter=Metabolic and Endocrine Disorders. }}</ref> |group=nb}}), vertigo and [[osteopenia]] or [[osteoporosis]].<ref>[http://www.endocrine.niddk.nih.gov/pubs/hyper/hyper.htm#symptoms Hyperparathyroidism] {{webarchive|url=https://web.archive.org/web/20110524101254/http://www.endocrine.niddk.nih.gov/pubs/hyper/hyper.htm |date=2011-05-24 }}. National Endocrine and Metabolic Diseases Information Service. May 2006.</ref><ref>{{cite journal | vauthors = McKenna K, Rahman K, Parham K | title = Otoconia degeneration as a consequence of primary hyperparathyroidism | journal = Medical Hypotheses | volume = 144 | pages = 109982 | date = November 2020 | pmid = 32531542 | doi = 10.1016/j.mehy.2020.109982 }}</ref> A history of acquired [[racquet nail]]s (brachyonychia) may be indicative of bone resorption.<ref>{{cite journal | vauthors = Baran R, Turkmani MG, Mubki T | title = Acquired racquet nails: a useful sign of hyperparathyroidism | journal = Journal of the European Academy of Dermatology and Venereology | volume = 28 | issue = 2 | pages = 257–9 | date = February 2014 | pmid = 23682576 | doi = 10.1111/jdv.12187 | doi-access = free }}</ref> Radiographically, hyperparathyroidism has a pathognomic finding of rugger jersey spine.<ref>{{cite web |url=https://radiopaedia.org/articles/rugger-jersey-spine-hyperparathyroidism-1 |title = Rugger jersey spine (hyperparathyroidism) {{!}} Radiology Reference Article {{!}} Radiopaedia.org| date=2 May 2008 }}</ref>  Parathyroid adenomas are very rarely detectable on clinical examination. Surgical removal of a parathyroid tumor eliminates the symptoms in most patients.{{citation needed|date=October 2021}}

In secondary hyperparathyroidism due to lack of vitamin D absorption, the parathyroid gland is behaving normally; clinical problems are due to bone resorption and manifest as bone syndromes such as [[rickets]], [[osteomalacia]], and [[renal osteodystrophy]].<ref>{{Cite web|title=Secondary Hyperparathyroidism: What is Secondary Hyperparathyroidism? Secondary Hyperparathyroidism Symptoms, Treatment, Diagnosis - UCLA|url=https://www.uclahealth.org/endocrine-center/secondary-hyperparathyroidism|access-date=2021-01-18|website=www.uclahealth.org}}</ref>

==Causes==
Causes of primary hyperparathyroidism include parathyroid adenoma (80% of patients), multiglandular disease usually seen as hyperplasia of the 4 parathyroid glands (15-20% of patients), parathyroid carcinoma (less than 1% of patients).<ref name="Bilezikian-2018">{{cite journal |last1=Bilezikian |first1=John P |last2=Bandeira |first2=Leonardo |last3=Khan |first3=Aliya |last4=Cusano |first4=Natalie E |title=Hyperparathyroidism |journal=The Lancet |date=January 2018 |volume=391 |issue=10116 |pages=168–178 |doi=10.1016/S0140-6736(17)31430-7 |pmid=28923463 }}</ref> Primary hyperparathyroidism occurs sporadically and most patients do not have a [[family history]].<ref name="Bilezikian-2018" /> Radiation exposure increases the risk of primary hyperparathyroidism.<ref name="Fraser-2009" /> Additional risk factors include [[lithium]]<ref>{{Cite journal |last1=Szalat |first1=Auryan |last2=Mazeh |first2=Haggi |last3=Freund |first3=Herbert R |date=February 2009 |title=Lithium-associated hyperparathyroidism: report of four cases and review of the literature |journal=European Journal of Endocrinology |volume=160 |issue=2 |pages=317–323 |doi=10.1530/EJE-08-0620 |pmid=19001061 |doi-access=free }}</ref> and [[thiazide diuretics]]<ref>{{Cite journal |last1=Griebeler |first1=Marcio L. |last2=Kearns |first2=Ann E. |last3=Ryu |first3=Euijung |last4=Thapa |first4=Prabin |last5=Hathcock |first5=Matthew A. |last6=Melton |first6=L. Joseph |last7=Wermers |first7=Robert A. |date=March 2016 |title=Thiazide-Associated Hypercalcemia: Incidence and Association With Primary Hyperparathyroidism Over Two Decades |journal=The Journal of Clinical Endocrinology & Metabolism |volume=101 |issue=3 |pages=1166–1173 |doi=10.1210/jc.2015-3964 |pmid=26751196 |pmc=4803175 }}</ref> exposure. A number of genetic conditions including [[multiple endocrine neoplasia syndrome]]s, hyperparathyroidism-jaw tumor syndrome,<ref>{{Cite journal |last1=du Preez |first1=Hannah |last2=Adams |first2=Ashok |last3=Richards |first3=Polly |last4=Whitley |first4=Simon |date=December 2016 |title=Hyperparathyroidism jaw tumour syndrome: a pictoral review |journal=Insights into Imaging |volume=7 |issue=6 |pages=793–800 |doi=10.1007/s13244-016-0519-0 |pmid=27651062 |pmc=5110477 }}</ref> [[familial hypocalciuric hypercalcemia]],<ref>{{cite journal |last1=Varghese |first1=Jeena |last2=Rich |first2=Thereasa |last3=Jimenez |first3=Camilo |title=Benign Familial Hypocalciuric Hypercalcemia |journal=Endocrine Practice |date=March 2011 |volume=17 |pages=13–17 |doi=10.4158/EP10308.RA |pmid=21478088 }}</ref> neonatal severe hyperparathyroidism also increase the risk.<ref name="Fraser-2009" /> [[Parathyroid adenoma]]s have been linked with [[DDT]] although a causal link has not yet been established.<ref>{{cite journal |display-authors=6 |vauthors=Hu X, Saunders N, Safley S, Smith MR, Liang Y, Tran V, Sharma J, Jones DP, Weber CJ |date=January 2021 |title=Environmental chemicals and metabolic disruption in primary and secondary human parathyroid tumors |journal=Surgery |volume=169 |issue=1 |pages=102–108 |doi=10.1016/j.surg.2020.06.010 |pmc=7845795 |pmid=32771296}}</ref> The most common causes for secondary hyperparathyroidism include vitamin D deficiency, chronic kidney disease, inadequate calcium intake, [[malabsorption]].<ref>{{cite book |doi=10.1016/B978-0-323-53114-6.00007-9 |chapter=Thyroid and Parathyroid Glands |title=Gnepp's Diagnostic Surgical Pathology of the Head and Neck |date=2021 |pages=606–688 |isbn=978-0-323-53114-6 | vauthors = Chernock R, Williams MD }}</ref> Tertiary hyperparathyroidism most commonly occurs from prolonged secondary hyperparathyroidism.<ref>{{cite journal |last1=Kanin |first1=Maralee R. |last2=Leung |first2=Angela M. |title=Overview of Thyroid and Parathyroid Disease—The Endocrinology Perspective |journal=Otolaryngologic Clinics of North America |date=February 2024 |volume=57 |issue=1 |pages=11–24 |doi=10.1016/j.otc.2023.07.007 |pmid=37634985 }}</ref>

== Development ==
The parathyroid is composed of 4 glands with 2 located superiorly and 2 located inferiorly.<ref name="Rosen-2023">{{Citation |last1=Rosen |first1=Ryan D. |title=Embryology, Parathyroid |date=2023 |url=http://www.ncbi.nlm.nih.gov/books/NBK554580/ |work=StatPearls |access-date=2023-11-02 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32119467 |last2=Bordoni |first2=Bruno}}</ref> The parathyroid glands are located on the posterior [[thyroid]] and are derived from the [[endoderm]] of the 3rd and 4th [[Pharyngeal pouch (embryology)|pharyngeal pouches]].<ref name="Rosen-2023" /> Specifically, the [[inferior parathyroid glands]] are derived from the 3rd pharyngeal pouch and the [[superior parathyroid glands]] are derived from the 4th pharyngeal pouch dorsal wing.<ref name="Scharpf-2016">{{cite journal |last1=Scharpf |first1=Joseph |last2=Kyriazidis |first2=Natalia |last3=Kamani |first3=Dipti |last4=Randolph |first4=Gregory |title=Anatomy and embryology of the parathyroid gland |journal=Operative Techniques in Otolaryngology-Head and Neck Surgery |date=September 2016 |volume=27 |issue=3 |pages=117–121 |doi=10.1016/j.otot.2016.06.003 }}</ref> The [[ultimopharyngeal body]] is derived from the 4th pharyngeal pouch ventral wing and the [[parafollicular cell]]s ( C-cells) are derived when the ultimopharyngeal bodies fuse with the posterolateral thyroid.<ref name="Scharpf-2016" /> The parathyroid glands separates from the pharyngeal wall and attaches to the posterior thyroid during the 7th week of [[human embryonic development]].<ref name="Rosen-2023" />

==Mechanism==
Normal parathyroid glands measure the [[ionized calcium]] (Ca<sup>2+</sup>) concentration in the blood and secrete parathyroid hormone accordingly; if the ionized calcium rises above normal, the secretion of PTH is decreased, whereas when the Ca<sup>2+</sup> level falls, parathyroid hormone secretion is increased.<ref name="Blaine-2015"/>

=== Regulation of PTH ===
Rapid PTH regulation is controlled by the parathyroid [[G protein-coupled receptor|G-protein coupled]], [[Calcium-sensing receptor|calcium sensing receptors]] which responds to fluctuations in serum calcium levels.<ref>{{cite journal |last1=Brown |first1=Edward M. |last2=MacLeod |first2=R. John |title=Extracellular Calcium Sensing and Extracellular Calcium Signaling |journal=Physiological Reviews |date=2001 |volume=81 |issue=1 |pages=239–297 |doi=10.1152/physrev.2001.81.1.239 |pmid=11152759 }}</ref> Alternatively, prolonged changes in serum calcium influences mRNA-binding proteins altering the encoding of PTH mRNA.<ref name=":0">{{Cite journal |last1=Kumar |first1=Rajiv |last2=Thompson |first2=James R. |date=February 2011 |title=The Regulation of Parathyroid Hormone Secretion and Synthesis |journal=Journal of the American Society of Nephrology |language=en |volume=22 |issue=2 |pages=216–224 |doi=10.1681/ASN.2010020186 |pmid=21164021 |pmc=5546216 }}</ref> There are also calcium independent mechanisms which include repression of PTH transcription through [[1,25-dihydroxyvitamin D|1α,25-dihydroxyvitamin D]] binding with the [[vitamin D receptor]].<ref name=":0" /> Furthermore, 1α,25-dihydroxyvitamin D also has an impact on the expression of calcium-sensing receptors, indirectly affecting PTH secretion.<ref name=":0" />

'''Effects of PTH on the Bones'''

PTH stimulates the bones to release calcium through multiple mechanisms. 1) PTH stimulates [[osteoblast]]s which increase expression of [[RANKL]] which causes differentiation of the osteoblasts into [[osteocyte]]s.<ref name=":1">{{Cite journal |last1=Silva |first1=Barbara C |last2=Bilezikian |first2=John P |date=June 2015 |title=Parathyroid hormone: anabolic and catabolic actions on the skeleton |journal=Current Opinion in Pharmacology |language=en |volume=22 |pages=41–50 |doi=10.1016/j.coph.2015.03.005|pmid=25854704 |pmc=5407089 }}</ref> 2) PTH inhibits secretion of [[osteoprotegerin]]a to allow for [[osteoclast]] differentiation.<ref name=":1" /> 3) PTH will also directly activate osteoclasts to cause bone resorption through degradation of [[hydroxyapatite]] and organic material.<ref name=":1" /> This then causes bone to release calcium into the blood.
[[File:Michelle Karam Parathyroid (2).svg|thumb|Effects of PTH bone resorption]]
'''Effects of PTH on the Kidneys'''

Calcium reabsorption in the nephron occurs in [[proximal convoluted tubule]] and at the [[Ascending limb of loop of Henle|ascending Loop of Henle]].<ref name=":3">{{Cite journal |last1=Arnaud |first1=C D |last2=Tenenhouse |first2=A M |last3=Rasmussen |first3=H |date=March 1967 |title=Parathyroid Hormone |journal=Annual Review of Physiology |volume=29 |issue=1 |pages=349–372 |doi=10.1146/annurev.ph.29.030167.002025 |pmid=5335437 }}</ref> PTH acts on the [[distal convoluted tubule]] and [[Collecting duct system|collecting duct]] to increase calcium reabsorption in the [[nephron]].<ref name=":3"/> PTH also acts on the proximal convoluted tubule to decrease [[phosphate]] reabsorption to lower the serum phosphate.<ref name=":3"/> This decreases formation of insoluble calcium phosphate salts leading to an increase in serum ionized calcium.

'''Effects of PTH on the Small Intestines'''

PTH stimulates the production of [[1-alpha-hydroxylase]] in the proximal convoluted tubule.<ref name=":3"/> This enzyme activation hydroxylates inactive [[25-hydroxycholecalciferol]] to active vitamin D [[125-Dihydroxycholecalciferol|(1, 25 dihydroxycholecalciferol]]).<ref name=":3" /> Active vitamin D allows for calcium absorption through [[Transcellular transport|transcellular]] and [[Paracellular transport|paracellular]] pathways.<ref name=":3" />

Secondary hyperparathyroidism occurs if the calcium level is abnormally low. The normal glands respond by secreting parathyroid hormone at a persistently high rate. This typically occurs when the [[Calcitriol|1,25 dihydroxyvitamin D<sub>3</sub>]] levels in the blood are low and [[hypocalcemia]] is present. A lack of 1,25 dihydroxyvitamin D<sub>3</sub> can result from a deficient dietary intake of [[vitamin D]], or from a lack of exposure of the skin to sunlight, so the body cannot make its own vitamin D from cholesterol.<ref name="Stryer-1995">{{cite book | vauthors = Stryer L | title= Biochemistry. |edition= Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |page= 707|isbn= 0-7167-2009-4 }}</ref> The resulting [[hypovitaminosis D]] is usually due to a partial combination of both factors. Vitamin D<sub>3</sub> (or [[cholecalciferol]]) is converted to 25-hydroxyvitamin D (or [[calcidiol]]) by the liver, from where it is transported via the circulation to the kidneys, and it is converted into the active hormone, 1,25 dihydroxyvitamin D<sub>3</sub>.<ref name="Blaine-2015" /><ref name="Stryer-1995" /> Thus, a third cause of secondary hyperparathyroidism is [[chronic kidney disease]]. Here the ability to manufacture 1,25 dihydroxyvitamin D<sub>3</sub> is compromised, resulting in hypocalcemia.{{citation needed|date=August 2020}}

==Diagnosis==
[[File:CTHeadPharHiPara.png|thumb|Calcification in the brain due to hyperparathyroidism]]
[[File:Pepper & Salt.JPG|thumb|Pepper & Salt, classical X-Ray appearance of hyperparathyroidism]]
The gold standard of diagnosis is the PTH [[immunoassay]]. Once an elevated PTH has been confirmed, the goal of diagnosis is to determine the type of hyperparathyroidism (primary, secondary, or tertiary hyperparathyroidism) by obtaining a serum [[calcium]], phosphate, and PTH levels.

{| class="wikitable"
! Serum calcium !! Phosphate !! Vitamin D Level !! PTH !! Likely type
 |-
 | ↑ || ↓ || ↑ || ↑/↔ || Primary hyperparathyroidism<ref name="Le-2017">{{cite book | vauthors = Le T, Bhushan V, Sochat M, Kallianos K, Chavda Y, Zureick AH, Kalani M  | date=2017 |title=First aid for the USMLE step 1 2017 |location=New York |publisher=Mcgraw-Hill Education |isbn=978-1-259-83763-0 }}</ref>
 |-
 | ↓/↔ || ↑ || ↓ || ↑ || Secondary hyperparathyroidism<ref name="Le-2017" />
|-
|↑
|↑
|↓
|↑
|Tertiary hyperparathyroidism<ref name=":2">{{Cite web |title=Primary Hyperparathyroidism: A Case-based Review {{!}} Clinician Reviews |url=https://www.mdedge.com/clinicianreviews/article/136564/endocrinology/primary-hyperparathyroidism-case-based-review/page/0/3 |access-date=2023-11-09 |website=www.mdedge.com |language=en}}</ref>
|}

Primary hyperparathyroidism has high [[calcium]], [[vitamin D]], and [[Parathyroid hormone|PTH]] levels and a low [[phosphate]] level.<ref name="Le-2017" /><ref name=":2" /> Secondary hyperparathyroidism has low serum calcium and vitamin D levels, and high phosphate and PTH levels.<ref name="Le-2017" /><ref name=":2" /> Tertiary hyperparathyroidism has high serum calcium, phosphate, and PTH and low vitamin D levels.<ref name="Le-2017" /><ref name=":2" /> Tertiary hyperparathyroidism is differentiated from primary hyperparathyroidism by a history of [[chronic kidney failure]] and secondary hyperparathyroidism.{{citation needed|date=August 2020}}

Hyperparathyroidism can cause [[hyperchloremia]] and increase renal [[bicarbonate]] loss, which may result in a normal anion gap metabolic acidosis.<ref name="Gasparri-2015" /> ALP level can be elevated due to bone turnover. Additionally further tests can be completed to rule out other causes and complications of hyperparathyroidism including a [[Urinary calcium|24-hour urinary calcium]] for familial hypocalciuric hypercalcemia, [[DEXA scan]] to evaluate for [[osteoporosis]], [[osteopenia]], or [[fragility fractures]], and genetic testing.<ref>{{Cite journal |last1=Minisola |first1=Salvatore |last2=Arnold |first2=Andrew |last3=Belaya |first3=Zhanna |last4=Brandi |first4=Maria Luisa |last5=Clarke |first5=Bart L. |last6=Hannan |first6=Fadil M. |last7=Hofbauer |first7=Lorenz C. |last8=Insogna |first8=Karl L. |last9=Lacroix |first9=André |last10=Liberman |first10=Uri |last11=Palermo |first11=Andrea |last12=Pepe |first12=Jessica |last13=Rizzoli |first13=René |last14=Wermers |first14=Robert |last15=Thakker |first15=Rajesh V. |date=November 2022 |title=Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism |journal=Journal of Bone and Mineral Research |volume=37 |issue=11 |pages=2315–2329 |doi=10.1002/jbmr.4665 |pmid=36245271 |doi-access=free |pmc=10092691 }}</ref><ref>{{Cite journal |last1=Lee |first1=Janet Y. |last2=Shoback |first2=Dolores M. |date=October 2018 |title=Familial hypocalciuric hypercalcemia and related disorders |journal=Best Practice & Research Clinical Endocrinology & Metabolism |language=en |volume=32 |issue=5 |pages=609–619 |doi=10.1016/j.beem.2018.05.004|pmid=30449544 |pmc=6767927 }}</ref><ref>{{Cite journal |last1=Eastell |first1=Richard |last2=Brandi |first2=Maria Luisa |last3=Costa |first3=Aline G. |last4=D'Amour |first4=Pierre |last5=Shoback |first5=Dolores M. |last6=Thakker |first6=Rajesh V. |date=October 2014 |title=Diagnosis of Asymptomatic Primary Hyperparathyroidism: Proceedings of the Fourth International Workshop |journal=The Journal of Clinical Endocrinology & Metabolism |volume=99 |issue=10 |pages=3570–3579 |doi=10.1210/jc.2014-1414 |pmid=25162666 }}</ref><ref name=":4">{{Cite web |title=A condition that causes an imbalance of calcium in the body-Hyperparathyroidism - Diagnosis & treatment |url=https://www.mayoclinic.org/diseases-conditions/hyperparathyroidism/diagnosis-treatment/drc-20356199 |access-date=2023-11-09 |website=Mayo Clinic |language=en}}</ref> Additionally a [[CT scan]] without contrast or [[renal ultrasound]] can be done to assess for [[nephrolithiasis]] and/or [[nephrocalcinosis]] if there is concern for it.<ref name=":4" />

===Differential diagnosis===
Differential diagnoses of hypercalcemia include humoral hypercalcemia of malignancy, renal failure, malignant bone destruction (such as [[multiple myeloma]], metastatic [[breast cancer]], [[lymphoma]]), thiazide diuretics, lithium, immobilization, [[hyperthyroidism]], [[Milk-alkali syndrome|milk alkali syndrome]], multiple endocrine adenomatosis syndromes, and [[granulomatous disease]]s.<ref>{{Cite journal |last1=Allerheiligen |first1=David A. |last2=Schoeber |first2=Joe |last3=Houston |first3=Robert E. |last4=Mohl |first4=Virginia K. |last5=Wildman |first5=Karen M. |date=1998-04-15 |title=Hyperparathyroidism |url=https://www.aafp.org/pubs/afp/issues/1998/0415/p1795.html |journal=American Family Physician |language=en-US |volume=57 |issue=8 |pages=1795–1802|pmid=9575320 }}</ref> Additionally, [[Familial benign hypocalciuric hypercalcaemia|familial benign hypocalciuric hypercalcamia]] can present with similar lab changes.<ref name="Fraser-2009"/> In this condition, the calcium creatinine clearance ratio, however, is typically under 0.01 due to the low levels urine calcium.<ref name="Fraser-2009"/>

===Blood tests===
====Intact PTH====
In primary hyperparathyroidism, parathyroid hormone (PTH) levels are either elevated or "inappropriately normal" in the presence of elevated calcium.  Typically, PTH levels vary greatly over time in the affected patient and (as with Ca and Ca++ levels) must be retested several times to see the pattern. The currently accepted test for PTH is ''intact PTH'', which detects only relatively intact and biologically active PTH molecules. Older tests often detected other, inactive fragments. Even intact PTH may be inaccurate in patients with kidney dysfunction.{{citation needed|date=August 2020}} Intact PTH blood tests may be falsely low if biotin has been ingested in the previous few days prior to the blood test.<ref>{{cite journal | vauthors = Waghray A, Milas M, Nyalakonda K, Siperstein AE | title = Falsely low parathyroid hormone secondary to biotin interference: a case series | journal = Endocrine Practice | volume = 19 | issue = 3 | pages = 451–5 | date = 2013 | pmid = 23337137 | doi = 10.4158/EP12158.OR }}</ref>

====Calcium levels====
In cases of primary hyperparathyroidism or tertiary hyperparathyroidism, heightened PTH leads to increased serum calcium (hypercalcemia) due to:{{citation needed|date=October 2021}}
# increased bone resorption, allowing the flow of calcium from bone to blood
# reduced kidney clearance of calcium
# increased intestinal calcium absorption

====Serum phosphate====
In primary hyperparathyroidism, serum phosphate levels are abnormally low as a result of decreased reabsorption of phosphate in the kidney tubules. However, this is only present in about 50% of cases. This contrasts with [[secondary hyperparathyroidism]] and tertiary hyperparathyroidism, in which serum phosphate levels are generally elevated because of kidney disease.{{citation needed|date=August 2020}}

====Alkaline phosphatase====
[[Alkaline phosphatase]] levels are usually high in hyperparathyroidism due to high bone turn over. In primary hyperparathyroidism, levels may remain within the normal range, but this is inappropriately normal given the increased levels of plasma calcium.{{citation needed|date=August 2020}}

===Nuclear medicine===
[[Nuclear medicine]] imaging methods are used by surgeons to locate which parathyroid gland is responsible for hyperparathyroidism or to find [[ectopia (medicine)|ectopic]] parathyroid adenomas, most commonly found in the anterior [[mediastinum]].{{Citation needed|date=August 2010}} Historically, [[Sestamibi parathyroid scan|technetium sestamibi scintigraphy]] was the main method used or this indication.<ref name="Neish">{{cite web |title=Parathyroid Adenoma |url=http://brighamrad.harvard.edu/Cases/bwh/hcache/17/full.html |url-status=dead |archive-url=https://web.archive.org/web/20110716192203/http://brighamrad.harvard.edu/Cases/bwh/hcache/17/full.html |archive-date=2011-07-16 |work=BrighamRAD Teaching Case Database |vauthors=Neish AS, Nagel JS, Holman BL}}</ref> Recently 18F-fluorocholine [[PET-CT|PET/CT]] tend to be more and more performed due to excellent diagnostic performance.<ref>{{Cite journal |last1=Giovanella |first1=Luca |last2=Bacigalupo |first2=Lorenzo |last3=Treglia |first3=Giorgio |last4=Piccardo |first4=Arnoldo |date=February 2021 |title=Will 18F-fluorocholine PET/CT replace other methods of preoperative parathyroid imaging? |journal=Endocrine |volume=71 |issue=2 |pages=285–297 |doi=10.1007/s12020-020-02487-y |pmid=32892309 }}</ref><ref>{{Cite journal |last1=Schweighofer-Zwink |first1=Gregor |last2=Hehenwarter |first2=Lukas |last3=Rendl |first3=Gundula |last4=Rettenbacher |first4=Lukas |last5=Langsteger |first5=Werner |last6=Beheshti |first6=Mohsen |last7=Pirich |first7=Christian |date=February 2019 |title=Darstellung und Lokalisation von Nebenschilddrüsenadenomen mit F‑18 Cholin PET/CT |journal=Wiener Medizinische Wochenschrift |language=de |volume=169 |issue=1–2 |pages=15–24 |doi=10.1007/s10354-018-0660-0 |doi-access=free |pmid=30264384 }}</ref>

===Classification===

====Primary====
[[File:Blausen 0533 Parathyroid adenoma.png|thumb|[[Parathyroid adenoma]].]]
[[Primary hyperparathyroidism]] results from a [[endocrine disease|hyperfunction]] of the [[parathyroid glands]] themselves. The oversecretion of PTH is due to a [[parathyroid adenoma]], [[parathyroid hyperplasia]], or rarely, a [[parathyroid carcinoma]]. This disease is often characterized by the quartet ''stones, bones, groans, and psychiatric overtones'' referring to the presence of [[kidney stone]]s, hypercalcemia, constipation, and [[peptic ulcer]]s, as well as [[major depressive disorder|depression]], respectively.<ref>{{cite journal | vauthors = Carroll MF, Schade DS | title = A practical approach to hypercalcemia | journal = American Family Physician | volume = 67 | issue = 9 | pages = 1959–66 | date = May 2003 | pmid = 12751658 | url = http://www.aafp.org/afp/2003/0501/p1959.html | url-status = live | quote = his constellation of symptoms has led to the mnemonic “Stones, bones, abdominal moans, and psychic groans,” which is used to recall the signs and symptoms of hypercalcemia, particularly as a result of primary hyperparathyroidism. | archive-url = https://web.archive.org/web/20140821185906/http://www.aafp.org/afp/2003/0501/p1959.html | archive-date = 21 August 2014 }}</ref><ref name="McConnell-2007">{{cite book| vauthors = McConnell TH |title=The Nature of Disease: Pathology for the Health Professions|url=https://archive.org/details/naturediseasepat00mcco|url-access=limited|year=2007|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-5317-3|page=[https://archive.org/details/naturediseasepat00mcco/page/n495 466]|quote="Stones" refers to kidney stones, "bones" to associated destructive bone changes, "groans" to the pain of stomach and peptic ulcers that occur in some cases, and "moans" to the depression that frequently accompanies the disease and is often its first and most prominent manifestation.}}</ref>

In a minority of cases, this occurs as part of a [[multiple endocrine neoplasia]] (MEN) syndrome, either [[multiple endocrine neoplasia type 1|type 1]] (caused by a mutation in the gene ''[[MEN1]]'') or [[multiple endocrine neoplasia type 2a|type 2a]] (caused by a mutation in the gene [[RET proto-oncogene|''RET'']]), which is also associated with the adrenal tumor [[pheochromocytoma]]. Other mutations that have been linked to parathyroid neoplasia include mutations in the genes ''[[HRPT2]]''  and [[Calcium-sensing receptor|''CASR'']].<ref name="Marx-2011">{{cite journal | vauthors = Marx SJ | title = Hyperparathyroid genes: sequences reveal answers and questions | journal = Endocrine Practice | volume = 17 | issue = Suppl 3| pages = 18–27 | date = 2011 | pmid = 21454225 | pmc = 3484688 | doi = 10.4158/EP11067.RA }}</ref><ref name="Sulaiman-2012">{{cite journal | vauthors = Sulaiman L, Nilsson IL, Juhlin CC, Haglund F, Höög A, Larsson C, Hashemi J | title = Genetic characterization of large parathyroid adenomas | journal = Endocrine-Related Cancer | volume = 19 | issue = 3 | pages = 389–407 | date = June 2012 | pmid = 22454399 | pmc = 3359501 | doi = 10.1530/ERC-11-0140 }}</ref>

Patients with [[bipolar disorder]] who are receiving long-term [[lithium (medication)|lithium]] treatment are at increased risk for hyperparathyroidism.<ref name="Pomerantz-2010">{{cite journal | vauthors = Pomerantz JM | year = 2010 | title = Hyperparathyroidism Resulting From Lithium Treatment Remains Underrecognized | url = http://dbt.consultantlive.com/display/article/1145628/1544855 | journal = Drug Benefit Trends | volume = 22 | pages = 62–63 | url-status=live | archive-url = https://web.archive.org/web/20100701080610/http://dbt.consultantlive.com/display/article/1145628/1544855 | archive-date = 2010-07-01 }}</ref> Elevated calcium levels are found in 15% to 20% of patients who have been taking lithium long-term. However, only a few of these patients have significantly elevated levels of parathyroid hormone and clinical symptoms of hyperparathyroidism. Lithium-associated hyperparathyroidism is usually caused by a single parathyroid adenoma.<ref name="Pomerantz-2010" />

====Secondary====
[[Secondary hyperparathyroidism]] is due to physiological (i.e. appropriate) secretion of [[parathyroid hormone]] (PTH) by the [[parathyroid gland]]s in response to [[hypocalcemia]] (low [[blood]] [[calcium]] levels). The most common causes are [[vitamin D deficiency]]<ref name="Lips-2001">{{cite journal | vauthors = Lips P | title = Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications | journal = Endocrine Reviews | volume = 22 | issue = 4 | pages = 477–501 | date = August 2001 | pmid = 11493580 | doi = 10.1210/edrv.22.4.0437 | doi-access = free }}</ref> (caused by lack of sunlight, diet or malabsorption) and [[chronic kidney failure]].{{citation needed|date=October 2021}}  Vitamin D deficiency can result from malabsorption or decreased vitamin D intake such as with [[Gastric bypass surgery|gastric bypass]], small bowel disease, [[pancreatic disease]], and [[Diet (nutrition)|dietary]] causes.<ref>{{Cite journal |last1=Compher |first1=Charlene W. |last2=Badellino |first2=Karen O. |last3=Boullata |first3=Joseph I. |date=February 2008 |title=Vitamin D and the Bariatric Surgical Patient: A Review |journal=Obesity Surgery |volume=18 |issue=2 |pages=220–224 |doi=10.1007/s11695-007-9289-6 |pmid=18176832 }}</ref> Other causes include decreased skin synthesis of vitamin D such as decreased exposure to sunlight and skin disorders. Insufficient vitamin D synthesis such as defective 25-hydroxylation, [[1-alpha-hydroxylase|1-alpha hydroxylase]], and 1-alpha 25-hydroxylation can also contribute to vitamin D deficiency.

Lack of vitamin D leads to reduced calcium absorption by the intestine leading to hypocalcemia and increased parathyroid hormone secretion. This increases bone resorption. In chronic kidney failure the problem is more specifically failure to convert vitamin D to its active form in the kidney. The bone disease in secondary hyperparathyroidism caused by kidney failure is termed [[renal osteodystrophy]].<ref>{{cite journal | others = Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group | title = KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) | journal = Kidney International Supplements | issue = 113 | pages = S1–130 | date = August 2009 | pmid = 19644521 | doi = 10.1038/ki.2009.188 | volume = 76 | last1 = Eckardt | first1 = Kai-Uwe | last2 = Kasiske | first2 = Bertram L. | doi-access = free }}</ref>

====Tertiary====
[[Tertiary hyperparathyroidism]] is seen in those with long-term secondary hyperparathyroidism, which eventually leads to hyperplasia of the parathyroid glands and a loss of response to serum calcium levels. This disorder is most often seen in patients with end-stage kidney disease and is an autonomous activity.<ref name="The Lecturio Medical Concept Library">{{cite web |url=https://www.lecturio.com/concepts/hyperparathyroidism/| title=Hyperparathyroidism|website=The Lecturio Medical Concept Library |access-date= 25 July 2021}}</ref> Patients with late-stage kidney disease have an increased likelihood of developing tertiary hyperparathyroidism if not promptly corrected.<ref name="van der Plas 271–278"/> In patients with late-stage kidney disease phosphate levels are elevated which directly affects the parathyroid glands and increases PTH production. Additionally, studies have shown that even in the absence of secondary hyperparathyroidism, those with X-Linked hypophosphatemia rickets who are on phosphate treatment are more susceptible to developing tertiary hyperparathyroidism.<ref>{{Cite journal |last1=Mäkitie |first1=Outi |last2=Kooh |first2=Sang Whay |last3=Sochett |first3=Etienne |date=February 2003 |title=Prolonged high-dose phosphate treatment: a risk factor for tertiary hyperparathyroidism in X-linked hypophosphatemic rickets |journal=Clinical Endocrinology |volume=58 |issue=2 |pages=163–168 |doi=10.1046/j.1365-2265.2003.01685.x |pmid=12580931 }}</ref>

==Treatment==
Treatment depends on the type of hyperparathyroidism encountered.

===Primary===
[[Parathyroidectomy]] is a curative therapy for symptomatic hyperparathyroidism. Additionally, it decrease the risk of [[Kidney stone disease|nephrolithiasis]], [[osteoporosis]], [[Pathologic fracture|fragility fractures]], and improves [[Bone density|bone mineral density]]. Studies have also found that parathyroidectomy for hyperparathyroidism improves [[fatigue]], [[weakness]], [[Depression (mood)|depression]], and memory. While parathyroidectomy is recommended for all patients with hyperparathyroidism who are symptomatic, indications of [[surgery]] for those who are asymptomatic include the following:<ref name="Bilezikian-2004">{{cite journal | vauthors = Bilezikian JP, Silverberg SJ | title = Clinical practice. Asymptomatic primary hyperparathyroidism | journal = The New England Journal of Medicine | volume = 350 | issue = 17 | pages = 1746–51 | date = April 2004 | pmid = 15103001 | doi = 10.1056/NEJMcp032200 | pmc = 3987990 }}</ref>
* Asymptomatic hyperparathyroidism with any of the following:
** 24-hour urinary calcium >250&nbsp;mg/day in women and >300&nbsp;mg/day in men (see [[#Notes|footnote]], below)
** serum calcium > 1&nbsp;mg/dl above upper limit of normal
** [[Creatinine clearance]] > 30% below normal for patient's age
** Estimated glomerular filtration rate <60 mL/min/1.73 m2
** Bone density > 2.5 standard deviations below peak (i.e., [[Bone density#T-score|T-score]] of −2.5)
** People age < 50
** Nephrolithiasis seen on imaging (ultrasound or CT)

A 2020 [[Cochrane (organisation)|Cochrane]] [[systematic review]] compared the surgical procedures of minimally invasive [[parathyroidectomy]] and classically used bilateral neck exploration, however it did not find one approach to be superior to the other in either benefits or risks.<ref>{{Cite journal |last1=Ahmadieh |first1=Hala |last2=Kreidieh |first2=Omar |last3=Akl |first3=Elie A |last4=El-Hajj Fuleihan |first4=Ghada |date=2020-10-21 |editor-last=Cochrane Metabolic and Endocrine Disorders Group |title=Minimally invasive parathyroidectomy guided by intraoperative parathyroid hormone monitoring (IOPTH) and preoperative imaging versus bilateral neck exploration for primary hyperparathyroidism in adults |journal=Cochrane Database of Systematic Reviews |volume=10 |issue=10 |pages=CD010787 |language=en |doi=10.1002/14651858.CD010787.pub2|pmid=33085088 |pmc=8094219 }}</ref>

Surgery can rarely result in [[hypoparathyroidism]].{{citation needed|date=October 2021}}

===Secondary===
In patients with secondary hyperparathyroidism, the high PTH levels are an appropriate response to low calcium and treatment must be directed at the underlying cause of this (usually [[vitamin D deficiency]] or [[Chronic kidney disease|chronic kidney failure]]). If this is successful, PTH levels return to normal levels, unless PTH secretion has become [[Autonomy|autonomous]] (tertiary hyperparathyroidism).<ref name="The Lecturio Medical Concept Library"/>  [[Hyperphosphatemia]] may be treated by decreasing dietary intake of phosphate. If phosphate remains persistently elevated above 5.5&nbsp;mg/dL with dietary restriction, then [[phosphate binder]]s may be used.<ref>{{Cite journal |last1=Ketteler |first1=Markus |last2=Block |first2=Geoffrey A. |last3=Evenepoel |first3=Pieter |last4=Fukagawa |first4=Masafumi |last5=Herzog |first5=Charles A. |last6=McCann |first6=Linda |last7=Moe |first7=Sharon M. |last8=Shroff |first8=Rukshana |last9=Tonelli |first9=Marcello A. |last10=Toussaint |first10=Nigel D. |last11=Vervloet |first11=Marc G. |last12=Leonard |first12=Mary B. |date=July 2017 |title=Executive summary of the 2017 KDIGO Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) Guideline Update: what's changed and why it matters |journal=Kidney International |language=en |volume=92 |issue=1 |pages=26–36 |doi=10.1016/j.kint.2017.04.006|pmid=28646995 |doi-access=free |hdl=1805/15063 |hdl-access=free }}</ref> Vitamin D deficiency may be treated with vitamin D supplementation. However in patients with chronic kidney disease, patients should not receive vitamin D supplementation if they are elevated serum phosphate levels or have hypercalcemia.<ref>{{Cite journal |last=Andrassy |first=Konrad M. |date=September 2013 |title=Comments on 'KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease' |journal=Kidney International |volume=84 |issue=3 |pages=622–623 |doi=10.1038/ki.2013.243 |pmid=23989362 |doi-access=free }}</ref>

=== Tertiary ===
[[Parathyroidectomy]] is indicated in tertiary hyperparathyroidism for patients who have severe [[osteopenia]], severe persistent [[Hypercalcaemia|hypercalcemia]] (>11.0&nbsp;mg/ dL), [[calciphylaxis]], bone pain, or pathological fracture.<ref>{{cite journal |last1=Palumbo |first1=V. |last2=Damiano |first2=G. |last3=Messina |first3=M. |title=Tertiary hyperparathyroidism: a review |journal=La Clinica Terapeutica |date=30 April 2021 |volume=172 |issue=3 |pages=241–246 |doi=10.7417/CT.2021.2322 |pmid=33956045 }}</ref> A systematic review found surgical treatment to be superior regarding cure rates than medical therapy with [[cinacalcet]] with lower risk of complications.<ref>{{cite journal |last1=Dulfer |first1=R R |last2=Franssen |first2=G J H |last3=Hesselink |first3=D A |last4=Hoorn |first4=E J |last5=van Eijck |first5=C H J |last6=van Ginhoven |first6=T M |title=Systematic review of surgical and medical treatment for tertiary hyperparathyroidism |journal=British Journal of Surgery |date=18 May 2017 |volume=104 |issue=7 |pages=804–813 |doi=10.1002/bjs.10554 |pmid=28518414 }}</ref>

===Calcimimetics===
A [[calcimimetic]] (such as [[cinacalcet]]) is a potential therapy for some people with severe hypercalcemia and primary hyperparathyroidism who are unable to undergo parathyroidectomy, and for secondary hyperparathyroidism on dialysis.<ref>{{cite web |url=http://pi.amgen.com/united_states/sensipar/sensipar_pi_hcp_english.pdf |title=Sensipar: Highlights of Prescribing Information | publisher = Amgen Inc. |access-date=2014-10-29 |url-status=live |archive-url=https://web.archive.org/web/20141005071147/http://pi.amgen.com/united_states/sensipar/sensipar_pi_hcp_english.pdf |archive-date=2014-10-05 }}</ref><ref>{{cite journal | vauthors = Ott SM | title = Calcimimetics--new drugs with the potential to control hyperparathyroidism | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 83 | issue = 4 | pages = 1080–2 | date = April 1998 | doi = 10.1210/jcem.83.4.4799 | pmid = 9543121 | doi-access = free }}</ref> Treatment of secondary hyperparathyroidism with a calcimimetic in those on dialysis for CKD does not alter the risk of early death; however, it does decrease the likelihood of needing a parathyroidectomy.<ref name="Ballinger-2014"/> Treatment carries the risk of low blood calcium levels and [[vomiting]].<ref name="Ballinger-2014">{{cite journal | vauthors = Ballinger AE, Palmer SC, Nistor I, Craig JC, Strippoli GF | title = Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 12 | pages = CD006254 | date = 9 December 2014 | pmid = 25490118 | doi = 10.1002/14651858.CD006254.pub2 | pmc = 10614033 | doi-access = free }}</ref>

== Epidemiology ==
In the [[developed world]], between one and four per thousand people are affected.<ref name="Michels-2013">{{cite journal | vauthors = Michels TC, Kelly KM | title = Parathyroid disorders | journal = American Family Physician | volume = 88 | issue = 4 | pages = 249–57 | date = August 2013 | pmid = 23944728 }}</ref> Primary hyperparathyroidism is the most common type.<ref name="Fraser-2009" /> Certain exposures increase the risk of developing primary hyperparathyroidism such as sex and age. It occurs three times more often in women than men and is often diagnosed between the ages of 50 and 60 but is not uncommon before then.<ref name="NIDDK-2012" /> The disease was first described in the 1700s.<ref name="Gasparri-2015" /> In the late 1800s, it was determined to be related to the parathyroid.<ref name="Gasparri-2015" /> Surgery as a treatment was first carried out in 1925.<ref name="Gasparri-2015">{{cite book| vauthors = Gasparri G, Camandona M, Palestini N |title=Primary, Secondary and Tertiary Hyperparathyroidism: Diagnostic and Therapeutic Updates|date=2015|publisher=Springer|isbn=978-88-470-5758-6|url=https://books.google.com/books?id=T8MDCwAAQBAJ&pg=PA2|language=en|url-status=live|archive-url=https://web.archive.org/web/20170908183155/https://books.google.ca/books?id=T8MDCwAAQBAJ&pg=PA2|archive-date=2017-09-08}}</ref> The United States prevalence of primary hyperparathyroidism from 2010 was 233 per 100,000 women and 85 per 100,000 men. Black and white women aged 70–79 have the highest overall prevalence.<ref>{{cite journal |last1=Yeh |first1=Michael W. |last2=Ituarte |first2=Philip H. G. |last3=Zhou |first3=Hui Cynthia |last4=Nishimoto |first4=Stacie |last5=Amy Liu |first5=In-Lu |last6=Harari |first6=Avital |last7=Haigh |first7=Philip I. |last8=Adams |first8=Annette L. |title=Incidence and Prevalence of Primary Hyperparathyroidism in a Racially Mixed Population |journal=The Journal of Clinical Endocrinology & Metabolism |date=March 2013 |volume=98 |issue=3 |pages=1122–1129 |doi=10.1210/jc.2012-4022 |doi-access=free |pmid=23418315 |pmc=3590475 }}</ref> Secondary hyperparathyroidism is most commonly caused by [[chronic kidney disease]] and [[vitamin D deficiency]].<ref>{{cite journal |last1=Saliba |first1=W. |last2=El-Haddad |first2=B. |title=Secondary Hyperparathyroidism: Pathophysiology and Treatment |journal=The Journal of the American Board of Family Medicine |date=September 2009 |volume=22 |issue=5 |pages=574–581 |doi=10.3122/jabfm.2009.05.090026 |pmid=19734404 |doi-access=free }}</ref> The prevalence of vitamin D deficiency is about 50% of the world population and chronic kidney disease prevalence is 15% of the United States population.<ref name="van der Plas 271–278">{{Cite journal |last1=van der Plas |first1=W. Y. |last2=Noltes |first2=M. E. |last3=van Ginhoven |first3=T. M. |last4=Kruijff |first4=S. |date=December 2020 |title=Secondary and Tertiary Hyperparathyroidism: A Narrative Review |journal=Scandinavian Journal of Surgery |volume=109 |issue=4 |pages=271–278 |doi=10.1177/1457496919866015 |pmid=31364494 |doi-access=free }}</ref>

==History==
The oldest known case was found in a cadaver from an Early [[Neolithic]] cemetery in southwest Germany.<ref name="Zink-2005">{{cite journal | vauthors = Zink AR, Panzer S, Fesq-Martin M, Burger-Heinrich E, Wahl J, Nerlich AG | title = Evidence for a 7000-year-old case of primary hyperparathyroidism | journal = JAMA | volume = 293 | issue = 1 | pages = 40–2 | date = January 2005 | pmid = 15632333 | doi = 10.1001/jama.293.1.40-c }}</ref>

==Notes==
{{reflist|group=nb}}

== References ==
{{Reflist}}

== External links ==
* [http://www.endocrine.niddk.nih.gov/pubs/hyper/hyper.htm Overview] {{Webarchive|url=https://web.archive.org/web/20110524101254/http://www.endocrine.niddk.nih.gov/pubs/hyper/hyper.htm |date=2011-05-24 }} at [[Endocrine and Metabolic Diseases Information Service]]
* {{cite journal | vauthors = Insogna KL | title = Primary Hyperparathyroidism | journal = The New England Journal of Medicine | volume = 379 | issue = 11 | pages = 1050–1059 | date = September 2018 | pmid = 30207907 | doi = 10.1056/NEJMcp1714213 | type = Review }}
{{Parathyroid disease}}
{{Medical resources
|  DiseasesDB      = 20710
|  ICD11           = {{ICD11|5A51}}
|  ICD10           = {{ICD10|E21}}
|  ICD9            = {{ICD9|252.0}}
|  MedlinePlus     = 001215
|  eMedicineSubj   = emerg
|  eMedicineTopic  = 265
|  eMedicine_mult  = {{eMedicine2|med|3200}}
|  MeshID          = D006961
}}
{{Authority control}}

[[Category:Parathyroid disorders]]
[[Category:Endocrine-related cutaneous conditions]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Wikipedia neurology articles ready to translate]]