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Hypercalcaemia - Wikipedia, the free encyclopedia

Hypercalcaemia
FromWikipedia,thefreeencyclopedia

Hypercalcaemia(British English)orhypercalcemia (AmericanEnglish)isan elevatedcalcium(Ca2+)level intheblood.[1](Normal range:910.5mg/dLor2.2 2.6mmol/L).Itcanbean asymptomaticlaboratory finding,butbecausean elevatedcalciumlevelisoften indicativeofotherdiseases,a workupshouldbeundertaken ifitpersists.Itcanbedueto excessiveskeletalcalcium release,increasedintestinal calciumabsorption,or decreasedrenalcalcium excretion.

Hypercalcaemia
Classificationandexternalresources

Calcium ICD10 E83.5 (http://apps.who.int/classifications/icd10/browse/2010/en#/E83.5) 275.42(http://www.icd9data.com/getICD9Code.ashx? icd9=275.42)

ICD9

DiseasesDB 6196(http://www.diseasesdatabase.com/ddb6196.htm) MedlinePlus 000365 (http://www.nlm.nih.gov/medlineplus/ency/article/000365.htm) eMedicine med/1068(http://www.emedicine.com/med/topic1068.htm) emerg/260(http://www.emedicine.com/emerg/topic260.htm#) ped/1062(http://www.emedicine.com/ped/topic1062.htm#)

Contents

1Signsandsymptoms 2Causes D006934(http://www.nlm.nih.gov/cgi/mesh/2013/MB_cgi? MeSH 2.1Abnormal field=uid&term=D006934) parathyroid glandfunction 2.2Malignancy 2.3VitaminDmetabolicdisorders 2.4Disordersrelatedtohighboneturnoverrates 2.5Renalfailure 3Treatments 3.1Initialtherapy:fluidsanddiuretics 3.2Additionaltherapy:bisphosphonatesandcalcitonin 3.3Othertherapies 4Hypercalcaemiccrisis 5Seealso 6References

Signsandsymptoms

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Theneuromuscularsymptomsofhypercalcemiaarecausedbyanegativebathmotropiceffectduetothe increasedinteractionofcalciumwithsodiumchannels.Sincecalciumblockssodiumchannelsandinhibits depolarizationofnerveandmusclefibers,increasedcalciumraisesthethresholdfordepolarization.[2] Thereisageneralmnemonicforrememberingtheeffectsofhypercalcaemia:"Stones,Bones,Groans, ThronesandPsychiatricOvertones" Stones(renalorbiliary) Bones(bonepain) Groans(abdominalpain,nauseaandvomiting) Thrones(sitonthronepolyuria) Psychiatricovertones(Depression3040%,anxiety,cognitivedysfunction,insomnia,coma) Othersymptomscanincludefatigue,anorexia,andpancreatitis.[citationneeded] Abnormalheartrhythmscanresult,andECGfindingsofashortQTinterval[3]andawidenedTwave suggesthypercalcaemia.SignificanthypercalcaemiacancauseECGchangesmimickinganacute myocardialinfarction.[4]HypercalcaemiahasalsobeenknowntocauseanECGfindingmimicking hypothermia,knownasanOsbornwave.[5] Hypercalcaemiacanincreasegastrinproduction,leadingtoincreasedaciditysopepticulcersmayalso occur. Symptomsaremorecommonathighcalciumbloodvalues(12.0mg/dLor3mmol/l).Severe hypercalcaemia(above1516mg/dLor3.754mmol/l)isconsideredamedicalemergency:atthese levels,comaandcardiacarrestcanresult.Hypercalcaemiacausestheoppositethehighlevelsofcalcium ionsdecreaseneuronalexcitability,whichleadstohypotonicityofsmoothandstriatedmuscle.This explainsthefatigue,muscleweakness,lowtoneandsluggishreflexesinmusclegroups.Inthegutthis causesconstipation.Thesluggishnervesalsoexplaindrowsiness,confusion,hallucinations,stuporand/or coma.

Causes
Primaryhyperparathyroidismandmalignancyaccountforabout90%ofcasesofhypercalcaemia.[6][7]

Abnormalparathyroidglandfunction
primaryhyperparathyroidism solitaryparathyroidadenoma primaryparathyroidhyperplasia parathyroidcarcinoma multipleendocrineneoplasia(MEN) familialisolatedhyperparathyroidism[8] lithiumuse familialhypocalciurichypercalcaemia/familialbenignhypercalcaemia[9][10][11]

Malignancy

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solidtumourwithmetastasis(e.g.breastcanceror classicallysquamouscellcarcinoma,whichcanbePTHrP mediated) solidtumourwithhumoralmediationofhypercalcaemia (e.g.lungcancer,mostcommonlynonsmallcelllung cancer[12]orkidneycancer,phaeochromocytoma) haematologicmalignancy(multiplemyeloma,lymphoma, leukaemia) ovariansmallcellcarcinomaofthehypercalcemictype

VitaminDmetabolicdisorders

Micrographofovariansmallcell carcinomaofthehypercalcemictype. H&Estain.

hypervitaminosisD(vitaminDintoxication) elevated1,25(OH)2D(seecalcitriolunderVitaminD)levels(e.g.sarcoidosisandother granulomatousdiseases) idiopathichypercalcaemiaofinfancy[13] reboundhypercalcaemiaafterrhabdomyolysis

Disordersrelatedtohighboneturnoverrates
hyperthyroidism prolongedimmobilization thiazideuse vitaminAintoxication multiplemyeloma

Renalfailure
severesecondaryhyperparathyroidism aluminiumintoxication milkalkalisyndrome

Treatments
Thegoaloftherapyistotreatthehypercalcaemiafirstandsubsequentlyeffortisdirectedtotreatthe underlyingcause.

Initialtherapy:fluidsanddiuretics
hydration,increasingsaltintake,andforceddiuresis. hydrationisneededbecausemanypatientsaredehydratedduetovomitingorrenaldefectsin concentratingurine. increasedsaltintakealsocanincreasebodyfluidvolumeaswellasincreasingurinesodium excretion,whichfurtherincreasesurinarycalciumexcretion(Inotherwords,calciumand sodium(salt)arehandledinasimilarwaybythekidney.Anythingthatcausesincreased sodium(salt)excretionbythekidneywill,enpassant,causeincreasedcalciumexcretionby

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thekidney) afterrehydration,aloopdiureticsuchasfurosemidecanbegiventopermitcontinuedlarge volumeintravenoussaltandwaterreplacementwhileminimizingtheriskofbloodvolume overloadandpulmonaryoedema.Inaddition,loopdiureticstendtodepressrenalcalcium reabsorptiontherebyhelpingtolowerbloodcalciumlevels canusuallydecreaseserumcalciumby13mg/dLwithin24h cautionmustbetakentopreventpotassiumormagnesiumdepletion

Additionaltherapy:bisphosphonatesandcalcitonin
bisphosphonatesarepyrophosphateanalogueswithhighaffinityforbone,especiallyareasofhigh boneturnover. theyaretakenupbyosteoclastsandinhibitosteoclasticboneresorption currentavailabledrugsinclude(inorderofpotency):(1stgen)etidronate,(2ndgen) tiludronate,IVpamidronate,alendronate(3rdgen)zoledronateandrisedronate allpatientswithcancerassociatedhypercalcaemiashouldreceivetreatmentwith bisphosphonatessincethe'firstline'therapy(above)cannotbecontinuedindefinitelynorisit withoutrisk.Further,evenifthe'firstline'therapyhasbeeneffective,itisavirtualcertainty thatthehypercalcaemiawillrecurinthepatientwithhypercalcaemiaofmalignancy.Useof bisphosphonatesinsuchcircumstances,then,becomesboththerapeuticandpreventative patientsinrenalfailureandhypercalcaemiashouldhaveariskbenefitanalysisbeforebeing givenbisphosphonates,sincetheyarerelativelycontraindicatedinrenalfailure. Calcitoninblocksboneresorptionandalsoincreasesurinarycalciumexcretionbyinhibitingrenal calciumreabsorption Usuallyusedinlifethreateninghypercalcaemiaalongwithrehydration,diuresis,and bisphosphonates Helpspreventrecurrenceofhypercalcaemia Doseis4Unitsperkgviasubcutaneousorintramuscularrouteevery12hours,usuallynot continuedindefinitely

Othertherapies
rarelyused,orusedinspecialcircumstances plicamycininhibitsboneresorption(rarelyused) galliumnitrateinhibitsboneresorptionandchangesstructureofbonecrystals(rarelyused) glucocorticoidsincreaseurinarycalciumexcretionanddecreaseintestinalcalciumabsorption noeffectoncalciumlevelinnormalorprimaryhyperparathyroidism effectiveinhypercalcaemiaduetoosteolyticmalignancies(multiplemyeloma, leukaemia,Hodgkin'slymphoma,carcinomaofthebreast)duetoantitumourproperties alsoeffectiveinhypervitaminosisDandsarcoidosis dialysisusuallyusedinseverehypercalcaemiacomplicatedbyrenalfailure.Supplemental phosphateshouldbemonitoredandaddedifnecessary phosphatetherapycancorrectthehypophosphataemiainthefaceofhypercalcaemiaand lowerserumcalcium

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Hypercalcaemiccrisis
Ahypercalcaemiccrisisisanemergencysituationwithaseverehypercalcaemia,generallyabove approximately14mg/dL(or3.5mmol/l).[14] Themainsymptomsofahypercalcaemiccrisisareoliguriaoranuria,aswellassomnolenceorcoma.[15] Afterrecognition,primaryhyperparathyroidismshouldbeprovedorexcluded.[15] Inextremecasesofprimaryhyperparathyroidism,removaloftheparathyroidglandaftersurgicalneck explorationistheonlywaytoavoiddeath.[15]Thediagnosticprogramshouldbeperformedwithinhours, inparallelwithmeasurestolowerserumcalcium.[15]Treatmentofchoiceforacutelyloweringcalciumis extensivehydrationandcalcitonin,aswellasbisphosphonates(whichhaveeffectoncalciumlevelsafter oneortwodays).[16]

Seealso
Calciummetabolism Dent'sDisease Hypocalcaemia Electrolytedisturbance Disordersofcalciummetabolism ATCcodeV03#V03AGDrugsfortreatmentofhypercalcemia CYP24A1couldplayaroleinsevereinfantilehypercalcaemia.[17]

References
1. ^"hypercalcemia (http://web.archive.org/web/20090616022448/http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp ?pg=/ppdocs/us/common/dorlands/dorland/four/000050805.htm) "at Dorland'sMedicalDictionary 2. ^Armstrong,C.M.,Cota,Gabriel.Cota(1999)."CalciumblockofNa+channelsanditseffectonclosing rate"(//www.ncbi.nlm.nih.gov/pmc/articles/PMC22436) . ProceedingsoftheNationalAcademyofSciences oftheUnitedStatesofAmerica 96(7):41544157.Bibcode:1999PNAS...96.4154A (http://adsabs.harvard.edu/abs/1999PNAS...96.4154A) .doi:10.1073/pnas.96.7.4154 (http://dx.doi.org/10.1073%2Fpnas.96.7.4154) .PMC22436 (//www.ncbi.nlm.nih.gov/pmc/articles/PMC22436) . 3. ^http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/hypercalcemia/ 4. ^Wesson,L.Suresh,V.Parry,R.(2009)."Severehypercalcaemiamimickingacutemyocardialinfarction". Clinicalmedicine(London,England) 9(2):186187.doi:10.7861/clinmedicine.92186 (http://dx.doi.org/10.7861%2Fclinmedicine.92186) .PMID19435131 (//www.ncbi.nlm.nih.gov/pubmed/19435131) . 5. ^SerafiS,VliekC,TaremiM(2011)"Osbornwavesinahypothermicpatient"TheJournalofCommunity HospitalInternalMedicinePerspectiveshttp://www.jchimp.net/index.php/jchimp/article/view/10742/html 6. ^Table204in:Mitchell,RichardSheppardKumar,VinayAbbas,AbulK.Fausto,Nelson. RobbinsBasic Pathology.Philadelphia:Saunders.ISBN1416029737.8thedition. 7. ^Tierney,LawrenceM.McPhee,StephenJ.Papadakis,MaxineA.(2006). CurrentMedicalDiagnosisand Treatment2007(CurrentMedicalDiagnosisandTreatment).McGrawHillProfessional.p.901.ISBN007 1472479. 8. ^Online'MendelianInheritanceinMan'(OMIM)146200(http://omim.org/entry/146200) 9. ^Online'MendelianInheritanceinMan'(OMIM)145980(http://omim.org/entry/145980)

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10. ^Online'MendelianInheritanceinMan'(OMIM)145981(http://omim.org/entry/145981) 11. ^Online'MendelianInheritanceinMan'(OMIM)600740(http://omim.org/entry/600740) 12. ^NonSmallCellLungCancer(http://emedicine.medscape.com/article/279960overview#a0104) at medscape.Author:WinstonWTan.ChiefEditor:JulesEHarris.Updated:Mar30,2011 13. ^Online'MendelianInheritanceinMan'(OMIM)143880(http://omim.org/entry/143880) 14. ^HypercalcemiainEmergencyMedicine(http://emedicine.medscape.com/article/766373overview) at Medscape.Author:RobinRHemphill.ChiefEditor:ErikDSchraga.RetrievedApril2011 15. ^ a b c dZieglerR(February2001)."Hypercalcemiccrisis". J.Am.Soc.Nephrol.12Suppl17:S39. PMID11251025(//www.ncbi.nlm.nih.gov/pubmed/11251025) . 16. ^Page394(http://books.google.se/books?id=LngD6RFXY_AC&pg=PA394) in:Roenn,JamieH.Von AnnBergerShuster,JohnW.(2007). Principlesandpracticeofpalliativecareandsupportiveoncology. Hagerstwon,MD:LippincottWilliams&Wilkins.ISBN0781795958. 17. ^Dauber,AndrewNguyenThutrangT,SochettEtienne,ColeDavidEC,HorstRonald,AbramsStevenA, CarpenterThomasO,HirschhornJoelN(Nov.2011)."GeneticDefectinCYP24A1,theVitaminD24 HydroxylaseGene,inaPatientwithSevereInfantileHypercalcemia" (//www.ncbi.nlm.nih.gov/pmc/articles/PMC3275367) . TheJournalofClinicalEndocrinologyand Metabolism(inENG) 97(2):E26874.doi:10.1210/jc.20111972(http://dx.doi.org/10.1210%2Fjc.2011 1972) .PMC3275367(//www.ncbi.nlm.nih.gov/pmc/articles/PMC3275367) .PMID22112808 (//www.ncbi.nlm.nih.gov/pubmed/22112808) .

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