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Diabetesinsipidus
FromWikipedia,thefreeencyclopedia

Diabetesinsipidus(DI)isaconditioncharacterizedbyexcessivethirstandexcretionoflargeamountsof
severelydiluteurine,withreductionoffluidintakehavingnoeffectontheconcentrationoftheurine.[1]There
aredifferenttypesofDI,eachwithadifferentsetofcauses.Themostcommontypeinhumansisthe
neurologicalform,calledcentralDI(CDI),whichinvolvesadeficiencyofargininevasopressin(AVP),also
knownasantidiuretichormone(ADH).ThesecondcommontypeofDIisnephrogenicdiabetesinsipidus(NDI),
whichisduetokidneyornephrondysfunctioncausedbyaninsensitivityofthekidneysornephronstoADH.DI
canalsobegestational,orcausedbyalcoholorsometypesofdrugabuse.DIshouldnotbeconfusedwith
nocturia.

Diabetesinsipidus
pituitarydiabetesinsipidus

Althoughtheyhaveacommonname,diabetesmellitusanddiabetesinsipidusaretwoentirelyseparate
conditionswithunrelatedmechanisms.Bothcauselargeamountsofurinetobeproduced(polyuria).However,
diabetesinsipidusiseitheraproblemwiththeproductionofantidiuretichormone(centraldiabetesinsipidus)or
kidney'sresponsetoantidiuretichormone(nephrogenicdiabetesinsipidus),whereasdiabetesmellituscauses
polyuriaviaaprocesscalledosmoticdiuresis,duetothehighbloodsugarleakingintotheurineandtaking
excesswateralongwithit.
Thenumberofnewcasesofdiabetesinsipiduseachyearis3in100,000.[2]Diabetesinsipidususuallystartsin
childhoodorearlyadulthoodandaffectsmenmorecommonlythanwomen.[3]Theterm"diabetes"isderived
fromtheGreekwordmeaningsiphon.

Vasopressin
Classificationandexternalresources
Specialty

Endocrinology

ICD10

E23.2(http://apps.who.int/classificati
ons/icd10/browse/2016/en#/E23.2)
N25.1(http://apps.who.int/classificati
ons/icd10/browse/2016/en#/N25.1)

ICD9CM

253.5(http://www.icd9data.com/getI
CD9Code.ashx?icd9=253.5)588.1(ht
tp://www.icd9data.com/getICD9Cod
e.ashx?icd9=588.1)

OMIM

304800(http://omim.org/entry/30480
0)125800(http://omim.org/entry/125
800)

Contents
1
2
3
4

Signsandsymptoms
Diagnosis
Pathophysiology
Classification
4.1 Neurogenic
4.2 Nephrogenic
4.3 Dipsogenic
4.4 Gestational
5 Treatment
5.1 CentralDI
5.2 NephrogenicDI
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DiseasesDB 3639(http://www.diseasesdatabase.co
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5.2 NephrogenicDI
6 Etymology
7 References
8 Externallinks

Signsandsymptoms
Excessiveurinationandextremethirstandincreasedfluidintake(especiallyforcoldwaterandsometimesiceor
icewater)aretypicalforDI.[4]Thesymptomsofexcessiveurinationandextremethirstaresimilartowhatis
seeninuntreateddiabetesmellitus,withthedistinctionthattheurinedoesnotcontainglucose.Blurredvisionis
ararity.Signsofdehydrationmayalsoappearinsomeindividuals,sincethebodycannotconservemuch(ifany)
ofthewaterittakesin.
Extremeurinationcontinuesthroughoutthedayandthenight.Inchildren,DIcaninterferewithappetite,eating,
weightgain,andgrowth,aswell.Theymaypresentwithfever,vomiting,ordiarrhea.AdultswithuntreatedDI
mayremainhealthyfordecadesaslongasenoughwaterisconsumedtooffsettheurinarylosses.However,
thereisacontinuousriskofdehydrationandlossofpotassiumthatmayleadtohypokalemia.

Diagnosis

m/ddb3639.htm)
MedlinePlus 000377(http://www.nlm.nih.gov/me
dlineplus/ency/article/000377.htm)
Central000460(https://www.nlm.nih.
gov/medlineplus/ency/article/000460.
htm)
Congenital000461(https://www.nlm.n
ih.gov/medlineplus/ency/article/00046
1.htm)
Nephrogenic000511(https://www.nl
m.nih.gov/medlineplus/ency/article/00
0511.htm)
eMedicine

med/543(http://www.emedicine.com/
med/topic543.htm)ped/580(http://w
ww.emedicine.com/ped/topic580.htm
#)

MeSH

D003919(https://www.nlm.nih.gov/c
gi/mesh/2016/MB_cgi?field=uid&ter
m=D003919)

TodistinguishDIfromothercausesofexcessurination,bloodglucoselevels,bicarbonatelevels,andcalcium
levelsneedtobetested.Measurementofbloodelectrolytescanrevealahighsodiumlevel(hypernatremiaasdehydrationdevelops).Urinalysisdemonstratesa
diluteurinewithalowspecificgravity.Urineosmolarityandelectrolytelevelsaretypicallylow.
AfluiddeprivationtestisanotherwayofdistinguishingDIfromothercausesofexcessiveurination.ItisalsousedtohelpdeterminewhatDIiscausedby:
1.adefectinADHproduction
2.adefectinthekidneys'responsetoADH
Thistestmeasuresthechangesinbodyweight,urineoutput,andurinecompositionwhenfluidsarewithheldtoinducedehydration.Thebody'snormalresponseto
dehydrationistoconservewaterbyconcentratingtheurine.ThosewithDIcontinuetourinatelargeamountsofdiluteurineinspiteofwaterdeprivation.In
primarypolydipsia,theurineosmolalityshouldincreaseandstabilizeatabove280Osm/kgwithfluidrestriction,whileastabilizationatalowerlevelindicates
diabetesinsipidus.[5]Stabilizationinthistestmeans,morespecifically,whentheincreaseinurineosmolalityislessthan30Osm/kgperhourforatleastthree
hours.[5]SometimesmeasuringbloodlevelsofADHtowardtheendofthistestisalsonecessary,butismoretimeconsumingtoperform.[5]

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Todistinguishbetweenthemainforms,desmopressinstimulationisalsouseddesmopressincanbetakenbyinjection,anasalspray,oratablet.Whiletaking
desmopressin,apatientshoulddrinkfluidsorwateronlywhenthirstyandnotatothertimes,asthiscanleadtosuddenfluidaccumulationinthecentralnervous
system.Ifdesmopressinreducesurineoutputandincreasesurineosmolarity,thehypothalamicproductionofADHisdeficient,andthekidneyrespondsnormally
toexogenousvasopressin(desmopressin).IftheDIisduetorenalpathology,desmopressindoesnotchangeeitherurineoutputorosmolarity(sincethe
endogenousvasopressinlevelsarealreadyhigh).
Whilstdiabetesinsipidususuallyoccurswithpolydipsia,itcanalsorarelyoccurnotonlyintheabsenceofpolydipsiabutinthepresenceofitsopposite,adipsia
(orhypodipsia)."Adipsicdiabetesinsipidus"isrecognised[6]asamarkedabsenceofthirsteveninresponsetohyperosmolality.[7]InsomecasesofadipsicDI,the
patientmayalsofailtorespondtodesmopressin.[8]
IfcentralDIissuspected,testingofotherhormonesofthepituitary,aswellasmagneticresonanceimaging,particularlyapituitaryMRI,isnecessarytodiscover
ifadiseaseprocess(suchasaprolactinoma,orhistiocytosis,syphilis,tuberculosisorothertumororgranuloma)isaffectingpituitaryfunction.Mostpeoplewith
thisformhaveeitherexperiencedpastheadtraumaorhavestoppedADHproductionforanunknownreason.
Habitdrinking(initsseverestformtermedpsychogenicpolydipsia)isthemostcommonimitatorofdiabetesinsipidusatallages.Whilemanyadultcasesinthe
medicalliteratureareassociatedwithmentaldisorders,mostpatientswithhabitpolydipsiahavenootherdetectabledisease.Thedistinctionismadeduringthe
waterdeprivationtest,assomedegreeofurinaryconcentrationaboveisoosmolarisusuallyobtainedbeforethepatientbecomesdehydrated.

Pathophysiology
Electrolyteandvolumehomeostasisisacomplexmechanismthatbalancesthebody'srequirementsforbloodpressureandthemainelectrolytessodiumand
potassium.Ingeneral,electrolyteregulationprecedesvolumeregulation.Whenthevolumeisseverelydepleted,however,thebodywillretainwaterattheexpense
ofderangingelectrolytelevels.
Theregulationofurineproductionoccursinthehypothalamus,whichproducesADHinthesupraopticandparaventricularnuclei.Aftersynthesis,thehormoneis
transportedinneurosecretorygranulesdowntheaxonofthehypothalamicneurontotheposteriorlobeofthepituitarygland,whereitisstoredforlaterrelease.In
addition,thehypothalamusregulatesthesensationofthirstintheventromedialnucleusbysensingincreasesinserumosmolarityandrelayingthisinformationto
thecortex.
Neurogenic/centralDIresultsfromalackofADHoccasionallyitcanpresentwithdecreasedthirstasregulationofthirstandADHproductionoccurinclose
proximityinthehypothalamus.Itisencounteredasaresultofhypoxicencephalopathy,neurosurgery,autoimmunityorcancer,orsometimeswithoutan
underlyingcause(idiopathic).
Themaineffectororganforfluidhomeostasisisthekidney.ADHactsbyincreasingwaterpermeabilityinthecollectingductsanddistalconvolutedtubules
specifically,itactsonproteinscalledaquaporinsandmorespecificallyaquaporin2inthefollowingcascade.Whenreleased,ADHbindstoV2Gproteincoupled
receptorswithinthedistalconvolutedtubules,increasingcyclicAMP,whichcoupleswithproteinkinaseA,stimulatingtranslocationoftheaquaporin2channel
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storedinthecytoplasmofthedistalconvolutedtubulesandcollectingductsintotheapicalmembrane.Thesetranscribedchannelsallowwaterintothecollecting
ductcells.Theincreaseinpermeabilityallowsforreabsorptionofwaterintothebloodstream,thusconcentratingtheurine.
NephrogenicDIresultsfromlackofaquaporinchannelsinthedistalcollectingduct(decreasedsurfaceexpressionandtranscription).Itisseeninlithiumtoxicity,
hypercalcemia,hypokalemia,orreleaseofureteralobstruction.
Hereditaryformsofdiabetesinsipidusaccountforlessthan10%ofthecasesofdiabetesinsipidusseeninclinicalpractice.[9]

Classification
TheseveralformsofDIare:

Neurogenic
Neurogenicdiabetesinsipidus,morecommonlyknownascentraldiabetesinsipidus,isduetothelackofvasopressinproductioninthehypothalamusduetoa
rangeofcauses.TheunderlyingcausesofCentralDIcanincludevascular,autoimmune,infection,sarcoidosis,somedrugs,surgery,headtrauma,benignor
metastaticpituitaryhypothalamictumor(particularlyoriginatingfrombreastandlung),although50%ofcasesarefoundtobeidiopathic.

Nephrogenic
Nephrogenicdiabetesinsipidusisduetotheinabilityofthekidneytorespondnormallytovasopressin.

Dipsogenic
DipsogenicDIorprimarypolydipsiaresultsfromexcessiveintakeoffluidsasopposedtodeficiencyofargininevasopressin.Itmaybeduetoadefectordamage
tothethirstmechanism,locatedinthehypothalamus[10]orduetomentalillness.TreatmentwithDDAVPmayleadtowaterintoxication.

Gestational
GestationalDIoccursonlyduringpregnancyandthepostpartumperiod.Duringpregnancy,womenproducevasopressinaseintheplacenta,whichbreaksdown
ADH.GestationalDIisthoughttooccurwithexcessiveproductionand/orimpairedclearanceofvasopressinase.[11]
MostcasesofgestationalDIcanbetreatedwithdesmopressin(ddAVP),butnotvasopressin.Inrarecases,however,anabnormalityinthethirstmechanismcauses
gestationalDI,anddesmopressinshouldnotbeused.

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Diabetesinsipidusisalsoassociatedwithsomeseriousdiseasesofpregnancy,includingpreeclampsia,HELLPsyndromeandacutefattyliverofpregnancy.
ThesecauseDIbyimpairinghepaticclearanceofcirculatingvasopressinase.Itisimportanttoconsiderthesediseasesifawomanpresentswithdiabetesinsipidus
inpregnancy,becausetheirtreatmentsrequiredeliveryofthebabybeforethediseasewillimprove.Failuretotreatthesediseasespromptlycanleadtomaternalor
perinatalmortality.

Treatment
CentralDI
CentralDIandgestationalDIrespondtodesmopressinwhichisgivenasintranasalororaltablets.Carbamazepine,ananticonvulsivemedication,hasalsohad
somesuccessinthistypeofDI.Also,gestationalDItendstoabateonitsownfourtosixweeksfollowinglabor,thoughsomewomenmaydevelopitagainin
subsequentpregnancies.IndipsogenicDI,desmopressinisnotusuallyanoption.

NephrogenicDI
DesmopressinwillbeineffectiveinnephrogenicDIandistreatedbyreversingtheunderlyingcause(ifpossible)andreplacingthefreewaterdeficit.Thediuretic
hydrochlorothiazide(athiazidediuretic)orindomethacincanbeusedtocreatemildhypovolemiawhichencouragessaltandwateruptakeinproximaltubuleand
thusimprovenephrogenicdiabetesinsipidus.AmiloridehasadditionalbenefitofblockingLiuptake.Thiazidediureticsaresometimescombinedwithamilorideto
preventhypokalemia.Itseemsparadoxicaltotreatanextremediuresiswithadiuretic,andtheexactmechanismofactionisunknownbutthethiazidediuretics
willdecreasedistalconvolutedtubulereabsorptionofsodiumandwater,therebycausingdiuresis.Thisdecreasesplasmavolume,thusloweringtheglomerular
filtrationrateandenhancingtheabsorptionofsodiumandwaterintheproximalnephron.Lessfluidreachesthedistalnephron,sooverallfluidconservationis
obtained.[12]
LithiuminducednephrogenicDImaybeeffectivelymanagedwiththeadministrationofamiloride,apotassiumsparingdiureticoftenusedinconjunctionwith
thiazideorloopdiuretics.Clinicianshavebeenawareoflithiumtoxicityformanyyears,andtraditionallyhaveadministeredthiazidediureticsforlithiuminduced
polyuriaandnephrogenicdiabetesinsipidus.However,amiloridehasrecentlybeenshowntobeasuccessfultreatmentforthiscondition.[13]

Etymology
Theword"diabetes"(/da.bitiz/or/da.bits/)comesfromLatindiabts,whichinturncomesfromAncientGreek(diabts)whichliterally
means"apasserthroughasiphon".[14]AncientGreekphysicianAretaeusofCappadocia(fl.inthefirstcenturyCE)usedthatword,withtheintendedmeaning
"excessivedischargeofurine",asthenameforthedisease.[15][16]Ultimately,thewordcomesfromGreek(diabainein),meaning"topassthrough",[14]
whichiscomposedof(dia),meaning"through"and(bainein),meaning"togo".[15]Theword"diabetes"isfirstrecordedinEnglish,intheform
"diabete",inamedicaltextwrittenaround1425.
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"Insipidus"comesfromLatinlanguageinsipidus(tasteless),fromLatin:in"not"+sapidus"tasty"fromsapere"haveataste"thefullmeaningis"lacking
flavororzestnottasty".ApplicationofthisnametoDIarosefromthefactthatdiabetesinsipidusdoesnotcauseglycosuria(excretionofglucoseintotheurine).

References
1.Tamparo,Carol(2011).FifthEdition:DiseasesoftheHumanBody.Philadelphia,
PA:F.A.DavisCompany.p.288.ISBN9780803625051.
2.SaborioP,TiptonGA,ChanJC(2000)."DiabetesInsipidus".Pediatricsin
Review.21(4):122129.doi:10.1542/pir.214122.PMID10756175.
3.Tamparo,CarolLewis,Marcia(2011).DiseasesoftheHumanBody.
Philadelphia,PA:F.A.DavisCompany.p.289.ISBN9780803625051.
4.USE."DiabetesinsipidusPubMedHealth".Ncbi.nlm.nih.gov.Retrieved
20120528.
5.ElizabethDAgabegiAgabegi,StevenS.(2008).StepUptoMedicine(StepUp
Series).Hagerstwon,MD:LippincottWilliams&Wilkins.ISBN0781771536.
6.CrowleyRK,SherlockM,AghaA,SmithD,ThompsonCJ(2007)."Clinical
insightsintoadipsicdiabetesinsipidus:alargecaseseries".Clin.Endocrinol.
(Oxf).66(4):47582.doi:10.1111/j.13652265.2007.02754.x.PMID17371462.
7.SinhaA,BallS,JenkinsA,HaleJ,CheethamT(2011)."Objectiveassessmentof
thirstrecoveryinpatientswithadipsicdiabetesinsipidus".Pituitary.14(4):307
11.doi:10.1007/s1110201102943.PMID21301966.
8.SmithD,McKennaK,MooreK,TormeyW,FinucaneJ,PhillipsJ,BaylisP,
ThompsonCJ(2002)."Baroregulationofvasopressinreleaseinadipsicdiabetes
insipidus".J.Clin.Endocrinol.Metab.87(10):45648.doi:10.1210/jc.2002
020090.PMID12364435.

9.FujiwaraTM,BichetDG(2005)."MolecularBiologyofHereditaryDiabetes
Insipidus".JournaloftheAmericanSocietyofNephrology.16(10):28362846.
doi:10.1681/ASN.2005040371.PMID16093448.
10.PerkinsRM,YuanCM,WelchPG(March2006)."Dipsogenicdiabetesinsipidus:
reportofanoveltreatmentstrategyandliteraturereview".Clin.Exp.Nephrol.10
(1):637.doi:10.1007/s1015700503970.PMID16544179.
11.KaleliogluI,KubatUzumA,YildirimA,OzkanT,GungorF,HasR(2007).
"Transientgestationaldiabetesinsipidusdiagnosedinsuccessivepregnancies:
reviewofpathophysiology,diagnosis,treatment,andmanagementofdelivery".
Pituitary.10(1):8793.doi:10.1007/s1110200700061.PMID17308961.
12.LoffingJ(November2004)."Paradoxicalantidiureticeffectofthiazidesin
diabetesinsipidus:anotherpieceinthepuzzle".J.Am.Soc.Nephrol.15(11):
294850.doi:10.1097/01.ASN.0000146568.82353.04.PMID15504949.
13.FinchCK,KelleyKW,WilliamsRB(April2003)."Treatmentoflithiuminduced
diabetesinsipiduswithamiloride".Pharmacotherapy.23(4):54650.
doi:10.1592/phco.23.4.546.32121.PMID12680486.
14.OxfordEnglishDictionary.diabetes.Retrieved20110610.
15.Harper,Douglas(20012010)."OnlineEtymologyDictionary.diabetes.".
Retrieved20110610
16.Dallas,John(2011)."RoyalCollegeofPhysiciansofEdinburgh.Diabetes,
DoctorsandDogs:AnexhibitiononDiabetesandEndocrinologybytheCollege
Libraryforthe43rdSt.Andrew'sDayFestivalSymposium"

9.FujiwaraTM,BichetDG(2005)."MolecularBiologyofHereditaryDiabetes

Externallinks
Diabetesinsipidus(https://www.dmoz.org/Health/Conditions_and_Diseases/Endocrine_Disorders/Pituitary/Diabetes_Insipidus/)atDMOZ
Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Diabetes_insipidus&oldid=740509673"
Categories: Endocrinediseases Nephrology Rarediseases Thirst
Thispagewaslastmodifiedon21September2016,at14:23.
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