3/4/2016

SyndromeofInappropriateAntidiureticHormoneSecretion:PracticeEssentials,Background,Pathophysiology

SyndromeofInappropriateAntidiureticHormone
Secretion
Author:ChristiePThomas,MBBS,FRCP,FASN,FAHAChiefEditor:VecihiBatuman,MD,FACP,FASN
more...
Updated:Oct28,2015

PracticeEssentials
Thesyndromeofinappropriateantidiuretichormone(ADH)secretion(SIADH)is
definedbythehyponatremiaandhypoosmolalityresultingfrominappropriate,
continuedsecretionoractionofthehormonedespitenormalorincreasedplasma
volume,whichresultsinimpairedwaterexcretion.Thekeytounderstandingthe
pathophysiology,signs,symptoms,andtreatmentofSIADHistheawarenessthat
thehyponatremiaresultsfromanexcessofwaterratherthanadeficiencyof
sodium.

Signsandsymptoms
Dependingonthemagnitudeandrateofdevelopment,hyponatremiamayormay
notcausesymptoms.Thehistoryshouldtakeintoaccountthefollowing
considerations:
Ingeneral,slowlyprogressivehyponatremiaisassociatedwithfewer
symptomsthanisarapiddropofserumsodiumtothesamevalue
Signsandsymptomsofacutehyponatremiadonotpreciselycorrelatewith
theseverityortheacuityofthehyponatremia
PatientsmayhavesymptomsthatsuggestincreasedsecretionofADH,such
aschronicpain,symptomsfromcentralnervoussystemorpulmonarytumors
orheadinjury,ordruguse
Sourcesofexcessivefluidintakeshouldbeevaluated
Thechronicityoftheconditionshouldbeconsidered
Aftertheidentificationofhyponatremia,theapproachtothepatientdependsonthe
clinicallyassessedvolumestatus.Prominentphysicalfindingsmaybeseenonlyin
severeorrapidonsethyponatremiaandcanincludethefollowing:
Confusion,disorientation,delirium
Generalizedmuscleweakness,myoclonus,tremor,asterixis,hyporeflexia,
ataxia,dysarthria,CheyneStokesrespiration,pathologicreflexes
Generalizedseizures,coma
SeePresentationformoredetail.

Diagnosis
Intheabsenceofasinglelaboratorytesttoconfirmthediagnosis,SIADHisbest
definedbytheclassicBartterSchwartzcriteria,whichcanbesummarizedas
follows[1]:
Hyponatremiawithcorrespondinghypoosmolality
Continuedrenalexcretionofsodium
Urinelessthanmaximallydilute
Absenceofclinicalevidenceofvolumedepletion
Absenceofothercausesofhyponatremia
Correctionofhyponatremiabyfluidrestriction
ThefollowinglaboratorytestsmaybehelpfulinthediagnosisofSIADH:
Serumsodium,potassium,chloride,andbicarbonate
Plasmaosmolality
Serumcreatinine
Bloodureanitrogen
Bloodglucose
Urineosmolality
Serumuricacid
Serumcortisol
Thyroidstimulatinghormone
Thepatientsvolumeshouldbeassessedclinicallytohelpruleoutthepresenceof
hypovolemia.
Imagingstudiesthatmaybeconsideredincludethefollowing:
Chestradiography(fordetectionofanunderlyingpulmonarycauseof
SIADH)
Computedtomographyormagneticresonanceimagingofthehead(for
detectionofcerebraledemaoccurringasacomplicationofSIADH,for

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SyndromeofInappropriateAntidiureticHormoneSecretion:PracticeEssentials,Background,Pathophysiology

identificationofaCNSdisorderresponsibleforSIADH,orforhelpingtorule
outotherpotentialcausesofachangeinneurologicstatus)
SeeWorkupformoredetail.

Management
TreatmentofSIADHandtherapidityofcorrectionofhyponatremiadependonthe
following:
Degreeofhyponatremia
Whetherthepatientissymptomatic
Whetherthesyndromeisacute(<48hours)orchronic
Urineosmolalityandcreatinineclearance
Ifthedurationofhyponatremiaisunknownandthepatientisasymptomatic,itis
reasonabletopresumechronicSIADH.Diagnosisandtreatmentoftheunderlying
causeofSIADHarealsoimportant.
Inanemergencysetting,aggressivetreatmentofhyponatremiashouldalwaysbe
weighedagainsttheriskofinducingcentralpontinemyelinolysis(CMP).Such
treatmentiswarrantedasfollows:
Indicatedinpatientswhohaveseveresymptoms(eg,seizures,stupor,coma,
andrespiratoryarrest),regardlessofthedegreeofhyponatremia
Stronglyconsideredforthosewhohavemoderatetoseverehyponatremia
withadocumenteddurationoflessthan48hours
Thegoalistocorrecthyponatremiaataratethatdoesnotcauseneurologic
complications,asfollows:
Raiseserumsodiumby0.51mEq/hr,andnotmorethan1012mEqinthe
first24hours
Aimatmaximumserumsodiumof125130mEq/L
Inanacutesetting(<48hourssinceonset)wheremoderatesymptomsarenoted,
treatmentoptionsforhyponatremiaincludethefollowing:
3%hypertonicsaline(513mEq/L)
Loopdiureticswithsaline
Vasopressin2receptorantagonists(aquaretics,suchasconivaptan)
Waterrestriction
Inachronicasymptomaticsetting,theprincipaloptionsareasfollows:
Fluidrestriction
Vassopressin2receptorantagonists
Ifvasopressin2receptorantagonistsareunavailableoriflocalexperience
withthemislimited,otheragentstobeconsideredincludeloopdiureticswith
increasedsaltintake,urea,mannitol,anddemeclocycline
SeeTreatmentandMedicationformoredetail.

ContributorInformationandDisclosures
Author
ChristiePThomas,MBBS,FRCP,FASN,FAHAProfessor,DepartmentofInternalMedicine,Divisionof
Nephrology,DepartmentsofPediatricsandObstetricsandGynecology,MedicalDirector,Kidneyand
Kidney/PancreasTransplantProgram,UniversityofIowaHospitalsandClinics
ChristiePThomas,MBBS,FRCP,FASN,FAHAisamemberofthefollowingmedicalsocieties:American
CollegeofPhysicians,AmericanHeartAssociation,AmericanSocietyofNephrology,RoyalCollegeof
Physicians
Disclosure:Nothingtodisclose.
Coauthor(s)
MonyFraer,MD,FACP,FASNAssociateProfessor,DivisionofNephrology,DepartmentofMedicine,University
ofIowaHospitalsandClinicsStaffPhysician,IowaCityVeteransAffairsMedicalCenter
Disclosure:Nothingtodisclose.
SpecialtyEditorBoard
EleanorLederer,MDProfessorofMedicine,Chief,NephrologyDivision,Director,NephrologyTrainingProgram,
Director,MetabolicStoneClinic,KidneyDiseaseProgram,UniversityofLouisvilleSchoolofMedicineConsulting
Staff,LouisvilleVeteransAffairsHospital
EleanorLederer,MDisamemberofthefollowingmedicalsocieties:AmericanAssociationfortheAdvancement
ofScience,InternationalSocietyofNephrology,AmericanSocietyforBiochemistryandMolecularBiology,
AmericanFederationforMedicalResearch,AmericanSocietyforBoneandMineralResearch,AmericanSociety
ofNephrology,AmericanSocietyofTransplantation,KentuckyMedicalAssociation,NationalKidneyFoundation,
PhiBetaKappa
Disclosure:Receivedgrant/researchfundsfromDeptofVeteransAffairsforresearchReceivedsalaryfrom
AmericanSocietyofNephrologyforasncouncilpositionReceivedsalaryfromUniversityofLouisvillefor
employmentReceivedsalaryfromUniversityofLouisvillePhysiciansforemploymentReceivedcontract
paymentfromAmericanPhysicianInstituteforAdvancedProfessionalStudies,LLCforindependentcontractor
ReceivedcontractpaymentfromHealthcareQualityStrategies,Incforindependentcont.

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SyndromeofInappropriateAntidiureticHormoneSecretion:PracticeEssentials,Background,Pathophysiology

ChiefEditor
VecihiBatuman,MD,FACP,FASNHuberwaldProfessorofMedicine,SectionofNephrologyHypertension,
TulaneUniversitySchoolofMedicineChief,RenalSection,SoutheastLouisianaVeteransHealthCareSystem
VecihiBatuman,MD,FACP,FASNisamemberofthefollowingmedicalsocieties:AmericanCollegeof
Physicians,AmericanSocietyofHypertension,AmericanSocietyofNephrology,InternationalSocietyof
Nephrology
Disclosure:Nothingtodisclose.
Acknowledgements
HowardABessen,MDProfessorofMedicine,DepartmentofEmergencyMedicine,UCLASchoolofMedicine
ProgramDirector,HarborUCLAMedicalCenter
HowardABessen,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeofEmergency
Physicians
Disclosure:Nothingtodisclose.
KeenanBora,MDFellow,MedicalToxicology,DetroitMedicalCenterAttendingPhysician,MedicalCenter
EmergencyServices,Detroit
KeenanBora,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofClinicalToxicology,
AmericanAcademyofEmergencyMedicine,AmericanCollegeofEmergencyPhysicians,AmericanCollegeof
MedicalToxicology,andAmericanMedicalAssociation
Disclosure:Nothingtodisclose.
MeherChaudhry,MDChiefResident,DepartmentofEmergencyMedicine,DetroitReceivingHospital,
UniversityHealthCenter
Disclosure:Nothingtodisclose.
SonaliDeshmukh,MBBSConsultingStaff,OmahaNephrology,Nebraska
SonaliDeshmukh,MBBSisamemberofthefollowingmedicalsocieties:AmericanSocietyofNephrology
Disclosure:Nothingtodisclose.
RobertJFerryJr,MDChief,DivisionofPediatricEndocrinologyandMetabolism,LeBonheurChildren's
HospitalProfessor,DepartmentofPediatrics,UniversityofTennesseeHealthScienceCenteratMemphisSt.
JudeChildren'sResearchHospital,Memphis,TNBrigadeSurgeon,36thSustainmentBrigade,U.S.Army
AdjunctProfessor,PediatricSurgeryDepartment,KingSaudUniversity,Riyadh,SaudiArabia
RobertJFerryJr,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofPediatrics,
AmericanDiabetesAssociation,AmericanMedicalAssociation,EndocrineSociety,LawsonWilkinsPediatric
EndocrineSociety,SocietyforPediatricResearch,andTexasPediatricSociety
Disclosure:NutropinSpeakersBureauHonorariaSpeakingandteachingGenotropinSpeakersBureauHonoraria
SpeakingandteachingEliLilly&Co.Grant/researchfundsInvestigatorMacroGenics,Inc.Grant/researchfunds
InvestigatorIpsen,S.A.(formerlyTercica,Inc.)Grant/researchfundsInvestigatorNovoNordiskSA
Grant/researchfundsInvestigatorDiamydInvestigator
StephenKemp,MD,PhDProfessor,DepartmentofPediatrics,SectionofPediatricEndocrinology,Universityof
ArkansasCollegeofMedicineandArkansasChildren'sHospital
StephenKemp,MD,PhDisamemberofthefollowingmedicalsocieties:AmericanAcademyofPediatrics,
AmericanAssociationofClinicalEndocrinologists,AmericanPediatricSociety,EndocrineSociety,PhiBeta
Kappa,SouthernMedicalAssociation,andSouthernSocietyforPediatricResearch
Disclosure:Nothingtodisclose.
EleanorLederer,MDProfessorofMedicine,Chief,NephrologyDivision,Director,NephrologyTrainingProgram,
Director,MetabolicStoneClinic,KidneyDiseaseProgram,UniversityofLouisvilleSchoolofMedicineConsulting
Staff,LouisvilleVeteransAffairsHospital
EleanorLederer,MDisamemberofthefollowingmedicalsocieties:AmericanAssociationfortheAdvancement
ofScience,AmericanFederationforMedicalResearch,AmericanSocietyforBiochemistryandMolecular
Biology,AmericanSocietyforBoneandMineralResearch,AmericanSocietyofNephrology,AmericanSociety
ofTransplantation,InternationalSocietyofNephrology,KentuckyMedicalAssociation,NationalKidney
Foundation,andPhiBetaKappa
Disclosure:DeptofVeteransAffairsGrant/researchfundsResearch
LynneLiptonLevitsky,MDChief,PediatricEndocrineUnit,MassachusettsGeneralHospitalAssociate
ProfessorofPediatrics,HarvardMedicalSchool
LynneLiptonLevitsky,MDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,American
AcademyofPediatrics,AmericanDiabetesAssociation,AmericanPediatricSociety,EndocrineSociety,Lawson
WilkinsPediatricEndocrineSociety,andSocietyforPediatricResearch
Disclosure:PfizerGrant/researchfundsP.I.TercicaGrant/researchfundsOtherEliLilyGrant/researchfunds
PINovoNordiskGrant/researchfundsPI
ChikeMagnusNzerue,MDAssociateDeanforClinicalAffairs,ViceChairmanofInternalMedicine,Meharry
MedicalCollege
ChikeMagnusNzerue,MDisamemberofthefollowingmedicalsocieties:AmericanAssociationforthe
AdvancementofScience,AmericanCollegeofPhysicians,AmericanCollegeofPhysiciansAmericanSocietyof
InternalMedicine,AmericanSocietyofNephrology,andNationalKidneyFoundation

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SyndromeofInappropriateAntidiureticHormoneSecretion:PracticeEssentials,Background,Pathophysiology

Disclosure:Nothingtodisclose.
JoseFPascualyBaralt,MDChief,DivisionofPediatricNephrology,SanAntonioMilitaryPediatricCenter
ClinicalProfessor,DepartmentofPediatrics,UniversityofTexasHealthScienceCampus
JoseFPascualyBaralt,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofPediatrics,
AmericanSocietyofNephrology,AmericanSocietyofPediatricNephrology,AssociationofMilitarySurgeonsof
theUS,andInternationalSocietyofNephrology
Disclosure:Nothingtodisclose.
AlexandrRafailov,MDStaffPhysician,DepartmentofEmergencyMedicine,StateUniversityofNewYork
Downstate/KingsCountyHospital
Disclosure:Nothingtodisclose.
ArlanLRosenbloom,MDAdjunctDistinguishedServiceProfessorEmeritusofPediatrics,UniversityofFlorida
FellowoftheAmericanAcademyofPediatricsFellowoftheAmericanCollegeofEpidemiology
ArlanLRosenbloom,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofPediatrics,
AmericanCollegeofEpidemiology,AmericanPediatricSociety,EndocrineSociety,FloridaPediatricSociety,
LawsonWilkinsPediatricEndocrineSociety,andSocietyforPediatricResearch
Disclosure:Nothingtodisclose.
ErikDSchraga,MDConsultingStaff,DepartmentofEmergencyMedicine,MillsPeninsulaEmergencyMedical
AssociatesConsultingStaff,PermanenteMedicalGroup,KaiserPermanente,SantaClaraMedicalCenter
Disclosure:Nothingtodisclose.
RichardHSinert,DOAssociateProfessorofEmergencyMedicine,ClinicalAssistantProfessorofMedicine,
ResearchDirector,StateUniversityofNewYorkCollegeofMedicineConsultingStaff,Departmentof
EmergencyMedicine,KingsCountyHospitalCenter
RichardHSinert,DOisamemberofthefollowingmedicalsocieties:AmericanCollegeofPhysiciansand
SocietyforAcademicEmergencyMedicine
Disclosure:Nothingtodisclose.
FranciscoTalavera,PharmD,PhDAdjunctAssistantProfessor,UniversityofNebraskaMedicalCenterCollege
ofPharmacyEditorinChief,MedscapeDrugReference
Disclosure:MedscapeSalaryEmployment
MaryLWindle,PharmDAdjunctAssociateProfessor,UniversityofNebraskaMedicalCenterCollegeof
PharmacyPharmacyEditor,Medscape
Disclosure:Nothingtodisclose.

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