腎上腺意外瘤指南課件

腎上腺意外瘤指南腎上腺意外瘤指南1（優(yōu)選）腎上腺意外瘤指南（優(yōu)選）腎上腺意外瘤指南2Definition“Masslesiongreaterthan1cmindiameterdiscovered“accidentally”duringaradiographicexaminationperformedforindicationsotherthananevaluationforadrenaldisease.”Managementoftheclinicallyinapparentadrenalmass(incidentaloma).NIHState-of-the-ScienceConferenceStatementFeb4-6,2002.Definition“Masslesiongreater3PrevalenceAutopsies:87,065cases:6%withadrenaladenomasAbdominalCT(61,054CTscansreviewed):4%withadrenaladenomasNowapproachesthe8.7%incidencereportedinautopsyseries

PrevalenceAutopsies:87,065ca4IncidenceIncreaseswithAgeEndocrineandMetabolismClinicsofNorthAmerica.2000;29(1):159-185IncidenceIncreaseswithAgeEn5ThreeMainQuestionsIstheadrenalmasshormonallyactive?Isthemassbenignormalignant?Doesthepatienthaveahistoryof apreviousmalignantlesion? Isitmetastatic?ThreeMainQuestionsIstheadr6AnatomyAnatomy7AnatomyAnatomy8AnatomyPrimaryAldosteronismCushing’sSyndromeDHEA-sPheochromocytomaAnatomyPrimaryAldosteronismCu9FrequencyofFindingsMulticenterstudyof1096casesNonfunctioningadenoma:85%SubclinicalCushing’ssyndrome:9%Pheochromocytoma:4%Aldosteronomas:2%Manteroetal.85(2):637.(2000)

FrequencyofFindingsMulticent10Pheochromocytoma5%AsummaryoftheliteratureWhenthetestisnegative,noothertestsareneeded.IncidenceIncreaseswithAgeSexhormonesecretingadrenocorticaltumorsIncidenceIncreaseswithAgeTypicallyoccurinthepresenceofclinicalmanifestations(hirsutismorvirilization)Veryrare:5casesper1millionpopulationAbdominalCT(61,054CTscansreviewed):4%withadrenaladenomas1976%ofpheoareundiagnoseduntilafterdeathSurgery1991Dec;110(6):101421MostcommonprimaryEquallyeffectiveasCTImagingPhenotype(features)Plasmaaldosteroneconcentrationandplasmaaldosteroneconcentration/plasmareninactivityratio(PAC/PRA).ImagePhenotypeCTScanFrequencyofFindingsAllolio,B.,AdrenalIncidentalomas.AdrenalDisorders,ed.C.G.MargiorisAN.2001,Totowa:HumanaPressInc.Pheochromocytoma5%Frequency11AsummaryoftheliteratureNonfunctioningadenomaApproximately80% SubclinicalCushingsyndrome(SCS),5%Pheochromocytoma5% Aldosteronoma1%adrenocorticalcarcinoma(ACC)<5%Metastaticlesion2.5%Ganglioneuromas,myelolipomas,orbenigncysts AsummaryoftheliteratureNon12考慮是否手術(shù)治療之前準確的功能診斷非常必要嗜鉻細胞瘤要進行認真的術(shù)前準備以避免術(shù)中和術(shù)后的發(fā)作和死亡。原發(fā)性醛固酮增多癥的患者需要明確是否存在腎上腺皮質(zhì)增生及無功能的腎上腺腺瘤。腎上腺源性Cushing綜合征的患者在行切除術(shù)后可能發(fā)生腎上腺皮質(zhì)功能不全，激素的替代以及增減治療需要非常仔細。亞臨床Cushing綜合征的患者是否需要手術(shù)治療仍存在爭議。腎上腺皮質(zhì)癌的患者手術(shù)前需要外科醫(yī)師和內(nèi)分泌科醫(yī)師或腫瘤科醫(yī)師共同協(xié)商決定切除的方式，因為首次切除的效果是生存率的主要預(yù)測因素。超過4cm的腎上腺無功能瘤可以考慮切除。小的髓脂肪瘤或良性的囊腫一般影像學(xué)檢查即可確診，通常不需要治療，除非有癥狀可以考慮手術(shù)治療。考慮是否手術(shù)治療之前準確的功能診斷非常必要嗜鉻細胞瘤要進行13Algorithmfortheevaluationandmanagementofanadrenalincidentaloma*Reimagein3to6monthsandannuallyfor1to2years;repeatfunctionalstudiesannually for5years.Ifmassgrowsmorethan1cmorbecomeshormonallyactive,thenadrenalectomyisrecommended.Algorithmfortheevaluationa14HyperfunctioningHormonalEvaluationSubclinicalCushing’sSyndromePheochromocytomaPrimaryAldosteronismSexhormonesecretingadrenocorticaltumorsHyperfunctioningHormonalEval15SubclinicalCushing’sSyndromeHypercortisolismwithoutclinicalmanifestationsofCushing’ssyndromeMostfrequenthormonalabnormalityinadrenalincidentalomasSubclinicalCushing’sSyndrome16SubclinicalCushing’sSyndrome2000;29(1):159-185monitoringPurplestriaeProbabilityofmalignancyincreaseswithsizeWhattodo?SexhormonesecretingadrenocorticaltumorsLiteratureSupportsSubclinicalCushing’ssyndrome:9%AdrenalDisorders,ed.IncidenceIncreaseswithAgeMayoClinicStudyPheochromocytomaMass<4cmcanbemonitoredPatientwithKnownMalignancyHyperfunctioningHormonalEvaluation1040%ofpatientswithknownmalignancyhaveadrenalmetastasesatautopsyMayoClinicStudyOsteoporosis?SubclinicalCushing’sSyndromeCentralobesityFacialroundingBuffalohumpEasybruisingPurplestriaeProximalmuscleweaknessEmotional/cognitivechangesSubclinicalCushing’sSyndrome17SubclinicalCushing’sSyndromeIncreaseriskfor:HypertensionDyslipidemiaImpairedglucosetoleranceType2DMAtherosclerosisOsteoporosis?TauchmanovaL,et.al.PatientswithsubclinicalCushing’ssyndromeduetoadrenaladenomahaveincreasecardiovascularrisk.JCEM2000;85:1440.SubclinicalCushing’sSyndrome18SubclinicalCushing’sSyndromeBiochemicalabnormalitiesElevatedurinefreecortisolLoworsuppressedACTHBlunteddiurnalvariationNocortisolsuppressionafter1mgovernightdexamethasonesuppressiontestBESTSCREENINGTEST!1.ManteroF,etal.HormoneRes47:284–289,19972.MontwillJ,etal.TheO/NDSTistheprocedureofchoiceforscreeningforCushing’ssyndrome.Steroids1994;59:2296SubclinicalCushing’sSyndrome19DexamethasoneSuppressionTest1mgdexamethasoneat11PMMeasurecortisolat8AMthenextmorningNormal:cortisol<1.8μg/dL(5ug/dl)SpecificityofDSTis7282%(100%)Sensitivity75100%(58%)SeverebipolardepressionandseverealcoholismcangivefalsepositiveresultsIftheDST8AMserumcortisolisabnormal,thenbaselineACTH,serumand24hoururinarycortisolshouldbeobtainedandmidnightsalivarycortisol,ora2daylowdosedexamethasonesuppressiontestisneededtoconfirmautonomyDexamethasoneSuppressionTest20HyperfunctioningHormonalEvaluationSubclinicalCushing’sSyndromePheochromocytomaPrimaryAldosteronismSexhormonesecretingadrenocorticaltumorsHyperfunctioningHormonalEval21PheochromocytomaRarebutfatalcatecholaminesproducingtumorIncidence:28/millionpeople/yearAccountfor5%ofadrenalincidentalomaRuleof10s:10%extraadrenal,10%bilateral,10%familial,10%malignantAsidefromcatecholamines,itcanalsosecretedopamine,ACTH,PTH,calcitonin,VIPPheochromocytomaRarebutfatal22PheochromocytomaClassictriads:SuddensevereheadacheDiaphoresisPalpitations94%specificity;91%sensitivityinhypertensivepopulationPheochromocytomaClassictriads23Pheochromocytoma1976%ofpheoareundiagnoseduntilafterdeath80%ofpatientwithunsuspectedpheowhounderwentsurgeryoranesthesiawilldieAlthoughradiographiccharacteristicscangivesomeclues:EnhancementwithIVonCTHighsignalintensityonT2weightedMRIProminentvascularityThustheneedforscreeningPheochromocytoma1976%ofpheo24DyslipidemiaProminentvascularityNIHState-of-the-ScienceConferenceStatementFeb4-6,2002.2000;29(1):159-185AbdominalCT(61,054CTscansreviewed):4%withadrenaladenomasAutopsies:87,065cases:6%withadrenaladenomas“Plasmafreemetanephrinesarerecommendedasthetestofchoiceforexcludingorconfirmingthediagnosisofpheochromocytoma.CytologyfromFNAcannotdistinguishbenignadrenalmassvs.SexhormonesecretingadrenocorticaltumorsUrinaryfractionatedmetanephrinesandcatecholaminesPalpitationsIsitmetastatic?SexhormonesecretingAdrenocorticalTumorsImagePhenotypeCTScanMass<4cmcanbemonitoredIfmassgrowsmorethan1cmorbecomeshormonallyactive,thenadrenalectomyisrecommended.PrimaryAldosteronismMayoClinicStudySubclinicalCushing’sSyndromeSensitivitywashighestforfractionatedPLASMAfreemetanephrines(99percent)HyperfunctioningHormonalEvaluationImagingSilent8cmpheoDyslipidemiaImagingSilent8cm25PheochromocytomaAvailableTests:Plasmafractionatedfreemetanephrines24hoururinaryfractionatedmetanephrinesandcatecholaminesPlasmacatecholaminesUrinarytotalmetanephrinesUrinaryvanillylmandelicacidWhichtestisbest?PheochromocytomaAvailableTest26LiteratureSupportsSensitivitywashighestforfractionatedPLASMAfreemetanephrines(99percent)Usingreceiveroperatingcharacteristiccurves,sensitivityvaluesatdifferentupperreferencelimitswerehighestforfractionatedplasmafreemetanephrines.“Fractionatedplasmafreemetanephrineswerethebesttestforexcludingpheochromocytomaandshouldbethediagnostictestoffirstchoice.”JAMA2002LiteratureSupportsSensitivity27LiteratureSupportsPLASMAfreemetanephrinesBESTscreeningtestWhenthetestisnegativepracticallyrulesoutpheoCost$100pertestURINARYmetanephrineslesssensitiveUrinaryVMAisoutdatedPresentedattheFirstInternationalmeetingonAdrenalDisease,2002BrazJMedBiolRes33(10)2000Whenthetestisnegative,noothertestsareneeded.LiteratureSupportsPLASMAfree28NIHStateoftheScienceConferenceStatementFinalStatement7/16/2002“Plasmafreemetanephrinesarerecommendedasthetestofchoiceforexcludingorconfirmingthediagnosisofpheochromocytoma.”Managementoftheclinicallyinapparentadrenalmass(incidentaloma).NIHState-of-the-ScienceConferenceStatementFeb4-6,2002NIHStateoftheScienceConfere29Disagreement!Disagreement!30LiteratureSearch“Thefirstinitialtestofchoiceforlowriskpatientsisthe24hoururinaryfractionatedmetanephrinesandcatecholamines.”Althoughelevatedlevelsoffractionatedplasmametanephrineshavehighsensitivityforpheo(99%),thetesthasalowspecificity(85%)andthusshouldbeusedwhensuspicionishigh.LiteratureSearch“Thefirstin31Whattodo?PlasmafractionatedmetanephrinesSens:97100%,Spec8589%UrinaryfractionatedmetanephrinesandcatecholaminesSens:91%,Spec98%Whattodo?Plasmafractionated32HyperfunctioningHormonalEvaluationSubclinicalCushing’sSyndromePheochromocytomaPrimaryAldosteronismSexhormonesecretingadrenocorticaltumorsHyperfunctioningHormonalEval33PrimaryAldosteronism1%ofadrenalincidentalomacharacterizedby:highbloodpressureRefractorytotreatmenthypokalemiaWeakness,crampssuppressedreninactivitymetabolicalkalosisPrimaryAldosteronism1%ofadr34PrimaryAldosteronismPatientswithprimaryaldosteronismhasincreasedriskforcardiovasculardiseaseThusnecessarytoscreenallpatientswithadrenalincidentalomaforPAScreeningtestis:PACandPAC/PRAratioPAC/PRA>30andPAC>20ng/dL90%specandsensitivityforPAIfscreeningtestispositiveneedtoconfirmwithsalinesuppressiontest,adrenalvenoussamplingandimagingPrimaryAldosteronismPatients35midnightsalivarycortisol,ora2-daylow-dosedexamethasonesuppressiontestmidnightsalivarycortisol,ora2-daylow-dosedexamethasonesuppressiontestmidnightsalivarycortisol,or36腎上腺意外瘤指南課件37HyperfunctioningHormonalEvaluationSubclinicalCushing’sSyndromePheochromocytomaPrimaryAldosteronismSexhormonesecretingadrenocorticaltumorsHyperfunctioningHormonalEval38SexhormonesecretingAdrenocorticalTumorsRareTypicallyoccurinthepresenceofclinicalmanifestations(hirsutismorvirilization)SexhormonesecretingAdrenocor39HirsutismHirsutism40SexhormonesecretingAdrenocorticalTumorsRareTypicallyoccurinthepresenceofclinicalmanifestations(hirsutismorvirilization)RoutinescreeningforexcessandrogensandestrogensisnotwarrantedSexhormonesecretingAdrenocor41HormonalWorkupSummary3hormonaltestsnecessaryforworkupofadrenalincidentaloma:1mgovernightdexamethasonesuppresiontestPlasmaorurinaryfractionatedmetaneprinesPlasmaaldosteroneconcentrationandplasmaaldosteroneconcentration/plasmareninactivityratio(PAC/PRA).HormonalWorkupSummary3hormo42TreatmentAllpatientswithdocumentedpheochromocytomaandprimaryaldosteronismshouldundergosurgeryNoprospective,randomizedtrialsforSubclinicalCushing’sSyndromebutconcensusistoproceedwithsurgeryifthepatientisyoungTreatmentAllpatientswithdoc43ThreeMainQuestionsIstheadrenalmasshormonallyactive?Isthemassbenignormalignant?Doesthepatienthaveahistoryof apreviousmalignantlesion? Isitmetastatic?ThreeMainQuestionsIstheadr44midnightsalivarycortisol,ora2-10%extraadrenal,10%bilateral,10%familial,10%malignantmonitoringImagePhenotypeCTScanIfscreeningtestispositiveneedtoconfirmwithsalinesuppressiontest,adrenalvenoussamplingandimagingBrazJMedBiolRes33(10)2000Veryrare:5casesper1millionpopulationhypokalemiaDexamethasoneSuppressionTest2001,Totowa:HumanaPressInc.monitoringRoutinescreeningforexcessandrogensandestrogensisnotwarrantedPheochromocytomaJCEM2000;85:1440.HyperfunctioningHormonalEvaluationImagingPhenotype(features)Ruleof10s:IncidenceIncreaseswithAgeFrequencyofFindingsNoprospective,randomizedtrialsforSubclinicalCushing’sSyndromebutconcensusistoproceedwithsurgeryifthepatientisyoungPrimaryAdrenalCarcinomaVeryrare:5casesper1millionpopulationSmallsizecorrespondstobetterprognosis5yearsurvivalOverall:16%Localizeddisease(stageIandII):42%Metastases:5.3%midnightsalivarycortisol,or45Imagingcomplexsolidandcystic,calcifiedmassImagingcomplexsolidand46PatientwithKnownMalignancy1040%ofpatientswithknownmalignancyhaveadrenalmetastasesatautopsyMostcommonprimaryBreastLungKidneyMelanomaLymphomaPatientwithKnownMalignancy147AssessmentofMalignantPotentialSizeImagingPhenotype(features)AssessmentofMalignantPotent48SizeProbabilityofmalignancyincreaseswithsizeInastudyinvolving887patientswithadrenalincidentalomas,90%ofpatientswithadrenalcarcinomashastumor>4cm(NationalItalianStudyGroup,1997)adrenalcarcinomas2%(<4cm)，6%（46cm)，25%(>6cm)SizeProbabilityofmalignancy49SizeMayoClinicStudy342PatientswithadrenalincidentalomaretrospectivelyevaluatedTumordiameteraveraged2.5cmMostmalignanttumorsmeasured>5cm Incidentallydiscoveredadrenaltumors:aninstitutionalperspective.HerreraMF;GrantCS;vanHeerdenJA;SheedyPF;IlstrupDM.Surgery1991Dec;110(6):101421SizeMayoClinicStudy50SizeConsensusStatementMass>6cmshouldberemovedMass<4cmcanbemonitoredMassbetween46cm:Criteriaotherthansizeshouldbeusedtodictatesurgeryvs.monitoringManagementoftheclinicallyinapparentadrenalmass(incidentaloma).NIHState-of-the-ScienceConferenceStatementFeb4-6,2002.SizeConsensusStatementManagem51AssessmentofMalignantPotentialSizeImagingPhenotypeAssessmentofMalignantPotent52ImagePhenotypeCTScanHounsfieldunit(HU)semiquantitativemethodformeasuringxrayattenuationWater=0HUAdiposetissue=20to150HUKidney=20to50HUBone=1000HULipidrichmassarebenignHU<10onunenhancedCT=benignadenoma100%ImagePhenotypeCTScanHounsfi53ImagePhenotypeCTScanRetrospectiveanalysisof151patientswithadrenalmassesHU<10oracombinationoftumorsize<4cmandHU<20=excludednonadenomasin100percentofcasesHamrahian,etal.JCEM2005;90:871ImagePhenotypeCTScanRetrosp54ImagePhenotypeCTScanContrastwashoutOncontrastenhancedCT,adenomasexhibitrapidwashoutcomparedtononadenomas(metastases,angiosarcoma,pheo,carcinoma…)Washoutof>60%at10min=nocancerWashout<60%at10min=highriskformalignantlesionImagePhenotypeCTScanContras55ImagingmetastasesImagingmetastases56MRIEquallyeffectiveasCTAdenomasareisointensewiththeliveronT2weightedimagesCarcinomasarehyperintensecomparedtotheliveronT2weightedimagesMRIEquallyeffectiveasCT57AtherosclerosisSuddensevereheadacheDisagreement!LiteratureSearchAldosteronoma1%Prominentvascularity（優(yōu)選）腎上腺意外瘤指南IncidenceIncreaseswithAgeSexhormonesecretingadrenocorticaltumorsEquallyeffectiveasCTmidnightsalivarycortisol,ora2-JCEM2000;85:1440.UrinarytotalmetanephrinesHamrahian,etal.ThustheneedforscreeningSilent8cmpheoSubclinicalCushing’sSyndromeRuleof10s:MostfrequenthormonalabnormalityinadrenalincidentalomasSubclinicalCushingsyndrome(SCS),5%PheochromocytomaFNACytologyfromFNAcannotdistinguishbenignadrenalmassvs.malignantItcandistinguishadrenaltissuefrommetastasesFNAisusefulonlyindistinguishingadrenaltumorfrommetastasisandinfectionNeedtoruleoutpheochromocytomabeforeFNAAtherosclerosisFNACytologyfro58MostfrequenthormonalabnormalityinadrenalincidentalomasCost$100pertestAdiposetissue=20to150HURetrospectiveanalysisof151patientswithadrenalmassesIncidence:28/millionpeople/yearCytologyfromFNAcannotdistinguishbenignadrenalmassvs.URINARYmetanephrineslesssensitive85(2):637.PAC/PRA>30andPAC>20ng/dL“Fractionatedplasmafreemetanephrineswerethebesttestforexcludingpheochromocytomaandshouldbethediagnostictestoffirstchoice.ImagePhenotypeCTScan3hormonaltestsnecessaryforworkupofadrenalincidentaloma:ImagingmetastasesRuleof10s:HyperfunctioningHormonalEvaluationNoprospective,randomizedtrialsforSubclinicalCushing’sSyndromebutconcensusistoproceedwithsurgeryifthepatientisyoungNIHStateoftheScienceConferenceStatementDexamethasoneSuppressionTestVeryrare:5casesper1millionpopulationFollowUpWillthemassbecomehypersecretory?Willthemassbecomemalignant?Mostfrequenthormonalabnorma59腎上腺意外瘤指南腎上腺意外瘤指南60（優(yōu)選）腎上腺意外瘤指南（優(yōu)選）腎上腺意外瘤指南61Definition“Masslesiongreaterthan1cmindiameterdiscovered“accidentally”duringaradiographicexaminationperformedforindicationsotherthananevaluationforadrenaldisease.”Managementoftheclinicallyinapparentadrenalmass(incidentaloma).NIHState-of-the-ScienceConferenceStatementFeb4-6,2002.Definition“Masslesiongreater62PrevalenceAutopsies:87,065cases:6%withadrenaladenomasAbdominalCT(61,054CTscansreviewed):4%withadrenaladenomasNowapproachesthe8.7%incidencereportedinautopsyseries

PrevalenceAutopsies:87,065ca63IncidenceIncreaseswithAgeEndocrineandMetabolismClinicsofNorthAmerica.2000;29(1):159-185IncidenceIncreaseswithAgeEn64ThreeMainQuestionsIstheadrenalmasshormonallyactive?Isthemassbenignormalignant?Doesthepatienthaveahistoryof apreviousmalignantlesion? Isitmetastatic?ThreeMainQuestionsIstheadr65AnatomyAnatomy66AnatomyAnatomy67AnatomyPrimaryAldosteronismCushing’sSyndromeDHEA-sPheochromocytomaAnatomyPrimaryAldosteronismCu68FrequencyofFindingsMulticenterstudyof1096casesNonfunctioningadenoma:85%SubclinicalCushing’ssyndrome:9%Pheochromocytoma:4%Aldosteronomas:2%Manteroetal.85(2):637.(2000)

FrequencyofFindingsMulticent69Pheochromocytoma5%AsummaryoftheliteratureWhenthetestisnegative,noothertestsareneeded.IncidenceIncreaseswithAgeSexhormonesecretingadrenocorticaltumorsIncidenceIncreaseswithAgeTypicallyoccurinthepresenceofclinicalmanifestations(hirsutismorvirilization)Veryrare:5casesper1millionpopulationAbdominalCT(61,054CTscansreviewed):4%withadrenaladenomas1976%ofpheoareundiagnoseduntilafterdeathSurgery1991Dec;110(6):101421MostcommonprimaryEquallyeffectiveasCTImagingPhenotype(features)Plasmaaldosteroneconcentrationandplasmaaldosteroneconcentration/plasmareninactivityratio(PAC/PRA).ImagePhenotypeCTScanFrequencyofFindingsAllolio,B.,AdrenalIncidentalomas.AdrenalDisorders,ed.C.G.MargiorisAN.2001,Totowa:HumanaPressInc.Pheochromocytoma5%Frequency70AsummaryoftheliteratureNonfunctioningadenomaApproximately80% SubclinicalCushingsyndrome(SCS),5%Pheochromocytoma5% Aldosteronoma1%adrenocorticalcarcinoma(ACC)<5%Metastaticlesion2.5%Ganglioneuromas,myelolipomas,orbenigncysts AsummaryoftheliteratureNon71考慮是否手術(shù)治療之前準確的功能診斷非常必要嗜鉻細胞瘤要進行認真的術(shù)前準備以避免術(shù)中和術(shù)后的發(fā)作和死亡。原發(fā)性醛固酮增多癥的患者需要明確是否存在腎上腺皮質(zhì)增生及無功能的腎上腺腺瘤。腎上腺源性Cushing綜合征的患者在行切除術(shù)后可能發(fā)生腎上腺皮質(zhì)功能不全，激素的替代以及增減治療需要非常仔細。亞臨床Cushing綜合征的患者是否需要手術(shù)治療仍存在爭議。腎上腺皮質(zhì)癌的患者手術(shù)前需要外科醫(yī)師和內(nèi)分泌科醫(yī)師或腫瘤科醫(yī)師共同協(xié)商決定切除的方式，因為首次切除的效果是生存率的主要預(yù)測因素。超過4cm的腎上腺無功能瘤可以考慮切除。小的髓脂肪瘤或良性的囊腫一般影像學(xué)檢查即可確診，通常不需要治療，除非有癥狀可以考慮手術(shù)治療?？紤]是否手術(shù)治療之前準確的功能診斷非常必要嗜鉻細胞瘤要進行72Algorithmfortheevaluationandmanagementofanadrenalincidentaloma*Reimagein3to6monthsandannuallyfor1to2years;repeatfunctionalstudiesannually for5years.Ifmassgrowsmorethan1cmorbecomeshormonallyactive,thenadrenalectomyisrecommended.Algorithmfortheevaluationa73HyperfunctioningHormonalEvaluationSubclinicalCushing’sSyndromePheochromocytomaPrimaryAldosteronismSexhormonesecretingadrenocorticaltumorsHyperfunctioningHormonalEval74SubclinicalCushing’sSyndromeHypercortisolismwithoutclinicalmanifestationsofCushing’ssyndromeMostfrequenthormonalabnormalityinadrenalincidentalomasSubclinicalCushing’sSyndrome75SubclinicalCushing’sSyndrome2000;29(1):159-185monitoringPurplestriaeProbabilityofmalignancyincreaseswithsizeWhattodo?SexhormonesecretingadrenocorticaltumorsLiteratureSupportsSubclinicalCushing’ssyndrome:9%AdrenalDisorders,ed.IncidenceIncreaseswithAgeMayoClinicStudyPheochromocytomaMass<4cmcanbemonitoredPatientwithKnownMalignancyHyperfunctioningHormonalEvaluation1040%ofpatientswithknownmalignancyhaveadrenalmetastasesatautopsyMayoClinicStudyOsteoporosis?SubclinicalCushing’sSyndromeCentralobesityFacialroundingBuffalohumpEasybruisingPurplestriaeProximalmuscleweaknessEmotional/cognitivechangesSubclinicalCushing’sSyndrome76SubclinicalCushing’sSyndromeIncreaseriskfor:HypertensionDyslipidemiaImpairedglucosetoleranceType2DMAtherosclerosisOsteoporosis?TauchmanovaL,et.al.PatientswithsubclinicalCushing’ssyndromeduetoadrenaladenomahaveincreasecardiovascularrisk.JCEM2000;85:1440.SubclinicalCushing’sSyndrome77SubclinicalCushing’sSyndromeBiochemicalabnormalitiesElevatedurinefreecortisolLoworsuppressedACTHBlunteddiurnalvariationNocortisolsuppressionafter1mgovernightdexamethasonesuppressiontestBESTSCREENINGTEST!1.ManteroF,etal.HormoneRes47:284–289,19972.MontwillJ,etal.TheO/NDSTistheprocedureofchoiceforscreeningforCushing’ssyndrome.Steroids1994;59:2296SubclinicalCushing’sSyndrome78DexamethasoneSuppressionTest1mgdexamethasoneat11PMMeasurecortisolat8AMthenextmorningNormal:cortisol<1.8μg/dL(5ug/dl)SpecificityofDSTis7282%(100%)Sensitivity75100%(58%)SeverebipolardepressionandseverealcoholismcangivefalsepositiveresultsIftheDST8AMserumcortisolisabnormal,thenbaselineACTH,serumand24hoururinarycortisolshouldbeobtainedandmidnightsalivarycortisol,ora2daylowdosedexamethasonesuppressiontestisneededtoconfirmautonomyDexamethasoneSuppressionTest79HyperfunctioningHormonalEvaluationSubclinicalCushing’sSyndromePheochromocytomaPrimaryAldosteronismSexhormonesecretingadrenocorticaltumorsHyperfunctioningHormonalEval80PheochromocytomaRarebutfatalcatecholaminesproducingtumorIncidence:28/millionpeople/yearAccountfor5%ofadrenalincidentalomaRuleof10s:10%extraadrenal,10%bilateral,10%familial,10%malignantAsidefromcatecholamines,itcanalsosecretedopamine,ACTH,PTH,calcitonin,VIPPheochromocytomaRarebutfatal81PheochromocytomaClassictriads:SuddensevereheadacheDiaphoresisPalpitations94%specificity;91%sensitivityinhypertensivepopulationPheochromocytomaClassictriads82Pheochromocytoma1976%ofpheoareundiagnoseduntilafterdeath80%ofpatientwithunsuspectedpheowhounderwentsurgeryoranesthesiawilldieAlthoughradiographiccharacteristicscangivesomeclues:EnhancementwithIVonCTHighsignalintensityonT2weightedMRIProminentvascularityThustheneedforscreeningPheochromocytoma1976%ofpheo83DyslipidemiaProminentvascularityNIHState-of-the-ScienceConferenceStatementFeb4-6,2002.2000;29(1):159-185AbdominalCT(61,054CTscansreviewed):4%withadrenaladenomasAutopsies:87,065cases:6%withadrenaladenomas“Plasmafreemetanephrinesarerecommendedasthetestofchoiceforexcludingorconfirmingthediagnosisofpheochromocytoma.CytologyfromFNAcannotdistinguishbenignadrenalmassvs.SexhormonesecretingadrenocorticaltumorsUrinaryfractionatedmetanephrinesandcatecholaminesPalpitationsIsitmetastatic?SexhormonesecretingAdrenocorticalTumorsImagePhenotypeCTScanMass<4cmcanbemonitoredIfmassgrowsmorethan1cmorbecomeshormonallyactive,thenadrenalectomyisrecommended.PrimaryAldosteronismMayoClinicStudySubclinicalCushing’sSyndromeSensitivitywashighestforfractionatedPLASMAfreemetanephrines(99percent)HyperfunctioningHormonalEvaluationImagingSilent8cmpheoDyslipidemiaImagingSilent8cm84PheochromocytomaAvailableTests:Plasmafractionatedfreemetanephrines24hoururinaryfractionatedmetanephrinesandcatecholaminesPlasmacatecholaminesUrinarytotalmetanephrinesUrinaryvanillylmandelicacidWhichtestisbest?PheochromocytomaAvailableTest85LiteratureSupportsSensitivitywashighestforfractionatedPLASMAfreemetanephrines(99percent)Usingreceiveroperatingcharacteristiccurves,sensitivityvaluesatdifferentupperreferencelimitswerehighestforfractionatedplasmafreemetanephrines.“Fractionatedplasmafreemetanephrineswerethebesttestforexcludingpheochromocytomaandshouldbethediagnostictestoffirstchoice.”JAMA2002LiteratureSupportsSensitivity86LiteratureSupportsPLASMAfreemetanephrinesBESTscreeningtestWhenthetestisnegativepracticallyrulesoutpheoCost$100pertestURINARYmetanephrineslesssensitiveUrinaryVMAisoutdatedPresentedattheFirstInternationalmeetingonAdrenalDisease,2002BrazJMedBiolRes33(10)2000Whenthetestisnegative,noothertestsareneeded.LiteratureSupportsPLASMAfree87NIHStateoftheScienceConferenceStatementFinalStatement7/16/2002“Plasmafreemetanephrinesarerecommendedasthetestofchoiceforexcludingorconfirmingthediagnosisofpheochromocytoma.”Managementoftheclinicallyinapparentadrenalmass(incidentaloma).NIHState-of-the-ScienceConferenceStatementFeb4-6,2002NIHStateoftheScienceConfere88Disagreement!Disagreement!89LiteratureSearch“Thefirstinitialtestofchoiceforlowriskpatientsisthe24hoururinaryfractionatedmetanephrinesandcatecholamines.”Althoughelevatedlevelsoffractionatedplasmametanephrineshavehighsensitivityforpheo(99%),thetesthasalowspecificity(85%)andthusshouldbeusedwhensuspicionishigh.LiteratureSearch“Thefirstin90Whattodo?PlasmafractionatedmetanephrinesSens:97100%,Spec8589%UrinaryfractionatedmetanephrinesandcatecholaminesSens:91%,Spec98%