PheochromocytomaandParaganglioma中南大學湘雅二醫院代謝內分泌研究所盛志峰WHOdefinition(2004)Intra-adrenalparaganglioma

Pheochromocytoma(NE,EP)Extra-adrenalparagangliomasextra-adrenalsympathetic(abdominal,pelvis)orparasympatheticparaganglia(head,neck)(NE,DA)

Zuckerkandlorgan(NE,EP)Significanceofdiagnosis(1)curablehypertension:surgicalremoval(2)Ariskoflethalparoxysmexists,

(3)10%ofthetumorsaremalignant,(4)between10~20%ofthesetumorsarefamilial,andtheirdetectionintheprobandmayresultinearlydiagnosisinotherfamilymembersClinicalPresentation1Hypertension/cardiovasculardisease(paroxysmal/sustained/resistant)labilityinbloodpressureandorthostatichypotensionepisodicreleaseofcatecholamineschronicvolumedepletionimpairedsympatheticreflexes.Inadditiontovolumedepletion,alteredsympatheticvascularregulationmayhavearoleinorthostasis,whichisfrequentlyobservedinpatientswithpheochromocytomaSymptomsoforthostatichypotension(e.g.,lightheadedness,presyncope,syncope)maydominatethepresentation,especiallyinpatientswithepinephrine-ordopamine-predominanttumorshypotenison/shock/

Heartdisease2Metabolicdisturbances(glucose/lipid/electrolytes)Fastinghyperglycemiaanddiabetesmellitusarecausedinpartbytheα-adrenergicinhibitionofinsulinrelease.AlthoughhypercalcemiamaybeasignofMEN2,itisusuallyisolatedandresolveswithresectionofthecatecholamine-secretingtumor.Calcitoninsecretionisinpartacatecholaminedependentprocess;serumcalcitoninconcentrationsarefrequentlymildlyelevatedinpatientswithpheochromocytoma,usuallyunrelatedtoMEN2.3.AdditionalclinicalsignsofpheochromocytomaConstipation/Raynaud’sphenomenon,livedo

reticularis,erythrocytosismasseffectsfromthetumorPainlesshematuriaandparoxysmalattacksinducedbymicturitionanddeficationareassociatedwithurinarybladderparagangliomas.SomeofthecosecretedhormonesACTH(Cushing’ssyndrome),parathyroidhormone-relatedpeptide(hypercalcemia),vasopressin(syndromeofinappropriateantidiuretichormonesecretion),vasoactiveintestinalpeptide(waterydiarrhea)growthhormone–releasinghormone(acromegaly).ClinicalPresentationA“ruleof10”10%extra-adrenal10%occurinchildren10%multipleorbilateral10%recuraftersurgicalremoval10%malignant10%arefamilial(nowadays>20%)10%ofbenignsporadicadrenalpheochromocytomasarefoundasadrenalincidentalomashereditarysyndromeswithpheochromocytomasorparagangliomasCaseDetectionHyperadrenergicspells(e.g.,self-limitedepisodesofpalpitations,diaphoresis,headache,tremor,orpallor)ResistanthypertensionAfamilialsyndromethatpredisposestocatecholaminesecretingtumors(e.g.,MEN2,NF1,VHL)AfamilyhistoryofpheochromocytomaAnincidentallydiscoveredadrenalmassHypertensionanddiabetesPressorresponseduringanesthesia,surgery,orangiographyOnsetofhypertensionatayoungage(<20years)IdiopathicdilatedcardiomyopathyAhistoryofgastrointestinalstromaltumororpulmonarychondromas(Carneytriad)CatecholaminemetabolismSensitivityandspecificityofbiochemicaltestsforthedetectionofpheochromocytomaorparagangliomaBiochemicaltestSensitivitySensitivity(%)Specificity(%)ChildrenAdultsChildrenAdultsPlasmanormetanephrineandmetanephrine100999489Plasmanorepinephrineandepinephrine92849181Urinarynormetanephrineandmetanephrine100979569Urinarynorepinephrineandepinephrine100868388Urinaryvanillylmandelicacid-64-95Bloodsamplingshouldbeperformedatasupinepositionafterabout15–20minsofi.v.catheterinsertion.Food,caffeinatedbeverages,strenuousphysicalactivity,orsmokingarenotpermittedatleastabout8–12hoursbeforethetesting.Theelevationofplasmametanephrinesofmorethan4-foldabovetheupperreferencelimitisassociatedwithcloseto100%probabilityofthetumor.ClonidineSuppressionTestClonidineisacentrallyactingα2-adrenergicreceptoragonistthatnormallysuppressesthereleaseofcatecholaminesfromneuronsbutdoesnotaffectthecatecholaminesecretionfromapheochromocytoma.Clonidine(0.3mg)isadministeredorally,andplasmafractionatedcatecholaminesormetanephrinesaremeasuredbeforeand3hoursafterthedose.Inpatientswithessentialhypertension,plasmacatecholamine/normetanephrineconcentrationsdecrease.However,theseconcentrationsremainincreasedinpatientswithpheochromocytoma.[123I]-labeledmeta-iodobenzylguanidine

scintigraphy([123I]-MIBG)[18F]-FDOPAPET

preoperativepreperationPhenoxybenzamine(Dibenzyline),anα-adrenoceptorblocker,ismostcommonlyusedforpreoperativecontrolofbloodpressure.Thedrugisinitiallyadministeredorallyatadoseof10–20mgtwicedaily.Alternativestophenoxybenzamineforblockadeofcatecholamine-inducedvasoconstrictionincludecalciumchannelblockersandselectivecompetitiveα1-adrenoceptorblockingagents,suchasterazosinanddoxazosinβ