垂體瘤處理課件

PituitaryAdenomas(Macroadenomas)浙醫(yī)二院內(nèi)分泌科任躍忠20101211PituitaryMacroadenomas

Thesellar蝶鞍regionisasiteofvarioustypesoftumors.Pituitaryadenomasarethemostcommonandaccountfor10-15%ofallintracranialtumors.Tumorsexceeding10mmaredefinedasmacroadenomas,andthosesmallerthan10mmaretermedmicroadenomas.Mostpituitaryadenomasaremicroadenomas.

PathophysiologyPituitarymacroadenomasarebenignepithelialneoplasmscomposedofadenohypophysialcells.Primarymalignanttumorsofthepituitaryareextremelyrare..Pituitarytumordevelopmentisamonoclonalprocesswithseveralcontributingfactors.…arisefromamutatedpituitarycell.…remainunknown.Somepituitarytumorsmayoccuraspartofaclinicalsyndrome.In

multipleendocrineneoplasiatype1(MEN1).RaceNoracialpredilectionexistsforpituitarymacroadenomas.SexAutopsyseriesshowanequaldistributionofpituitarytumorsbetweenmenandwomen.Corticotropinomas..mainlyinwomen,..4:1...Amenorrhea(ormenstrualirregularities),whichisarelativelycommonsymptominwomenwithmacroadenomas,raisesthesuspicionofapituitarylesion.AgeTumorsaffectindividualsofallages,butincidenceincreaseswithage,peakingbetweenthethirdandsixthdecadesoflife.Clinical

HistoryPatientswithpituitarymacroadenomasmaybeasymptomaticormaypresentwithcomplaintsduetohormonalimbalanceormasseffects.

Pituitaryhormone

effectsdependonthehormonesinvolved.Panhypopituitarism…spared.Thelargerthetumor,themorelikelyitistoinvolvemosthormones...Themostsensitivearethesomatotrophsandthegonadotrophs,whereascorticotrophsandthyrotrophstendtobemoreresistant.Hyperprolactinemia

presentswithhypogonadism,infertility不育,amenorrhea,andgalactorrhea乳溢.Hyperprolactinemiacanbeduetoincreasedhormoneproductionbyaprolactinoma,oritcanbetheresultofstalkcompressionbythemacroadenomaregardlessofhormoneactivity..CorticotropinexcesspresentswithCushingdisease.Corticotropinomasarerarelymacroadenomas.Corticotropinsuppressionduetocompressionofthenormalcorticotrophspresentswithglucocorticoidinsufficiency.Theclinicalpictureofsecondaryglucocorticoiddeficiencyismuchmilderthan..Thyrotropinexcesspresentswithsecondaryhyperthyroidism.Thyrotropinomasareveryraretumors.Theypresentmostfrequentlyasmacroadenomas...naturallyaggressive….presentswithsecondaryhypothyroidism.Excessgrowthhormonepresentswithacromegalyastheresultofasomatotropinoma(oftenamacroadenoma),whileinadequategrowthhormonepresentswithfailuretothriveinchildrenbutoftennocomplaintsinadults.Gonadotropinomasmostoftenareasymptomaticandusuallysecreteinactivefollicle-stimulatinghormone(FSH)andluteinizinghormone(LH)-likeglycoproteinsand/oralphasubunit.Theyoftenaremacroadenomasandusuallyresultinhypopituitarism.Rarely,theycanleadtotesticularenlargementinmenandovarianhyperstimulationinwomen.Masseffectsofthemacroadenomamaypresentwithvisualdeficits,headache,elevatedintracranialpressure,orintracranialhemorrhage.PhysicalMostpatientsdonothavephysicalfindingsassociatedwithmacroadenomas.Physicalfindingsmaybeattributabletothemasseffectsorhormonaldisruption.Whenthetumorextendsontotheopticchiasm視交叉,visualfielddeficitsmaybedemonstrable.Suddenincreaseintumorsize,suchascanoccurwithhemorrhage,mayleadtoelevatedintracranialpressure.Hormonallyactivetumorsmightpresentwithsymptomsduetotargetorganstimulation,suchashyperthyroidism,Cushingsyndrome,orhyperprolactinemia.CausesThecauseofpituitarymacroadenomasisunknown.Themostfavoredtheoryattributesmonoclonalneoplastictransformationofpituitarycellsasthecauseoftumorinitiationandgrowth..Workup---LaboratoryStudies

Laboratorytestsincludebasalhormonelevelsanddynamichormonemeasurementsdependingonthetumorstudied.Alltumorsshouldhavescreeningbasal

hormonemeasurements,whichmayincludeprolactin,thyrotropin,thyroxine,adrenocorticotropin,cortisol,LH,FSH,estradiol,testosterone,growthhormone,insulinlikegrowthfactor-1(IGF-1),andalphasubunitglycoprotein.

Dynamichormonetestsareperformedtoassessthefunctionalityofatumorandassistindifferentialdiagnosis.Theyalsocanbeusedtoassessanteriorpituitaryreserve.Thyrotropin-releasinghormone(TRH)causeselevationofserumprolactinandthyrotropin.Prolactinomas,hyperprolactinemicstates,hyperthyroidism,andpanhypopituitarismexhibitabluntedresponse.

Insulin-inducedhypoglycemia

causesariseincorticotropin,cortisol,andgrowthhormone.AbluntedresponseisobservedinCushingsyndrome,growthhormonedeficiency,hypothyroidism,andhyperthyroidism.

Metyrapone美替拉酮causesariseinmorningserum11-deoxycortisolandurinary17-hydrocorticosteroids(17-OHsteroids).AnexaggeratedresponseoccursinCushingdisease,butnoresponseisobservedinothercausesofCushingsyndrome.

Dexamethasonesuppressiontesting

isusedinCushingsyndromeevaluation.Anovernight1-mgdexamethasonedosefailstosuppressmorningserumcortisolinCushingsyndromebutisonlyascreeningtest.Low-doseandhigh-dose….Cosyntropinα1-24促腎上腺皮質(zhì)激素testingandcorticotropininfusiontesting

assistinassessingthehypothalamic-pituitary-adrenalaxisforadrenocorticalinsufficiency.

GnRHcausesanincreaseinLHandFSHlevels.Thisresponseisbluntedinpituitaryhypogonadismbutexaggeratedinprimaryhypogonadism.Testresults,however,arenotverydependable.Workup---ImagingStudies

Pituitaryimaging…Plainskull

radiographsarepooratdelineatingsofttissues.CTscanningisbetteratdepictingbonystructuresandcalcificationswithinsofttissuesthaneitherplain

radiographyorMRI...suchasgerminomas生殖細胞瘤,,craniopharyngiomas,andmeningiomas腦(脊)膜瘤,arebetterdeterminedwithCTscanning…MRIismoreexpensivethanCTscansbutisthepreferredimagingstudyforthepituitarybecauseitprovidesbettervisualizationofsofttissuesandvascularstructures.Noexposuretoionizingradiationoccurs…,T1-weightedimages,fatproduceshigh–signalintensityimages....T2-weightedimagesofstructureswithhighwatercontent,suchascerebrospinalfluidandcysticlesions,producehigh-intensitysignals,whilestructureswithhighfatcontentpresentwithlow-intensitysignals.OtherTestsVisualfieldtestingshouldbeperformed,especiallyintumorsinvolvingtheopticchiasm.Theseverityofvisualdefectsmaydictateamoreaggressivetreatmentcourse.HistologicFindingsThehistologyofpituitarymacroadenomasshowsvaryinglevelsofneoplasticactivity.Frozensectionsareusuallynotdependablefordefinitivediagnosis.Hormonalimmunohistochemicalstainsforneuroendocrinemarkersareuseful,especiallyinthenonfunctioningtumors.Treatment…MedicalCare

Thegoaloftreatmentiscompletecure.Whenthisisnotattainable,reducingtumormass,restoringhormonefunction,andrestoringnormalvisionareattemptedusingmedications,surgery,andradiation.Pituitarymacroadenomasoftenrequiresurgicalinterventionforcure.Theexceptionstothisrulearethemacroprolactinomas,...Prolactin-secretingmacroadenomas

respondtodopaminergicagonists.Themostfrequentlyemployedmedicationsincludebromocriptine,cabergoline卡麥角林.Quinagolide喹高利特isanalternativewithfeweradverseeffectsthanbromocriptine.….(Forprolactin-secretingmicroadenomas,surgicalremovalisfollowedbyrecurrenceinabout50%ofpatients.Therefore,medicaltherapyispreferred.)Growthhormone-secretingtumors

shouldbetreatedsurgically,oftenfollowedbyradiationtherapy....Radiationtherapyresultsin50%reductioningrowthhormonelevelswithin2years,followedbyanadditional25%inthefollowing2years....Medicaltreatmentisusedaftersurgerytosuppressgrowthhormonesecretion,awaitingtheoccurrenceoftheeffectsofradiotherapy.Octreotide善得定isthetreatmentofchoice......Growthhormonereceptorantagonistshavebeenanotheradditiontothetreatmentofacromegaly.DopamineagonistsalsomaybeusedbutarenotaseffectiveasoctreotideCorticotropin-secretingpituitarytumors

aretreatedusingsurgeryandradiationtherapy(however,theyareratherradioresistant).Medicaltherapyisreservedforpatientswhosetherapyfails,......Centrallyactingmedications..includebromocriptine,valproicacid丙戊酸,andcyproheptadine丙戊酸.Peripherallyactingagentsincludeketoconazole,mitotane米托坦,andmetyrapone美替拉酮..Treatment

…SurgicalCare

Pituitarymacroadenomasoftenrequiresurgicalextirpationforcure.Transsphenoidal經(jīng)蝶骨的surgeryistheapproachofchoice.Onlyabout1%…atranscranialapproach.Comparedwithremissionratesof90%inmicroadenomas,macroadenomas..15-37%whentreatedwithsurgeryalone.Radiationtherapyandmedicaltreatmentoftencomplementsurgery.

….ConsultationsWhenapituitarymacroadenomaisdiagnosed,consultationswithanendocrinologist,neurosurgeon,neuroradiologist,andneurophthalmologist神經(jīng)眼科學

should

beconsidered.

以GH瘤為例中國肢端肥大癥診治規(guī)范：治療目標是隨機血清GH≤2.5ug/L；口服葡萄糖負荷血清GH水平≤1.0ug/L；血清IGF水平下降；腫瘤消除或縮??；臨床癥狀消除或減輕；盡可能保留內(nèi)分泌功能或進行激素替代。SSA治療適應(yīng)癥：術(shù)前，縮小腫瘤體積；腫瘤切除后殘余腫瘤的輔助治療；放射治療后的過渡治療；并發(fā)癥治療。2.治療后：定期評估，長期隨診(推薦1年1次）糾正電解質(zhì)紊亂垂體激素替代注意垂體周圍組織損傷下丘腦綜合征尿崩癥SIADH腦耗鹽綜合征3.并發(fā)癥管理：血糖、血壓、骨代謝、心功能、腎功能(專家小組包括：內(nèi)分泌專家、神經(jīng)外科專家、放射治療專家、放射診斷學專家、病理學專家。)MedicationMedicationsareusedtocontrolexcesshormonesecretionortoreplacedeficienthormones.DopaminergicagentsTheseagentsdirectlystimulatepostsynaptic突觸后的dopaminereceptors.Thedopaminergicneuronsinthetuberoinfundibular結(jié)節(jié)漏斗部的processmodulatethesecretionofhormonesfromtheanteriorpituitarybysecretinganinhibitoryfactor,believedtobedopamine.

Bromocriptine(Parlodel)Dopamineagonistusedtonormalizeserumprolactinlevels.Semisynthetic,ergotalkaloidderivative.StrongdopamineD2-receptoragonist.PartialdopamineD1-receptoragonist.Cabergoline(Dostinex)卡麥角林Dopamineagonistusedtonormalizeserumprolactinlevels.Long-actingdopaminereceptoragonistwithhighaffinityforD2receptors.0.25-1mgPOtwiceqwkGrowthhormonereceptorantagonistsUsedforthetreatmentofacromegaly.

Pegvisomant(Somavert)培維索孟Geneticallyengineeredgrowthhormonereceptorantagonistusedtotreatacromegaly.Usefulinpatientsnotrespondingtosomatostatinanalogues.Maybeusedconcurrentlywithsomatostatinanaloguesaftersurgeryandradiation.Somatostatinanalogues生長抑素類似劑Usedtocontrolsymptomsresultingfromexcesshormonesecretion.

Octreotide(Sandostatin)Somatostatinanalogueusedtonormalizegrowthhormonelevels.ActsprimarilyonsomatostatinreceptorsubtypesIIandV.Inhibitsgrowthhormonesecretionandhasmultipleotherendocrineandnonendocrineeffects,includinginhibitionofglucagon,VIP,andGIpeptides.Inpatient&OutpatientMedicationsMedicationsarebasedonhormonalabnormalities.Forinstance,dopaminergicagentsareusedforhyperprolactinemia,andsomatostatinanaloguesareusedforacromegaly.ComplicationsComplicationsresultfrommasseffectsandabnormalhormonefunction.

Pituitaryapoplexy垂體卒中,whichisanacutehemorrhagicinfarctionofapituitarytumor,requiresemergencydecompression.Itpresentswithadrenalcrisisandasevereheadachefollowedbycomaanddeathwithinhoursifnotappropriatelymanaged.Postoperatively,pituitaryhormoneinsufficiency,includingdiabetesinsipidus,hypothyroidism,andhypogonadism,mayoccur.Radiationtreatmentexceeding60Gycanbeassociatedwithopticnerveneuropathyandbrainnecrosis.Othercomplicationsincludevisualimpairment,obesity,and