cushing綜合征（庫欣綜合征）

1/1cushing綜合征（庫欣綜合征）cushing綜合征（庫欣綜合征）庫欣綜合征（庫欣綜合征）【定義】庫欣綜合征的又稱皮質(zhì)醇增多癥（皮質(zhì)醇增多癥）各種原因引起的腎上腺分泌糖皮質(zhì)激素（以皮質(zhì)醇為主）過多導(dǎo)致的臨床綜合征，伴腎上腺雄性激素以及鹽皮質(zhì)激素不同程度分泌增多庫欣綜合征臨床類型：

1。

典型病例2。

重型3。

早期病例4。

以并發(fā)癥為主者5。

周期性【典型病例】1）脂質(zhì)代謝紊亂：

向心性肥胖、滿月臉、水牛背、多血質(zhì)、紫紋等。

鎖骨上窩脂肪墊。

頰部及鎖骨上窩脂肪堆積有特征性機制：

過多皮質(zhì)醇促使脂肪動員、分解增多、合成減少；糖異生加強，血糖升高，分泌增多促進脂肪合成和重新分布插件。

2）蛋白質(zhì)代謝紊亂：

皮膚菲薄，皮膚彈性纖維斷裂，可見微血管的紅色--紫紋。

毛細血管脆性增加易有皮下淤血。

肌萎縮及無力骨質(zhì)疏松，病理性骨折。

機制：

過多皮質(zhì)醇致蛋白質(zhì)分解增加，生糖氨基酸增多致糖異生加強，負氮平衡3）糖代謝紊亂：

外周組織糖利用減少肝糖輸出增多糖異生增加糖耐量受損繼發(fā)性（類固醇性）糖尿病4）電解質(zhì)紊亂：

機制：

過多皮質(zhì)醇致潴鈉排鉀，高血壓，低血鉀（去氧皮質(zhì)酮鹽皮質(zhì)樣作用）、水腫及夜尿增加，低血鉀性堿中毒（異位ACTH綜合征和腎上腺皮質(zhì)癌）5）心血管病變導(dǎo)致高血壓的原因：

皮質(zhì)醇鹽皮質(zhì)樣作用容量擴張血管活性物加壓反應(yīng)增強血管舒張受抑制6）全身及神經(jīng)系統(tǒng)肌無力、不同程度的神經(jīng)、情緒反應(yīng)。

可有類偏狂7）對感染抵抗力下降免疫功能抑制抗體形成受阻中性粒細胞吞噬減弱8）血液改變多血質(zhì)：

（紅細胞，白細胞增多）淋巴組織萎縮淋巴細胞和白細胞百分比率減少9）性腺功能障礙機制：

腎上腺雄激素產(chǎn)生過多及皮質(zhì)醇抑制垂體促性腺激素。

女性多囊卵巢綜合征：

月經(jīng)紊亂或閉經(jīng)、痤瘡、多毛、男性化（生須、喉結(jié)增大、乳房萎縮、陰蒂肥大-腎上腺癌？）男性性功能低下：

陰莖縮小，睪丸變軟各種類型的病因及臨床特點1、依賴ACTH的庫欣綜合征（1）依賴垂體ACTH的庫欣?。?0%）庫欣綜合征中最常見好發(fā)年齡為20～40歲女性多于男性（女：

男=2:1）病因：

垂體ACTH微腺瘤（直徑＜10mm）或大腺瘤（直徑＞10mm，蝶鞍受累達10%～15%，可有視野缺損、雙顳側(cè)偏盲）或下丘腦功能失調(diào)（垂體結(jié)構(gòu)功能正常）腫瘤組織病理特點：

（1）可有多種腫瘤類型：

嫌色細胞瘤、嗜堿性細胞瘤、嗜酸性細胞瘤、混合性細胞瘤（2）促腎上腺皮質(zhì)激素增多導(dǎo)致雙側(cè)腎上腺皮質(zhì)束裝帶、網(wǎng)狀帶增生腫瘤組織功能特點：

（1）垂體ACTH瘤為部分自主性，大劑量DXM可抑制其分泌（2）不依賴CRH（3）促腎上腺皮質(zhì)激素瘤可同時分泌多種激素，如：

PRL（2）異位ACTH綜合征（異位ACTH綜合征）垂體外惡性腫瘤分泌ACTH增多，雙側(cè)腎上腺皮質(zhì)增生。

可由小細胞肺癌、支氣管類癌、胸腺癌、胰腺癌等引起（有些還可分泌CRH，ACTH釋放激素）。

占庫欣綜合征10%分型：

1）緩慢發(fā)展型2）迅速進展型常見原因（按發(fā)病率順序）：

小細胞肺癌、支氣管類癌胸腺癌胰腺癌（胰島細胞癌）嗜鉻細胞瘤神經(jīng)母細胞瘤甲狀腺髓樣癌以及腎上腺髓質(zhì)睪丸、卵巢parotidglandGastrointestinaltumor2,CushingindependentsyndromewithoutACTH(1)adrenalcorticaladenomaCushing’ssyndrome,20%AdultmalesaremorecommonThediameterofadenomarangedfrom3to4cmWeight40g+(5~30g)EnvelopeintegrityOneisrare,theotherismanyTheonsetismild,theconditionisnotseriousHirsutismandandrogenlevelsaremildMacroscopicviewoftheadrenalgland:thecapsuleisintact,brownishyellow,smoothandhomogeneous,andclearlydemarcatedfromnormaladrenaltissueMicroscopically,thecellsarearrangedinnestsortrabeculae,richinlipids,cytoplasmclear,andcellssimilartothoseofnormaladrenalzonacell(2)adrenocorticalcarcinomaAccountforCushing‘ssyndrome5%Thevolumeof100g,tumordiameterover5cmCapsuleinvasion,rapidgrowth,latemetastasistolymphnodes,liver,lungTheclinicalsymptomswerehypertension,hypokalemia(DOCincrease),femalehirsutism,acneandandrogenDOC:11-deoxycorticosterone(corticosterone)(3)bilateraladrenalnodularhyperplasiawithoutACTHItisalsocalledMeadorsyndromeorprimarypigmentednodularadrenaldiseaseMostlyforchildrenCushingsyndromeorfamilialonsetAdrenalnodules(mostly0.5cmindiameter)ACTHdecreaseLargedosesofDXMarenotinhibited(autonomoussecretion)(4)bilateraladrenalnodularhyperplasiawithoutACTHAdrenalenlargement,weightupto24~500gNodulediameter0.5cmMostlybenignACTHdecreaseLargedosesofDXMdidnotinhibitsignificantly[diagnosticprocedure]IsitCushing’ssyndrome?TheetiologyofCushing’ssyndromeI.diagnosisofCushing’ssyndromeClinicalmanifestation：

1.havetypicalsymptomsandsigns,accordingtotheappearanceofthediagnosisThemostvaluablesigns:fullmoonface,sanguineandpurplelines2.atypicalsymptoms(withheartfailure,pathologicalfracture,neurologicalsymptomsasthefirstsymptom),payattentiontoidentification[laboratoryandspecialexaminations]1.bloodbiochemistry:Decreasedbloodpotassium,metabolicalkalosis,andimpairedglucosetolerance2.imagingexamination:X-ray:osteoporosis,asmallnumberofsellaenlargementAdrenalBscanorCT:bilateraladrenalhyperplasiaortumorMRI:pituitarynodulesortumors3.glucocorticoidabnormalitiesweremeasured(1)normalplasmacortisolCircadianrhythms(g/dl)8Am:275to550nmol/L(10~20)4Pm:85to275nmol/L(3~10)12N140nmol/L(5)Abnormalcircadianrhythmofplasmacortisol:circadianrhythmdisappeared,plasmacortisollevelselevatedandnighttimehigherthandaytime(2)24hurinefreecortisol(free,cortisol)(24hUFC);Plasmafreecortisol;glomerularfiltration.Reabsorptionoflargerenaltubules.Smallpartisexcretedwithuric,namelyuricfreecortisol.Approximateadrenalcortisolsecretionrateisnotinfluencedbycircadianrhythm.ItisofgreatdiagnosticvalueEctopicACTHsyndromeandadrenalcorticalcarcinomaweresignificantlyincreasedCushing’sdiseaseandadenomaweremildormarkedlyelevatedNormalvalue:130~304nmol/24hUCushing’ssyndromemayberuledouton3consecutiveoccasions(3)dexamethasone(dexamethasone,DXM)suppressiontestObjective:whetherthehypothalamuspituitaryadrenalaxisisinhibitedbyexogenousglucocorticoids?Whydexamethasone?Apowerful(prednisone40times)andasmallamountItsmetaboliteurineexcretionislow,doesnotaffecttheurinemetabolitedeterminationDexamethasoneDringhasbeenmodifiedby16alpha-methyl.Cortisolantibodies(targetingcortisol,Dring)didnotreactwithdexamethasoneanddidnotaffectbloodandurinecortisollevelsA.smalldosedexamethasonesuppressiontestObjective:toidentifyobesityandCushing’sdiseaseMethods:oraladministrationofdexamethasone,0.75mg,andQ8H,for2days.24h,urine,17-OHand24hUFCweremeasuredbeforeandseconddaysbeforeandafterthetestResults:innormalsubjects,24h,17-OH,24handFCinurineweresuppressedtobelow50%ofthecontrolvalue.ThemajorityofCushingsyndromecannotbesuppressedtolessthan50%ofthecontrolvalueB.largedosedexamethasonesuppressiontestObjective:toidentifyectopicACTHsyndrome,AdenomaorcarcinomaofadrenalcortexMethods:oraladministrationofdexamethasone,0.75mg,andQ8H,for2days.24h,17-OHand24hurineFCweremeasuredbeforeandseconddaysbeforeandafterthetestResults:largedosesofDXMcouldcompletelyinhibitACTHsecretioninpatientswithCushing’ssyndrome.MostofthepatientswithectopicACTHsyndromeandadrenalcorticaltumorcannotbeinhibited(4)determinationofurinarymetabolitesA.24hurinary17-OHCS(17-hydroxycorticosteroid)Fourhydrogenmetaboliteofcortisolandcortisone24hurinary17-OHCSdisplacementisabout24h,andcortisolsecretionamountsfrom25%to40%Normal:8.3to33.8mol/24hurineException:55Mumol(20mg)/24hurineCushing:morethan75mol(25mg)/24hurineB.24hurinary17-KS(17-ketosteroid)AndrogensandmetabolitessecretedbythetestesandadrenalglandsMaleurine17-KSof1/3comesfromtestis,and2/3fromadrenalglandWomencomemainlyfromtheadrenalglandsandasmallamountfromtheovariesEctopicACTHsyndromeandadrenalcorticalcarcinomaweresignificantlyincreased4.determinationofplasmaACTHACTHisderivedfromPOMC(pituitarygland)Innormalsubjects,ACTHhasthesamecircadianrhythmascortisolSignificance:Cushing’sdiseaseandectopicACTHsyndromeincreaseACTH,decreasecircadianrhythmanddecreaseCRH,whichisdifferentfromadrenaltumorNormalvalue:8Am2.31~18pmol/L(10.5~82pg/ml)4Pm1.7~16.7pmol/L(7.6~76pg/ml)12Mn0~8.7pmol/L(0~39.7pg/ml)[treatment]One,Cushing,s,diseasetreatment:1.transsphenoidalpituitarytumorsurgeryispreferred,themostidealadrenalfunctionaweektreatmentafteroperationfortreatmentofsurgicalsuccesstemporarilyreduceadrenalinsufficiency:surgery,intravenousinjectionofhydrocortisone300mg;afterfirstdays200mg,secondto3dayseach150mg;fourth~5dayseverysixth~7100mg;eachday50mg.Oneweeklater,prednisonelasted5to10mg/dfor6~12months.ThesecretoryfunctionofACTHrecoveredat4~6monthsafteroperation2.failedtoremovepituitaryadenomaornotsurgery,theadrenalsideofallcut,theothersideofsubtotal(90%)ortotalresection,pituitaryradiotherapy(linearaccelerator).PostoperativeattentionwaspaidtothepreventionandtreatmentofNelsonsyndrome(hyperpigmentationoftheskin,elevatedACTH,andpituitaryadenomas).Hormonereplacementtherapy3.pituitaryradiotherapy:mildorchildren.Theeffectiverateofadultsrangedfrom15%to20%4.pituitaryadenoma:craniotomy5.drugtherapy1)bromocriptine(bromocriptine):DopaminereceptorpotentiatingagentsinhibitACTH,PRL,andGHCushingdiseaseprolactinelevation,canusebromocriptinehiddenfrom5to20mg/d(2)serotonininhibitors,pethidineDirections:24mg/d.Actingonthebrainabovethepituitarygland,thecourse