Cushing综合症.ppt

CushingsyndromeCushing综合症,Definition,Cushingsyndrome,theconstellationofclinicalsignsandsymptomsresultingformchronicglucocorticoidexcess,wasprobablyfirstdescribedin1899,定义,为各种病因造成肾上腺分泌过多的糖皮质激素（主要是皮质醇）所致病症的总称主要临床表现为满月脸，多血质外貌，向心性肥胖、痤疮、皮肤紫纹高血压和骨质疏松等,AetiologyClinicalpresentationlaboratoryexaminationDiagnosisanddifferentialdiagnosisTreatment(principle)Prognosis,病因分类临床表现实验室检查诊断及鉴别诊断治疗(原则)预后,Aetiology病因分类,Hypothalamus下丘脑（CRH）pituitarygland垂体（ACTH）adrenalcortex肾上腺皮质zonaglomerulosazonafasciculatazonareticularis（Aldosterone）（cortisol）（gonadalhormone）,+,+,-,-,Aetiology,ACTH-dependentCushingsyndromeCushingdiseaseEctopicACTHsyndromeACTH-independentCushingsyndromeAdrenocorticaladenomaAdrenocorticaladenocarcinomaMicronodularadrenaldiseaseMassivemacronodularadrenaldisease,病因分类,依赖ACTH的cushing综合症cushing病异位ACTH综合症非依赖ACTH的cushing综合症肾上腺皮质腺瘤肾上腺皮质癌原发性色素结节性肾上腺病大结节性巨大肾上腺病,Clinicalfeature各型临床特征,CushingDisease,ItisthemostcommontypeofCushingsyndrome,andaccountsforabout70%ofthesyndromePathogenesisMostpatientshaveACTH-secretinganteriorpituitarycorticortropemicroadenomas(10mmindiameter),butasmallnumberhavediffusecorticotropehyperplasiaandpituitarymacroadenoma,Cushing病,最常见，约占cushing综合症的70%,多见于成人，女性多于男性，是由于垂体分泌过多的ACTH所致病因垂体微腺瘤80%垂体大腺瘤10：压迫、侵袭等症状下丘脑功能紊乱,EctopicACTHsyndrome,ThemajorityofpatientswithectopicACTHsyndromehaveoutsidepituitarytumorOthersitesarepulmonarycarcinosis,carcinoidofbronchus,thymiccarcinomapancreaticcancer,chromaffintumor,medullarycarcinomaofthyroidandsoon,异位ACTH综合症,继发于垂体以外的恶性肿瘤小细胞肺癌、支气管类癌、胸腺癌、胰腺癌、嗜铬细胞瘤、神经母细胞瘤等等临床上分两型缓慢进展型迅速进展型,Adrenocorticaladenoma,Patientswithadrenaladenomausuallyhavegradualonsetofsignofhypercortisolism,accountsforabout15-20%ofthesyndromeAdenomaisroundorellipse,diameteris3-4cm,weightisabout40g,肾上腺皮质腺瘤,多见于成人，男性多于女性15%-20%腺瘤呈圆形或椭圆形，直径约3-4cm，重40g左右，包膜完整其病缓慢，病情中等，多毛及雄激素增多少见,Adrenocorticaladenocarcinoma,Itoccursinlowerthan5%patientsofcushingsyndromePatientswithadenocarcinomatendtohaveamoreacuteandprogressivecourseandvirilizingeffectsmaypredominateThebulkoftumorislarger,肾上腺皮质腺癌,占cushing综合症的5以下瘤体积大（直径5-6cm)，肿瘤可浸润包膜病情重，进展快，重度cushing综合症的表现(低钾性碱中毒、女性男性化）,Micronodularadrenaldisease,ThediseaseisalsoknownasMeadorssyndromeAbouthalfofpatientswiththisdisorderhavenodistinctiveclinicalpresentationotherthanbeingyoung-alwaysyoungerthan30yearsofage,halfyoungerthan15yearsandsomeinfants,原发性色素结节性肾上腺病,此病又称这为Meador综合症或原发性色素性结节性肾上腺疾病患者多为儿童和青少年临床表现：一部分同一般的临床表现一部分为家族性，呈显性遗传(Carney综合症）,Massivemacronodularadrenaldisease大结节性巨大肾上腺病,Clinicalpresentation临床表现,典型病例重型cushing综合症早期病例以并发症为主者周期性或间歇性,Typicalcases典型病例,Clinicalpresentation1,Progressiveobesityisthemostcommonsign.Itisusuallycentral,involvingtheface,necktrunkandabdomenAlloverthebodyandnervoussystem:weakness,changeofemotionandsoonTheskinisatrophic,thestratumcorneumisthinned,andthereislossofsubcutaneousfatallowingsubcutaneousbloodvesselstobeenseen,Clinicalpresentation2,CardiovascularcomplicationisamajorcauseofmorbidityanddeathinuntreatedCushingsyndromeModeratehypertensioniscommonGlucocorticoidsuppressimmunefunctionInflammatoryandfebrileresponsestobacterialinfectionaresuppressedDysbolismandsexualdisturbancesometimesoccur,临床表现1,满月脸、多血质外貌、向心性肥胖,临床表现2,全身和神经系统症状：肌无力，常有不同程度的精神、情绪变化皮肤表现：皮肤薄，微血管脆性增加，易出现淤斑、紫纹,易合并真菌感染,有时可出现皮肤色素沉着,临床表现2,心血管表现：高血压心衰、脑血管意外凝血功能异常(血小板，纤维蛋白原），脂代谢紊乱，动静脉血栓对感染的抵抗力减弱使达到炎症病灶的单核细胞减少巨噬细胞对抗原的固定、吞噬和杀伤力减弱中性粒细胞运动能力，吞噬作用减弱抗体的形成受到阻抑,临床表现3,性功能障碍：月经减少、不规则、停经、痤疮等明显男性化（警惕肾上腺癌）代谢障碍：脂、蛋白、糖代谢低钾性碱中毒，低钙骨质疏松，伤口愈合不良，生长发育延迟,重型cushing综合症,多由癌肿所致，病情严重，进展迅速体重减轻高血压、浮肿、低钾性碱中毒,早期病例,全身情况较好以高血压为主肥胖、向心性的特点不够显著,以并发症为主者,Cushing综合症本身不明显多以并发症就诊：心衰、脑卒中病理性骨折、精神症状、肺部感染等等,周期性或间歇性,Laboratoryexamination实验室检查,Laboratoryexamination,ThelaboratoryexaminationofCushingsyndromeiscortisolhypersecretion.Increasedurinaryexcretionofcortisolandurinary17-OHLossofrhythmofplasmacortisol,ACTHLossofnormalsuppressibilityofcortisolbylow-dosedexamethasone,实验室检查,皮质醇分泌增多，失去昼夜分泌节律，且不能被小剂量地塞米松抑制试验所抑制尿17羟皮质类固醇、游离皮质醇增高血浆皮质醇浓度增高小剂量地塞米松抑制试验,皮质醇分泌增多，失去昼夜节律，不能被小剂量地塞米松抑制,DiagnosisandDifferentialdiagnosis诊断和鉴别诊断,Diagnosis,TheclinicaldiagnosisofCushingssyndromeisconfirmedbyclinicalpresentation,cortisolhypersecretion,lossofnormalrhythmincortisolandlossofnormalsuppressibilityofcortisolbylow-dosedexamethasone,诊断,临床表现皮质醇分泌增多，失去昼夜分泌节律尿17-羟皮质醇和游离皮质醇增高不能被小剂量地塞米松所抑制,病因诊断,Differentialdiagnosis,CushingssyndromeneedstoidentifywiththefollowingdiseasesSimpleobesityType2diabetesAlcoholismandhepaticlesionDepressivedisorder,鉴别诊断,2型糖尿病：临床表现、皮质醇节律正常单纯性肥胖：地米抑制试验、皮质醇节律正常酗酒兼有肝损害者，出现假性cushing综合症抑郁症：临床表现,Treatment,TreatmentofCushingsyndromeisaimedatfollowinggoals:CureofthesyndromebyreductionofcortisolsecretiontonormalEradicationofanytumorthreateningthehealthofpatientsPreventionofpermanentdependencyonmedicationsAvoidanceofpermanenthormonedeficiency,Treatment-cushingdisease,TranssphenoidalmicroadenomectomyisthemostrationalcurrenttreatmentforCushingdiseaseInpatientswhoarenotcuredbythistreatment,threeoptionsremainReoperateonthepituitaryglandRadiatethepituitaryglandPerformsurgicaladrenalectomyandcorticoidantagonist,cushing病的治疗,经蝶窦切除微腺瘤，是本病的首选方法一侧肾上腺全切，另一侧肾上腺全部或大部分切除，术后可能并发Nelson综合症开颅手术治疗，如不能全部切除，可在术后辅以放疗阻滞肾上腺皮质激素合成的药物,Treatment-Adrenocorticaladenomaandadenocarcinoma,SmalladenomascanberemovedbylaparascopyLargeadenomasandcarcinomasrequireanopenflankortransabdominalapproachThecurewithsurgicalremovalofadrenaladenomaisvirtually100%,肾上腺腺瘤、腺癌的治疗,肾上腺腺瘤手术可获根治，术后采用氢化可的松替代腺癌应尽可能早作手术，如不能，采用药物治疗,Treatment-EctopicACTHsyndrome,Whenpossible,thetumorshouldbesurgicallyexcised,removingthesourceofectopicACTHandtherebycuringthemetabolicdisorderInmostpatients,however,thetumorisnonresectableatthetimeofdiagnosis.Chemotherapyorradiationtherapy,orbothmaybehelpful,异位ACTH综合症的治疗,治疗原发性的恶性肿瘤手术、放疗、化疗使用肾上腺皮质激素合成阻滞药,Adrenalenzymeinhibitors,O,p-DDDAminoglutethimideSU4885Ketoconazole,肾上腺皮质激素合成阻滞药,米托坦氨鲁米能美替拉酮酮康唑,手术前后的处理,患者血浆皮质醇浓度