库欣综合征曾正陪.ppt

库欣综合征,曾正陪北京协和医院内分泌科,库欣综合征的发现,肾上腺的结构,球状带,束状带,网状带,髓质,库欣综合征的病因从激素分泌分类,库欣综合征的病因从激素分泌分类,库欣综合征(Cushingsyndrome,皮质醇增多症)Sincecortisolproductionbytheadrenalglandsisnormallyunderthecontrolofthepituitary(likethethyroidgland),overproductioncanbecausedbyatumorinthepituitaryorwithintheadrenalglandsthemselves.因垂体或肾上腺肿瘤分泌过多皮质醇所致的一组症候群库欣病(Cushingdisease)WhenapituitarytumorsecretestoomuchACTH(AdrenalCorticalTropicHormone),itsimplycausestheotherwisenormaladrenalglandstoproducetoomuchcortisol.ThistypeofCushingssyndromeistermedCushingsDisease“.Inthiscase,serumcortisolwillbeelevated,and,serumACTHwillbeelevatedatthesametime.因垂体瘤分泌过多促肾上腺皮质激素(ACTH),刺激肾上腺分泌过多皮质醇所致的库欣综合征,库欣综合征的病因从病变部位分类,垂体瘤（PituitaryAdenomas）PituitaryadenomascausemostcasesofCushingssyndrome.Theyarebenign,ornon-cancerous,tumorsofthepituitaryglandwhichsecreteincreasedamountsofACTH.Mostpatientshaveasingleadenoma.Thisformofthesyndrome,knownasCushingsdisease,affectswomenfivetimesmorefrequentlythanmen.异位ACTH综合征(EctopicACTHSyndrome)Somebenignormalignant(cancerous)tumorsthatariseoutsidethepituitarycanproduceACTH.ThisconditionisknownasectopicACTHsyndrome.Lungtumorscauseover50percentofthesecases.Menareaffected3timesmorefrequentlythanwomen.ThemostcommonformsofACTH-producingtumorsareoatcell,orsmallcelllungcancer,whichaccountsforabout25percentofalllungcancercases,andcarcinoidtumors.OtherlesscommontypesoftumorsthatcanproduceACTHarethymomas,pancreaticisletcelltumors,andmedullarycarcinomasofthethyroid.,库欣综合征的病因从病变部位分类,肾上腺肿瘤(AdrenalTumors)Sometimes,anabnormalityoftheadrenalglands,mostoftenanadrenaltumor,causesCushingssyndrome.Theaverageageofonsetisabout40years.Mostofthesecasesinvolvenon-canceroustumorsofadrenaltissue,calledadrenaladenomas,whichreleaseexcesscortisolintotheblood.Adrenocorticalcarcinomas,oradrenalcancers,aretheleastcommoncauseofCushingssyndrome.Cancercellssecreteexcesslevelsofseveraladrenalcorticalhormones,includingcortisolandadrenalandrogens.Adrenocorticalcarcinomasusuallycauseveryhighhormonelevelsandrapiddevelopmentofsymptoms.,库欣综合征的病因,家族性库欣综合征(FamilialCushingsSyndrome)MostcasesofCushingssyndromearenotinherited.Rarely,however,someindividualshavespecialcausesofCushingssyndromeduetoaninheritedtendencytodeveloptumorsofoneormoreendocrineglands.InPrimaryPigmentedMicronodularAdrenalDisease,childrenoryoungadultsdevelopsmallcortisol-producingtumorsoftheadrenalglands.InMultipleEndocrineNeoplasiaTypeI(MENI),hormonesecretingtumorsoftheparathyroidglands,pancreasandpituitaryoccur.CushingssyndromeinMENImaybeduetopituitary,ectopicoradrenaltumors.,病因比例（%）ACTH依赖性80库欣病68异位ACTH综合症12异位CRH综合症1ACTH非依赖性20肾上腺腺瘤10肾上腺腺癌8双侧肾上腺小结节增生1大结节增生1引自“WilliamsTextbookofEndocrinology,第9版,库欣综合症病因分类和相对比例,CausesofAdrenalCushingsSyndrome,库欣综合征的发病率,itisrelativelyrareandmostcommonlyaffectsadultsaged20to50.Anestimated10to15ofeverymillionpeopleareaffectedeachyear.库欣病发病率在美国每百万人口每年发病约5-25例。我国尚无确切的流行病资料。男女性别之比为1:3-8，男女差别极为显著，原因尚不明。库欣病可发生在任何年龄，以25-45岁为多见。,库欣综合征的临床表现,库欣综合征的临床表现,症状或体征出现频率(%)向心性肥胖79-97多血质50-94糖耐量受损39-90无力及近端肌病29-90高血压74-87心理改变31-86瘀斑23-84女子多毛64-81月经稀发或闭经55-80,库欣综合征的临床表现,症状或体征出现频率(%)阳痿55-80痤疮、皮肤多油26-80紫纹51-71水肿28-60背痛、病理性骨折40-50多饮、多尿25-44肾结石15-19色素沉着4-16头痛0-47突眼0-33,库欣综合征的诊断,定性诊断确定是否为库欣综合征？临床表现-症状、体征实验室检查血浆皮质醇水平测定皮质醇昼夜节律消失单次血皮质醇测定诊断价值不大24小时尿游离皮质醇(24hUFC)浓度测定可避免血皮质醇的瞬时变化避免血中皮质醇结合球蛋白（CBG)的影响诊断符合率98%,库欣综合征的诊断,定性诊断确定是否为库欣综合征？小剂量地塞米松抑制试验地塞米松0.5mgg6hx2天留24小时尿-对照日及服药第二天服药第二天24hUFC90%胰岛素低血糖试验正常人血ACTH及F增高库欣综合征低血糖应激不能引起血ACTH及F水平显著上升,库欣综合征的诊断,定位诊断明确库欣综合征的病因大剂量地塞米松抑制试验地塞米松2mgg6hx2天留24小时尿-对照日及服药第二天库欣病-服药第二天24hUFC被抑制到对照日50%以下诊断符合率80%肾上腺腺瘤或腺癌-不能被抑制到50%以下异位ACTH综合征大多不被抑制,库欣综合征的诊断,定位诊断明确库欣综合征的病因血ACTH水平测定肾上腺皮质肿瘤血ACTH水平低于正常低限库欣病、异位ACTH综合征血ACTH水平不同程度升高异位ACTH综合征显性肿瘤ACTH明显高于库欣病隐性肿瘤ACTH与库欣病重叠血ACTH测定对鉴别ACTH依赖性和非依赖性有肯定的意义对鉴别垂体性或异位ACTH分泌仅作参考,库欣综合征的诊断,定位诊断明确库欣综合征的病因甲吡酮试验鉴别垂体性或肾上腺性750mgg4hx1天，24小时后库欣病人血N-POMC显著升高异位ACTH综合征变化不明显CRH兴奋试验鉴别库欣病或异位ACTH综合征静注羊CRH1-41100g或1g/kg体重库欣病-血ACTH、F水平显著上升异位ACTH综合征无反应静脉插管分段取血测定ACTH浓度-鉴别库欣病或异位ACTH综合征对垂体ACTH瘤及异位ACTH综合征进行定位,CRH,HYPOTHALAMUS,PITUITARYADENOMA,ADRENAL,GLANDS,CUSHINGDISEASE,ACTH,PLASMACORTISOL,NEGATIVE,FEEDBACK,WilliamE.Winter,MD,NEGATIVE,FEEDBACK,CRH:suppressed,HYPOTHALAMUS,PITUITARY,ADRENAL,GLANDS,EctopicACTH,ACTH,PLASMACORTISOL,NEGATIVE,FEEDBACK,WilliamE.Winter,MD,Pit.ACTH:suppressed*,*overall:ACTHiselevated,NEGATIVE,FEEDBACK,CRH:suppressed,HYPOTHALAMUS,PITUITARY,ADRENAL,ADENOMA,Adrenaladenoma,PLASMACORTISOL,NEGATIVE,FEEDBACK,WilliamE.Winter,MD,ACTH:suppressed,NEGATIVE,FEEDBACK,库欣综合征的诊断,定位诊断明确库欣综合征的病因影象学检查肾上腺B超、CT、MRI131I-胆固醇扫描垂体80-90%为微腺瘤CT、MRI（MRI优于CT）胸片其他部位x线检查,治疗及预后,库欣病经鼻经蝶窦垂体瘤摘除术治愈率80%复发率10%左右垂体放疗肾上腺手术肾上腺瘤-肾上腺瘤手术术后短期补充糖皮质激素,治疗及预后,异位ACTH瘤手术切除肿瘤局部放疗药物治疗密妥坦(O,P-DDD)-抑制皮质醇合成氨基导眠能-抑制皮质醇合成甲吡酮-11羟化酶抑制剂,库欣综合征的药物治疗,80%近期治愈10-30%复发,30-50%未治愈,垂体放射治疗,40%治愈（其中85%为18岁