原发性醛固酮增多症(中英文)

原发性醛固酮增多症广东省人民医院冯颖青Formsofprimaryaldosteronism•Aldosterone-producingadenoma(APA)•Bilateralidiopathichyperplasia(IHA)•Primary(unilateral)adrenalhyperplasia•Aldosterone-producingadrenocorticalcarcinoma•Familialhyperaldosteronism(FH)•Glucocorticoid-remediablealdosteronism(FHtypeI)•FHtypeII(APAorIHA)NumberofdiagnosedcasesofPAperyearTheJournalofClinicalEndocrinology&MetabolismVol.89,No.31045-1050PrevalenceofPAinhypertensivepatientsFirstauthor,yearScreeningtestConfirmatorytestNo.screenedNo.withPA(%)Mosso,2019PAC/PRAratioFludrocortisonesuppressiontest60937(6.1)Gordon,1994PAC/PRAratioDexamethasonesuppressiontest19917(8.5)Abdelhamid,2019UrinaryaldosteroneandmetabolitesPosturalstimulationandsalineinfusion3900257(6.6)Rossi,2019LogisticdiscriminantanalysisNRmetabolites32019(5.9)Lim,2019PAC/PRAratioPAC(pmol/l)toPRA(ng/ml/h)ratio75012518(14.4)Loh,2000PAC/PRAratioSalineinfusionsuppressiontest35016(4.6)PercentageofPApatientswithhypokalemiaTheJournalofClinicalEndocrinology&MetabolismVol.89,No.31045-1050•onlyasmallproportionofpatients(between9and37%,dependingonthecenter)werehypokalemic.A,From1957–1985,248patientswerediagnosedwithprimaryaldosteronismatMayoClinic;57%hadsurgicallyconfirmedAPA,and11%hadprobableAPA;theremainder(33%)hadprobableorconfirmedbilateralIHA.B,In2019,120patientswerediagnosedwithprimaryaldosteronismatMayoClinic;20%hadsurgicallyconfirmedAPA,and8%hadprobableAPA;theremainder(72%)hadprobableorconfirmedbilateralIHA.Firstauthor,yearDiagnostictestsNo.withPANo.withAPA(%)Grant,1984PACandPRAbeforeandafterpostural10161(60.4)Weinberger,1993PACaftersodiumload,PRAafterlowsodiumdietorpostural6248(77.4)Blumenfeld,1994Aldosteroneexcretion,PACandPRAbeforeandafterposturalstimulation8252(63.4)Rossi,2019PACandPRAbeforeandafterdexamethasone10441(39.4)Magill,2019Aldosteroneexcretion,PAC,PRA6215(24.2)Total(%)56.6•bilateraladrenalhyperplasia(2/3ofcases)andaldosterone-producingadenoma(1/3ofcases)Schimenbach,BestPractResClinEndocrinolMetab.2019Sep;20(3):369-84肾上腺皮质病变Aldo↑储NA排K血容量↑PRA↓自主性低KBP↑机制临床特点1.BP↑:血容量↑,平滑肌内NA↑,Aldo增加血管对NAR的反应.最早最常见,病程进展,BP逐渐↑,轻中度.以DBP↑为主伴头晕,头痛.2.低K血症乏力,软瘫.突然发生,以下肢为主,持续数小时,自行缓解.寒冷,劳累,利尿剂为其诱因.有感觉异常.发作间期不等.3.心律失常4.OGTT下降,胰岛素抵抗5.失K性肾病:低K远曲小管空泡变性肾小管浓缩功能障碍夜尿↑Aldo依赖ACTH,夜间分泌↓储NA↓口干,多饮6.代谢性硷中毒和低血钙.H交换↑细胞内H↑细胞外H↓代碱细胞外游离Ca↓手足抽搐,尿PH碱性.低K一定程度后,启动排NA系统,故很少浮肿.7.GFR↓,尿蛋白↑Conn四条：•高血压•PRA↓，低NA不能激发•Aldo↑，高NA不能抑制•尿17-羟皮质酮和皮质醇正常标准中无低血K，但当高血压合并低血K时，首先考虑原醛。早期常表现为正常血K性原醛。诊断10%的人存在无功能的肾上腺肿块，因此，不能单凭CT诊断。•血清(浆)K+↓、尿K+排量↑•血清(浆)Na+浓度正常或略高于正常•血氯化物浓度正常或偏低。•如血K+3.5mmol/L,尿K+25mmol/24h；血K+3.0mmol/L，尿K+20mmol/24h，则说明肾小管排钾过多•但上述血、尿电解质浓度测定前至少应停服利尿剂2~4周。化验检查•测定卧、立位血浆Ald、PRA及AngII的方法如下：于普食卧位过夜，如排尿则应于次日4am以前，4~8am应保持卧位，于8am空腹卧位取血，取血后立即肌肉注射速尿40mg（明显消瘦者按0.7mg/kg体重计算，超重者亦不超过40mg），然后站立位活动2小时，于10am立位取血。（PST）化验检查•利尿剂、血管紧张素转换酶(ACE)抑制剂、长压定可增加肾素的分泌，而B阻断剂却明显抑制肾素的释放。影像学诊断•MRI对较小的APA的诊断阳性率低于CT扫描，故临床上不应作为首选的定位方法。•B超APA阳性率只有50%，BAH更低。•CT只能发现5-10MM的肿瘤，＜5MM不能分辨CTComparisonofAdrenalVeinSamplingandComputedTomographyintheDifferentiationofPrimaryAldosteronismStevenB.Magill,HershelRaff,JosephL.Shaker,RobertC.Brickner,ThomasE.Knechtges,MichaelE.KehoeandJamesW.FindlingEndocrine-DiabetesCenter,DepartmentsofMedicineandRadiology,St.Luke’sMedicalCenter,Milwaukee,Wisconsin53215•Purpose:compareAVSandCTimagingoftheadrenalglandsinpatientswithhyperaldosteronisminwhomCTimagingwasnormalorinwhomfocalunilateralorbilateraladrenalabnormalitiesweredetected•Thediagnosisofprimaryaldosteronismwasmadein62patientsbasedonanelevatedplasmaaldosteronetoPRAratioandanelevatedurinaryaldosteroneexcretionrate.•38patientshadCTimagingandsuccessfulbilateraladrenalveinsamplingandwereincludedinthefinalanalysis.ComparisonofCTimagingandadrenalveinsamplingPatientno.AVSCTAPA15158IHA21214PHA2•Conclusion:adrenalCTimagingisnotareliablemethodtodifferentiateprimaryaldosteronism.Adrenalveinsamplingisessentialtoestablishthecorrectdiagnosisofprimaryaldosteronism.原醛的筛查•立，卧位的血ARR=ALDO/PRA。各种文献对比值报道不一，25可疑，50可能性大。•如果同时运用下述标准:ALDO/PRA30,ALDO20ng/dl,其诊断原醛的灵敏性为90%，特异性为91%。原醛的确诊FST氟氢可的松0.1mgq6h，共4天测定立位ALDO60pg/dl，立位PRA＜1.0ng/ml尿钠的排泄3mmol/kg/天血K正常。服药4天后10Am的血浆皮质醇必须低于7Am的皮质醇盐负荷试验•静脉和口服•静脉：生理盐水2L，4小时内静注完，测定血ALDO5ng/dl，PA确诊。•口服：高钠饮食3天（300mmol钠/d），测定24小时尿ALDO10µg/d，PA确诊盐负荷试验•高钠试验正常人及高血压病人血钾无明显变化，原醛症患者血钾可降至3．5毫摩尔/升以下安体舒通（螺内脂）试验安体舒通具有竞争性拮抗醛固酮对肾小管的作用，但并不抑制醛固酮的产生，对肾小管也无直接作用，因此只能用于鉴别有无醛固酮分泌增多，而不能区分病因是原发还是继发性。•服安体舒通300mg/d（60mg，5次/日），共服7～10天为试验日，分别于对照日和试验日多次测定血、尿K+、Na+、Cl-CO2结合力，血气分析，血压，夜尿次数等•原醛症病人一般服用安体舒通1周后，尿钾减少、血钾上升、血浆CO2结合力下降，肌无力、四肢麻木等症状改善，夜尿减少，约半数病人血压有下降趋势。HowShouldtheClinicianDistinguishbetweenIHAandAPA?PST•APA分泌自主性，不受肾素-血管紧张素影响。立位后ALDO不上升。•IHA分泌非自主性，对肾素-血管紧张素反应增强，立位后ALDO上升。升幅50%为标准。影像学诊断AVS采用下腔静脉插管分段取血并分测两侧肾上腺静脉ALDO，如操作成功，并准确插入双侧肾上腺静脉，则腺瘤侧ALDO明显高于对侧，其诊断符合率可达95~100%。AVS•肾上腺静脉取血检测是原醛定位以及功能诊断的“金标准”,是PA分型的重要方法•诊断标准：ALDOside/ALDOcontra2.0(A/Cside)/(A/Ccontra)2.0提示APA。•APA:havemoreseverehypertension,morefrequenthypokalemia,higherplasma(25ng/dl;694pmol/liter)andurinary(30µg/24h;83nmol/d)levelsofaldosterone,andareyounger(50yrold)thanthosewithIHASubtypeevaluationofprimaryAldosteronism•Unilateraladrenalectomy