原发性醛固酮增多症(中英文）

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,原发性醛固酮增多症,广东省人民医院,冯颖青,Forms of primary aldosteronism,Aldosterone-producing adenoma (APA),Bilateral idiopathic hyperplasia (IHA),Primary (unilateral) adrenal hyperplasia,Aldosterone-producing adrenocortical carcinoma,Familial hyperaldosteronism (FH),Glucocorticoid-remediable aldosteronism (FH type I),FH type II (APA or IHA),Number of diagnosed cases of PA per year,The Journal,of,Clinical Endocrinology & Metabolism Vol. 89, No. 3 1045-1050,Prevalence of PA in hypertensive patients,Firstauthor, year,Screening test,Confirmatory test,No.screened,No. with PA (%),Mosso, 2003,PAC/PRA ratio,Fludrocortisone suppression test,609,37 (6.1),Gordon, 1994,PAC/PRA ratio,Dexamethasone suppression test,199,17 (8.5),Abdelhamid, 1996,Urinary aldo sterone and metabolites,Postural stimulation and saline infusion,3900,257 (6.6),Rossi, 1998,Logistic discri minant analysis,NRmetabolites,320,19 (5.9),Lim, 1999,PAC/PRA ratio,PAC(pmol/l)to PRA (ng/ml/h),ratio 750,125,18 (14.4),Loh, 2000,PAC/PRA ratio,Saline infusion suppression test,350,16 (4.6),Percentage of PA patients with hypokalemia,The Journal,of,Clinical Endocrinology & Metabolism Vol. 89, No. 3 1045-1050,only a small proportion,of,patients (between 9,and,37%, depending on the center) were hypokalemic.,A, From 19571985, 248 patients were diagnosed with primary aldosteronism at Mayo Clinic; 57% had surgically confirmed APA, and 11% had probable APA; the remainder (33%) had probable or confirmed bilateral IHA. B, In 1999, 120 patients were diagnosed with primary aldosteronism at Mayo Clinic; 20% had surgically confirmed APA, and 8% had probable APA; the remainder (72%) had probable or confirmed bilateral IHA.,First autho,r, year,Diagnostic tests,No. with PA,No. with APA (%),Grant, 1984,PAC and PRA before and after postural,101,61 (60.4),Weinberger, 1993,PAC after sodium load, PRA after low sodium diet or postural,62,48 (77.4),Blumenfeld, 1994,Aldosterone excretion, PAC and PRA before and after postural stimulation,82,52 (63.4),Rossi, 2001,PAC and PRA before and after dexamethasone,104,41 (39.4),Magill, 2001,Aldosterone excretion, PAC,PRA,62,15 (24.2),Total (%),56.6,bilateral adrenal hyperplasia (2/3 of cases) and aldosterone-producing adenoma (1/3 of cases),Schimenbach, Best Pract Res Clin Endocrinol Metab. 2006 Sep;20(3):369-84,肾上腺皮质病变,Aldo,储NA排K,血容量,PRA,自主性,低K BP,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,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+25mmol / 24h；血，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24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，48am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0.7 mg/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,CT,Comparison of Adrenal Vein Sampling and Computed Tomography in the Differentiation of Primary Aldosteronism,Steven B. Magill, Hershel Raff, Joseph L. Shaker, Robert C. Brickner, Thomas E. Knechtges, Michael E. Kehoe and James W. Findling,Endocrine-Diabetes Center, Departments of Medicine and Radiology, St. Lukes Medical Center, Milwaukee, Wisconsin 53215,Purpose,: compare AVS and CT imaging of the adrenal glands in patients with hyperaldosteronism in whom CT imaging was normal or in whom focal unilateral or bilateral adrenal abnormalities were detected,The diagnosis of primary aldosteronism was made in 62 patients based on an elevated plasma aldosterone to PRA ratio and an elevated urinary aldosterone excretion rate.,38 patients had CT imaging and successful bilateral adrenal vein sampling and were included in the final analysis.,Comparison of CT imaging and adrenal vein sampling,Patient no.,AVS,CT,APA,15,15,8,IHA,21,21,4,PHA,2,Conclusion,: adrenal CT imaging is not a reliable method to differentiate primary aldosteronism. Adrenal vein sampling is essential to establish the correct diagnosis of primary aldosteronism.,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0.1mg q6h，共4天,测定立位ALDO,60pg/dl，,立位PRA ,尿钠的排泄,3,mmol,/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ALDO,5ng/dl，PA确诊。,口服：高钠饮食3天（300mmol钠/d），测定24小时尿ALDO,10g/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35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（60 mg，5次/日），共服710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。,How Should the Clinician Distinguish between IHA and APA?,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95100%。,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：ALDO,side,/ALDO,contra,(A/C,side,)/(A/C,contra,提示APA。,APA:have more severe hypertension, more frequent hypokalemia, higher plasma (25 ng/dl; 694 pmol/liter) and urinary (30 g/24 h; 83 nmol/d) levels of aldosterone, and are younger (15ng/L, Aldo/PRA50,低钾性肾病,如低钾性间质性肾炎、肾小管酸中毒、Fanconi综合征等肾脏疾病，因有明显的肾功能改变及血pH值的变化，且为继发性醛固酮增多，而不难与原醛症进行鉴别。,是一种因肾脏产生分泌肾素的肿瘤而致高肾素，高醛固酮的继发性醛固酮增多症，多见于青少年。测定血浆醛固酮水平及肾素活性，行肾脏影象学检查等则可确诊。,肾素分泌瘤,24小时尿的留法是：第一天早7点排一次尿弃去，然后从7点至第二天早7点，24小时内每次尿均留在一个大容器内，包括第二天7点时的尿，测定24小时的尿量并记录，留10-20ml尿送化验室查K+、Na+、Cl- 等，并在留尿结束的同一天抽血查K+、Na+、Cl- 等电解质。,化验检查,盐皮质激素过多,原醛,糖皮质激素过多,皮质醇增多症,髓质分泌过多,嗜络细胞瘤,长期服用噻嗪类排钾利尿剂的原发性高血压病人，可出现低血钾而不易与原醛症进行鉴别。,停用利尿剂或含利尿剂的降压药24周，观察血钾变化，如为利尿剂引起，则停药后血钾可恢复正常。,详细询问病史及高血压家族史,测定血浆醛固酮、PRA水平，必要时可行肾上腺CT扫描、卡托普利试验等,原发性高血压,故从病史、体征及肾功能化验，血浆Ald、PRA等测定亦不难予以鉴别。此外，肾血流图、肾血管多普勒超声检查、卡托普利肾图、肾动脉造影等均可以帮助确诊肾动脉狭窄。,