库欣综合征课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,2018/5/13,#,内分泌性高血压低血钾一库欣综合征,临床药师 张崇,襄阳市第一人民医院,Cushings Syndrome,1912年，Harvey Cushing发现了1例23岁的女性，表现为肥胖、多毛、闭经,20年后，Harvey Cushing提出了由垂体功能异常导致肾上腺增生的“多腺体综合征的概念,随后的数十年里，人们陆续发现了肾上腺肿瘤可导致类似的表现,1962年，发现异位ACTH综合征。随后“Cushings Syndrome被用来描述一系列类似表现的总称,A:,向心性肥胖、水牛背；,B:,满月脸；,C,：多毛、痤疮；,D,：向心性肥胖、满月脸；,E,和,F,：腹部青色条纹；,G,：先天性肾上腺皮质增生用过量地塞米松治疗后；,H,：皮肤变薄，挫伤,A,：股骨头坏死,B,：,股骨头坏死,C,：脊柱塌陷,D,：肋骨骨折,Hirsutism,：多毛症,Psychiatric dysfunction:,精神异常,Backache:,腰痛,Plethora,：血液系统异常,Bruising:,挫伤,Red-purple,striae,：紫红色条纹,Ankle,edema,：踝关节水肿,Pigmentation,：色素沉积,Osteoporosis,：骨质疏松,Renal,calculi,：肾结石,1、水盐代谢失衡的发生机制高血压低血钾：,2、Hypokalemic alkalosis 低血钾性碱中毒is found in 10%to 15%of patients with Cushings disease but in more than 95%of patients with ectopic ACTH syndrome.,3,、,The,functions of the,pituitary-thyroid axis and,the pituitary-gonadal,axis,are suppressed,in patients,with Cushings,syndrome because of a direct effect of cortisol,on TSH and gonadotropin secretion,4,、,Growth hormone secretion,is reduced,1,、,ACTH,依赖性占,7080%,，包括垂体肿瘤和异位,ACTH,综合征；,ACTH,非依赖性占,2030%,，主要为肾上腺肿瘤和肾上腺皮质增生,2,、异位,ACTH,综合征中肺癌占比超过,50%,，以小细胞肺癌为主,如何诊断？,1,、血,ACTH,和皮质醇测定,2、24小时尿游离皮质醇UFC,不受血液皮质醇结合球蛋白浓度的影响，敏感性大91%96%；需至少测定2次,饮水过多5L/d、任何导致皮质醇增多的病理和生理状态下可出现假阳性,中、重度肾功能不全GFR60可出现假阴性,放免法受皮质醇代谢产物和外源性糖皮质激素影响；HPLC-串联质谱法受某些药物影响，如卡马西平和非诺贝特,3,、,Low-Dose,Overnight Dexamethasone,Suppression Tests,原理：在正常人，超生理剂量的地塞米松可抑制ACTH和皮质醇的分泌；而在任何类型的库欣患者，均不能被抑制,方法：午夜1112点口服地塞米松 1 mg，早8:00采血监测皮质醇浓度.A normal response is a plasma cortisol level of less than 140 nmol/L(5 g/dL)between 8 and 9 a.m.the following morning敏感性91%，特异性95%,如果采用50 nmol/L 为介值，敏感性大于95%，单特异性只有80%左右,地塞米松的吸收代谢率不同对结果有影响：CYP3A4诱导剂，苯巴比妥、卡马西平、利福平可导致假阳性；肝肾功能衰竭者地塞米松去除率降低可导致假阴性,检查前测清晨血皮质醇，然后给予地塞米松口服,，,0.5 mg every 6,hours for 48 hours,.,，然后再测,Using,a postdexamethasone,plasma cortisol concentration,of less than 50 nmol/L(2 g/dL),as the,cutoff,point,this,test is reported to have a 97%to,100%true-positive,rate and a false-positive rate of less,than 1%,.,经典方法：,如何诊断？,血钾和碳酸盐,甲吡酮,岩下静脉窦采血,放射性核素扫描,High-Dose Dexamethasone Suppression Test,2 mg dexamethasone every 6 hours for 48 hours and demonstrating a fall of greater than 50%in urinary 17-hydroxycorticosteroids2mg，Q6H，48小时,In the modern test,the plasma or urinary free cortisol(or both)is measured at 0 and+48 hours,and a greater than 50%suppression of plasma cortisol from the basal value has been used to define a positive response下降50%以上为被抑制,About,90%,of patients,with Cushings disease,have a positive,48-hour test,compared,with 10%of those with the ectopic,ACTH syndrome,敏感性,6080%,，特异性,8090%,CRH,刺激试验中库欣和异位,ACTH,综合征的表现,生长抑制受体显像SRS,生长抑制受体是位于细胞膜表现的,G,蛋白偶联受体，有,5,种亚型，分别为,SSTR15,。人工合成的生长抑素类似物，如奥曲肽，可与,SSTR,结合。异位分泌,ACTH,的肿瘤高表达,SSTR2,，给予放射性核素标记的奥曲肽后，可在体内显像。但敏感性较低，仅约,49%,。需用,SPECT,，价格较贵。,Medical Treatment of Cushings Syndrome,病例：,女，38岁，BMI 30.67，腰围92cm，臀围100cm，因“眼睑浮肿伴体重增加1年入院，血压160/105mmHg，甲功TSH 1.09uIU/ml，FT3 1.68pmol/L，FT4 0.68pmol/L；ACTH 1.4ng/L；垂体MRI未见明显异常。病程中无月经紊乱，无纳差乏力。体检无明显阳性体征。,初步诊断：1、垂体前叶功能减退？2、高血压,入院查：,1、TC 6.05mmol/L，HbA1c 5.7%，,2、IGF-1 393ng/ml(109-284)，3、性激素八项+GH：GH 4.087ng/ml；泌乳素27.62ng/ml；硫酸脱氢表雄酮 9.76ug/dl23-266,4、RAAS系统无明显异常,5、肾上腺CT：左肾上腺多发占位,08:00,16:00,24:00,ACTH,（,pg/ml,）,15.2,14.3,13.6,皮质醇（,ug/dl,）,22.47,22.42,20.75,参考,值：,ACTH 0-46,；皮质醇上午，下午,ACTH,（,8:00,）,皮质醇（,8:00,）,前,15.6,29.05,后,13.6,28.76,小剂量地塞米松1mg抑制试验,ACTH,（,8:00,）,皮质醇（,8:00,）,24,小时尿皮质醇,前,15.3,25.7,1855.25,第,1,天,15.5,28.19,2056.75,第,2,天,14.3,27.7,2119.50,大剂量地塞米8mg松抑制试验,手术后复查,08:00,16:00,24:00,ACTH,（,pg/ml,）,14.5,13.8,14.3,皮质醇（,ug/dl,）,1.48,1.17,1.27,24,小时尿皮质醇：,230.58ug/24h,患者感乏力，予强的松,10mg QD1,，,5mg QD5,，口服后好转,出院诊断：非ACTH依赖性皮质醇增多症；左肾结石,病理：左侧肾上腺皮质腺瘤,0328,0329,0330,0331,0401,0402,0403,0404,0405,收缩压,142,140,130,150,130,130,140,130,120,舒张压,96,80,70,80,80,80,70,86,70,0319,0320,0321,0322,0323,0324,0325,0326,0327,收缩压,130,132,138,150,140,142,140,140,157,舒张压,80,70,110,80,80,86,80,80,91,手术后mmHg,手术前mmHg,