【作者】 吴霞；

【导师】 徐瑞；

【作者基本信息】 山东大学 ， 内科学（心血管病）（专业学位）， 2022， 硕士

【摘要】 研究背景:原发性醛固酮增多症(primary aldosteronism,PA)简称为原醛症,是继发性高血压的常见病因之一,其治疗方式取决于分型诊断。受限于技术等因素,目前临床大多以影像学表现作为判断患者分型的标准,从而选择手术或药物治疗。针对手术治疗的患者,常规病理无法对其进行功能诊断,可能导致患者被漏诊、误诊。研究目的:本研究将探讨影像学表现不同的PA患者的临床特征,并通过免疫组织化学染色探究醛固酮合酶(aldosterone synthase,CYP11B2)及趋化因子受体4(chemokine receptor4,CXCR4)对PA患者病理诊断及分型的价值。研究方法:选取2015年11月至2021年11月期间本院收治的160例原发性醛固酮增多症患者,依据影像学表现分为腺瘤组、增生组和正常组,收集患者资料并进行统计学分析。同时选取39例诊断为PA并且于我院肾上腺手术的患者及5例肾上腺无功能腺瘤患者,对其术后肾上腺组织进行CYP11B2与CXCR4的免疫组织化学染色,并对染色结果进行半定量评分。研究结果:1.160例PA患者平均年龄58.72±11.15岁,好发于51-60岁年龄段,共有60例,占37.5%;病程中位数为10(12)年;102例的患者存在低钾血症(63.75%)。2.影像学表现不同的患者,其年龄、血钾、血浆醛固酮浓度、血浆肾素浓度(plasma aldosterone concentration,PAC)、醛固酮/肾素浓度比值(aldosterone renin ratio,ARR)、血钠及二氧化碳结合力(carbon dioxide combining power,CO2CP)的组间差异比较均有统计学意义(P均<0.05)。而性别、高血压病程、既往病史、血管紧张素Ⅱ、血钙、尿酸、血肌酐、估算的肾小球滤过率、甘油三酯、胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、同型半胱氨酸、空腹血糖、糖化血红蛋白等均无组间差异(P>0.05)。3.腺瘤组的年龄及血钾低于增生组和正常组,PAC、血钠、CO2CP高于增生组,差异均有统计学意义(P均<0.05)。无论是腺瘤组还是增生组,病变部位不同并不影响患者的生化指标,各亚组化验指标均无组间差异(P>0.05)。4.在肾上腺病变部位观察到CXCR4与CYP11B2的特异性染色,且二者染色存在相关性。应用CYP11B2及CXCR4两个指标对PA进行联合诊断,当CXCR4≥2 分,CYP11B2=3 分时,曲线下面积 AUC 为 0.895,P<0.0001,95%置信区间为(0.765-0.967)。灵敏度为97.44%,特异度为80%。5.CYP11B2的免疫组织化学染色对腺瘤和结节样增生的区分无统计学意义。而当CXCR4>1分时,其诊断腺瘤的曲线下面积AUC为0.859,P<0.0001,95%置信区间为(0.711-0.950)。灵敏度为80.77%,特异度为84.62%。研究结论:1.影像学表现为腺瘤的PA患者,临床表现更为典型,血钾和肾素更低,醛固酮和ARR更高。2.不同部位的肾上腺病变对患者的生化指标无显著影响。3.可以应用CYP11B2联合CXCR4免疫组织化学染色对PA患者进行病理诊断,其灵敏度为97.44%,特异度为80%。4.CXCR4的免疫组织化学染色可以对PA患者进行腺瘤及增生的亚型诊断,灵敏度为80.77%,特异度为84.62%,但CYP11B2对这两者的染色无差异。更多还原

【Abstract】 Background:Primary aldosteronism(PA)is one of the common causes of secondary hypertension,and its treatment depends on the subtype diagnosis.Limited by factors such as technology and expense,most of the time,imaging features are used as the criterion for judging the type of PA,which decides whether the patient should be treated with medication or surgery,Routine pathological diagnosis cannot make functional diagnosis of the adrenal gland lesions,which may lead to missed diagnosis and misdiagnosis of patients.Objective:This study will explore the clinical characteristics of PA patients with different imaging manifestations.The value of aldosterone synthase(CYP11B2)and chemokine receptor 4(CXCR4)in the pathological diagnosis and typing of PA patients are also explored by immunohistochemical staining.Methods:A total of 160 patients with primary aldosteronism who were admitted to our hospital from November 2015 to November 2021 were selected and divided into adenoma group,hyperplasia group and normal group according to imaging findings.Patient data were collected and analyzed statistically.At the same time,39 patients who were diagnosed with PA and underwent adrenal surgery in our hospital and 5 patients with adrenal nonfunctioning adenoma were selected,and their postoperative adrenal tissues were subjected to immunohistochemical staining for CYP11B2 and CXCR4,and the staining results were scored semiquantitatively.Results:1.The patients with PA had an average age of 58.72±11.15 years old,and most of them were in the age group of 51-60 years old,with a total of 60 cases,accounting for 37.5%.The median duration of the hypertension was 10(12)years.There were 102 patients with hypokalemia(63.75%).2.There were statistically significant differences in age,serum potassium,plasma aldosterone concentration(PAC),plasma renin concentration(PRC),aldosterone renin ratio(ARR),serum sodium and carbon dioxide combining power(CO2CP)among patients with different imaging manifestations(P<0.05).There were no differences between groups in gender,hypertension course,past medical history,angiotensin Ⅱ,blood calcium,uric acid,serum creatinine,estimated glomerular filtration rate,total cholesterol,triglyceride,low density lipoprotein-cholesterol,high density lipoproteincholesterol,homocysteine,fasting plasma glucose,hemoglobin A1C(P>0.05).3.The age and serum potassium of the adenoma group were lower than the hyperplasia group and the normal group,while the PAC,serum sodium and CO2CP were higher than the hyperplasia group.Both the differences were statistically significant(P<0.05).Regardless of the adenoma group or the hyperplasia group,the different location of the lesion did not affect the biochemical indexes of the patients,and there was no difference in the laboratory indexes of each subgroup(P>0.05).4.The specific staining of CXCR4 and CYP11B2 was observed in adrenal lesions,and there was a correlation between them.The two indicators of CYP11B2 and CXCR4 were used to jointly diagnose PA.When CXCR4≥2 points and CYP11B2=3 points,the area under curve ROC was 0.895,P<0.0001,and the 95%confidence interval was(0.765-0.967).The sensitivity was 97.44%and the specificity was 80%.5.The immunohistochemical staining of CYP11B2 had no statistical significance in the distinction between adenoma and nodular hyperplasia.When CXCR4>1 point,the area under curve ROC for the diagnosis of adenoma was 0.859,P<0.0001,and the 95%confidence interval was(0.7110.950).The sensitivity was 80.77%,and the specificity was 84.62%.Conclusions:1.PA patients with adenomas on imaging have more typical clinical manifestations.,with lower serum potassium and renin,and higher aldosterone and ARR.2.Adrenal lesions in different parts had no significant effect on the biochemical indexes of patients.3.CYP11B2 combined with CXCR4 immunohistochemical staining can be used for pathological diagnosis of PA patients,with a sensitivity of 97.44%and a specificity of 80%4.CXCR4 immunohistochemical staining can be used to diagnose the adenoma and hyperplasia in PA patients,while there was no difference in CYP11B2 staining.更多还原