CYP11B2/B1基因多态性与醛固酮瘤术后持续性高血压的相关性研究

目的:研究醛固酮合酶基因(CYP11B2)和11-β羟化酶基因(CYP11B1)多态性与醛固酮瘤(Aldoste-rone-producing adenoma,APA)术后持续性高血压的相关性.方法:对电话随访到的2002～2007年在同济医院就诊的93例APA患者采用Taqman探针法检测DNA多态性,包括CYP11B2基因的rs1799998、rs4539及CYP11B1基因的rs6410和rs6387;采用两对独立的PCR检测CYP11B2基因intron2多态性(野生型/转位型),分析上述位点与预后(血压恢复好/坏)的关系.结果:rs4539与术后高血压相关(P=0.008),校正性别、年龄、身体质量指数后仍相关(P=0.002).单体型分析表明,整体上CYP11B2-CYP11B1单体型与术后持续性高血压相关(Global sire,P=0.035).多元回归模型表明,除了传统的风险因素包括术前较长的高血压持续时间、高血压家族史外,单体型H2[OR 1.363(95%CI 1.094～1.689)]、H3[OR 1.555(95%CI 1.148～2.107)]是术后持续性高血压的风险因素,且术前收缩压与单体型H2、H3对术后高血压有协同促进作用(均P<0.005).结论:APA患者术后血压恢复受到CYP11B2/B1多态性的影响,术前尽早控制血压有助于术后血压的恢复.     

CYP1182／B1基因多态性与醛固酮瘤术后持续性高血压的相关性研究

目的：研究醛固酮合酶基因（CYP11B2）和11-β羟化酶基因（CYP11B1）多态性与醛固酮瘤（Aldoste—rone-producing adenoma,APA）术后持续性高血压的相关性。方法：对电话随访到的2002～2007年在同济医院就诊的93例APA患者采用Taqman探针法检测DNA多态性,包括CYP11B2基因的rs1799998、rs4539及CYP11B1基因的rs6410和rs6387;采用两对独立的PCR检测CYP11B2基因intron2多态性（野生型／转位型）,分析上述位点与预后（血压恢复好／坏）的关系。结果：rs4539与术后高血压相关（P=0．008）,校正性别、年龄、身体质量指数后仍相关（P=0．002）。单体型分析表明,整体上CYP11B2-CYP11B1单体型与术后持续性高血压相关（Globalsire,P=0．035）。多元回归模型表明,除了传统的风险因素包括术前较长的高血压持续时间、高血压家族史外,单体型H2[OR 1．363（95％CI1．094～1．689）]、H3EOR1．555（95％CI 1．148～2．107）]是术后持续性高血压的风险因素,且术前收缩压与单体型H2、H3对术后高血压有协同促进作用（均P〈0．005）。结论：APA患者术后血压恢复受到CYP11B2／B1多态性的影响,术前尽早控制血压有助于术后血压的恢复。     

原发性醛固酮增多症诊断和治疗进展

原发性醛固酮增多症(primary aldosteronism，PA，简称原醛症)是肾上腺皮质球状带发生病变时，分泌过量的醛固酮，使人体内分泌代谢产生一系列紊乱现象，典型表现为特征性高血压、低血钾、高醛固酮分泌及低肾素血症的综合征。自1955年Conn首次报告以来，对该病的诊断和治疗已取得了长足进步。     

原发性醛固酮增多症的后腹腔镜治疗

目的：探讨腹膜后腹腔镜治疗原发性醛固酮增多症（primary aldosteronism,PHA）的应用。方法：2002年1月-2009年1月,我院对211例（男109例,女102例）PHA患者行腹膜后腹腔镜手术治疗,其中肾上腺醛固酮腺瘤（APA）113例,单侧肾上腺增生（UNAH）62例,特发性醛固酮增多症（IHA）36例。结果：211例手术均获得成功,无严重并发症发生,手术时间35～360（119．32±58．65）min,出血量10～200（52．85±49．41）ml,住院天数5～14天,术后随诊1～7（2．50±1．58）年,血压恢复正常73例,血压明显改善83例,55例患者术后仍存在高血压,总改善率为74％。结论：应用后腹腔镜治疗PHA安全、有效。     

原发性醛固酮增多症的诊疗进展

原发性醛固酮增多症(primary aldosteronism,PA)是由于肾上腺皮质球状带功能紊乱导致的醛固酮分泌增加所引起的一类内分泌系统疾病。目前,PA已被公认为继发性高血压的最常见形式。PA患者体内过高的醛固酮水平可导致相应的靶器官损害,其严重心血管事件的发生率远高于原发性高血压患者。因此,对PA患者的早期发现和诊断、治疗尤为重要。本文就近年来PA的最新诊疗进展作一综述。     

原发性醛固酮增多症的围手术期处理

目的：探讨原发性醛固酮增多症的围手术期处理的治疗效果。方法：回顾性分析本院1994年1999年经手术治疗的23例原发性醛固酮增多症病例。结果：本组23例在妥善的围手术期处理的配合下安全度过手术关。术后血压恢复正常19例，需继续服用安体舒通降压4例，结论：妥善的围手术期处理对于本症治疗成功至关重要。     

原发性醛固酮增多症手术治疗的研究进展

确诊醛固酮腺瘤和单侧肾上腺增生的原发性醛固酮增多症患者首选手术治疗。手术治疗的目的是切除肾上腺醛固酮高分泌组织,改善预后,选择肾上腺全切术还是部分切除术,尚存争议。本文对不同术式治疗原发性醛固酮增多症的疗效、安全性、术后皮质醇水平、术后复发及手术技术等情况进行探讨。     

原发性醛固酮增多症146例临床分析

目的提高原发性醛固酮增多症的诊治水平。方法分析１９７８～１９９８年收治的原发性醛固酮增多症１４６例,其中肾上腺腺瘤１１１例（７６％）,肾上腺增生３５例（２４％）,均经手术和病理证实。结果术后肾上腺腺瘤８２例（８２／１１１）,肾上腺增生１６例（１６／３５）,血压恢复正常,所有病人血钾均恢复正常。结论正确的治疗取决于正确的定性诊断,分型和定位诊断,Ｂ超和ＣＴ是原醛症定位诊断的主要方法,开放性手术是主要的治疗手段。影响疗效的因素,主要与患者年龄大、病史长、周身血管硬化有关。     

11β-羟化酶缺陷症遗传学研究现状

先天性肾上腺皮质增生症(CAH)是一组常染色体隐性遗传病,11β-羟化酶缺陷症是其第二常见类型,由CYP11B1基因突变导致。先天性CYP11B1基因缺陷使11-β羟化酶活性减弱或丧失,皮质醇合成受阻,合成皮质醇的前体物质大量堆积,血清学以11-去氧皮质酮(DOC)、17-羟孕酮、雄激素水平升高为特征,相应的出现低肾素性高血压、低血钾、女性男性化等主要临床表现。近年来,对CYP11B1基因的突变位点及其功能的研究逐渐增多。本文简述目前11β-羟化酶缺陷症的病理生理机制、临床表现以及分子遗传学研究现状。     

原发性醛固酮增多症的诊断与治疗(附28例报告)

目的:探讨原发性醛固酮增多症(PA)的诊断和治疗。方法:分析1988～1997年外科治疗的PA28例,其中肾上腺皮质腺瘤25例,肾上腺皮质增生3例。结果:25例肾上腺皮质腺瘤患者全部治愈,3例肾上腺皮质增生患者术后仍需服用安体舒通治疗。结论:安体舒通试验、血醛固酮测定是PA的主要定性诊断方法,血醛固酮体位试验和影像学检查有助于肾上腺皮质腺瘤和增生的鉴别;PA的定位诊断主要依靠B超和CT检查,其准确率分别为80%和100%。外科手术是治疗PA的重要方法。     

腹膜后腹腔镜手术与开放手术治疗原发性醛固酮增多症的对比研究

目的:探讨原发性醛固酮增多症(原醛症)行腹膜后腹腔镜手术治疗的效果并与开放手术对比分析。方法:回顾分析行腹膜后腹腔镜手术的原醛症患者36例与近期开放手术治疗的原醛症患者32例的临床效果。结果:后腹腔镜组除平均手术时间外,平均失血量、术后止痛剂用量、术后下床活动时间及术后住院天数均显著优于开放组,无一例需要输血和发生严重并发症。术后平均随访6个月,全部病例均达到治疗目的,无远期手术并发症发生。结论:治疗原醛症采用后腹腔镜手术显著优于开放手术,是一种安全有效的术式,具有患者创伤小、出血少、康复快、住院时间短等优点。     

后腹腔镜手术治疗原醛症(附90例报告)

目的探讨原醛症的后腹腔镜微创手术治疗,并与开放手术作对比分析. 方法原醛症患者90例92侧,行后腹腔镜手术,与近期开放手术治疗的30例患者的各项临床指标进行比较. 结果腔镜组92例侧手术成功91例侧,平均手术时间93 min,开放组114 min;腔镜组术中平均出血36 ml,开放组87 ml;腔镜组术后1.6 d排气,开放组3.1 d;腔镜组术后2.1 d下地活动,开放组3.3 d;腔镜组术后平均住院6.8 d,开放组11.0 d,两组各项指标差异均有显著性意义,P<0.05. 结论与开放手术相比,治疗原醛症采用后腹腔镜微创手术具有创伤小、出血少、恢复快、住院时间短等优点.     

Hypertensive crisis during the resection of an adrenal tumor in primary aldosteronism

Primary aldosteronism is one of the few causes of hypertension which is subject to total surgical treatment, but a hypertensive crisis can occur during the resection of the adrenal tumor. We undertook this study to evaluate the relationship between hormonal factors and a hypertensive crisis during surgery. Sixteen patients with primary aldosteronism who were scheduled for the resection of an adrenal tumor were participated in this investigation. Hormonal factors and hemodynamic variables were evaluated before induction of anesthesia, after induction of anesthesia, 30 minutes after the incision, during tumor manipulation, during resection, and immediately after surgery. During tumor manipulation, a hypertensive crisis occured in six patients (hypertensive group; HG) but not in any others (non-hypertensive group; NHG). There were no differences in hormonal levels, except epinephrine, during tumor manipulation between HG and NHG. Hemodynamic evaluations revealed an increase of systemic vascular resistance during the hypertensive crisis. We conclude that the hypertensive crisis during the manipulation of an adrenal tumor is caused by the rapid release of epinephrine from the manipulated adrenal gland.(Otsuka H, Imai M, Kemmotsu O: Hypertensive crisis during the resection of an adrenal tumor in primary aldosteronism, J Anesth 7: 139–144, 1993)     

应用ROC曲线评价醛固酮肾素比值对原发性醛固酮增多症诊断的临床意义

目的应用接受者操作特性曲线（ROC曲线）选择术前诊断原发醛固酮增多症（原醛症）的醛固酮肾素比值（ARR）的最佳切点,并探讨醛固酮肾素比值在诊断原醛症方面的临床意义。方法从2004年1月到2007年6月在同济医院行手术治疗的肾上腺肿瘤病例133例分为总原醛症组、醛固酮瘤组、肾上腺增生组和非原醛组,用ROC工作曲线选择醛固酮肾素比值的最佳切点。结果总原醛症组和醛固酮瘤组的醛固酮肾素比值的最佳切点为40,而肾上腺增生组的最佳切点为20,醛固酮肾素比值与肾素活性（r=-0.615,P〈0.01）和血管紧张素Ⅱ（r=-0.527,P〈0.01）有负相关性。结论运用醛固酮肾素比值来诊断原醛有很大价值,但还存在不足。     

Coexistence of three distinct adrenal tumors in the same adrenal gland in a patient with primary aldosteronism and preclinical Cushing's syndrome

A 62-year-old woman was admitted to our hospital because of hypokalemia. Physical examination revealed no signs of excessive adrenocortical steroid production, as are found in Cushing's syndrome. Her plasma renin activity (PRA) was suppressed (0.10 ng/ml per h), and her serum aldosterone level was high (30.0 ng/dl). PRA was not increased after a renin-releasing test. Her plasma adrenocorticotropic hormone (ACTH) level was low (<5 pg/ml), but her serum cortisol level was normal (21.0 μg/dl). Administration of 8 mg dexamethasone did not suppress her plasma cortisol level. Finally, she was diagnosed with clinical primary aldosteronism associated with preclinical Cushing's syndrome. Magnetic resonance image revealed three sequential nodular masses (each 15 mm × 15 mm) in the right adrenal gland. A right adrenalectomy was performed by endoscopy. The three removed tumors appeared to have different characteristics. Microscopic examination revealed that the upper and lower tumors were adrenocortical adenomas, and the middle tumor was a black adenoma. Immunohistochemical staining for the enzymes involved in cortisol biosynthesis suggested that the upper tumor secreted aldosterone, whereas either or both of the two other tumors secreted cortisol. Surprisingly, at 33 years of age, she had been diagnosed with Cushing's syndrome, due to a cortisol-producing adrenocortical adenoma, and she had received a left adrenalectomy. Clinically and pathophysiologically, this was a very rare case.     

Correlation between aldosterone synthase gene -344C/T polymorphism and early renal damage in Han population with essential hypertension

Objective To investigate the distribution of aldosterone synthase gene -344C/T polymorphism in patients with essential hypertension in Chinese Han population, and the association with hypertensive early renal damage. Methods Four hundred and eighteen essential hypertension cases in Shandong Provincial Qianfoshan Hospital from January 2012 to January 2015 were included in this study. According to urinary albumin/creatinine ratio, 182 cases were selected as hypertensive early renal damage group (RD group) and 236 essential hypertension without renal damage group (NRD group). Fast venous blood was collected to detect aldosterone synthase gene -344C/T polymorphism and blood lipids, blood glucose, aldosterone and other indicators. Results There were significant differences in genotype frequency and allele frequency distribution between RD group and NRD group (P＜0.05). The TT genotype and the T allele frequency in RD group were higher than those in NRD group (P＜0.05). The level of aldosterone in TT genotype was higher than that in CC and CT genotype (P＜0.05). The aldosterone synthase gene -344C/T polymorphism was not correlated with early renal damage in hypertension after correction of blood pressure (P＞0.05). Conclusions Aldosterone synthase gene -344C/T polymorphism is associated with hypertensive early renal damage. T allele is inclined to hypertensive early renal damage. Aldosterone synthase gene -344C/T polymorphism induces renal damage through elevated blood pressure.     

Experience of retroperitoneoscopic adrenalectomy in 195 patients with primary aldosteronism

OBJECTIVES: Laparoscopic adrenalectomy has become an effective option for aldosteronoma. We evaluated the retroperitoneal approach with regard to safety, efficacy, invasiveness and cost-benefit ratio in patients with primary aldosteronism. METHODS: Between July 1999 and June 2005, we carried out a total of 195 retroperitoneoscopic adrenalectomies (RA) in one hospital, including 108 on the left and 87 on the right, in 78 men and 113 women aged 20-78 years (mean age 48.2 years) with aldosteronoma. Average adrenal tumor size was 16 mm (range 10-32 mm). The 195 operations were divided into 10 groups of 20 operations each, and the mean duration and estimated blood loss for each group were compared. RESULTS: The mean operating time and intraoperative blood loss in RA were 93.2 +/- 37.4 (45-210) min and 68.5 +/- 53.2 (5-210) mL, respectively. Compared to group 1 (cases 1-20), a statistically significant decrease in operative time and estimated blood loss were seen in and after group 4 (>or= case 61, 94.5 +/- 30.3 vs 139.2 +/- 44.7 min, P < 0.01), and in and after group 5 (>or= case 81, 67.5 +/- 50.5 vs 120.5 +/- 60.9 mL, P < 0.01), respectively. No differences were found in duration of surgery and estimated blood loss between left and right sided tumors (P > 0.05). The mean postoperative hospital stay was 4.5 +/- 1.2 days. Postoperative complications, including hematoma and wound infection, occurred in 4.1% of patients. CONCLUSIONS: Retroperitoneoscopic adrenalectomy for aldosteronoma is a safe, effective, and minimally invasive approach with an advantageous cost-benefit ratio. With accumulated experience, it can expedite the learning curve for RA.     

单侧肾上腺切除治疗原发性醛固酮增多症对侧肾上腺储备功能的评价分析

目的对比分析原发性醛固酮增多症(PHA)患者单侧肾上腺切除前后肾上腺皮质分泌功能变化,评估分析单侧肾上腺切除后对侧肾上腺皮质储备功能。方法选取2006年1月至2013年2月接受单侧肾上腺切除手术的42例患者的临床资料。对患者手术前后早晨空腹血皮质醇、促肾上腺皮质素(ACTH)水平、以及促肾上腺皮质激素兴奋1mg地塞米松抑制试验结果进行了有效的统计学分析。结果 42例患者均无出现肾上腺皮质功能不全。手术前后基础皮质醇水平无明显差异。然而,单侧肾上腺切除术后基础ACTH水平明显提高。促肾上腺皮质激素兴奋1mg地塞米松抑制试验的皮质醇峰值水平明显下降。术后皮质醇峰值水平约为术前82.7%(76.0%~91.4%)。结论不伴有皮质醇增多症或亚临床型皮质醇增多症的PHA患者行单侧肾上腺切除,术后血皮质醇水平可维持在正常范围之内,但肾上腺皮质储备功能出现不同程度的下降,其储备功能不低于术前80%,足以使患者术后不会出现肾上腺皮质功能不全。