Streamlined Diagnostic Strategy for Primary Aldosteronism

原发性醛固酮增多症的简化诊断策略

• 批准号: 9027843
• 负责人: RICHARD J. AUCHUS
• 金额: $ 19.38万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9027843
• 关键词: Adoption; Adrenal Gland Neoplasms; Adrenal Glands; Adult; Aldosterone; Algorithms; American; Antihypertensive Agents; Basic Science; Bilateral; Biological Markers; Blood Tests; Cardiovascular system; Cells; Clinical; Complex; Detection; Dexamethasone; Diagnosis; Diagnostic; Diagnostic tests; Discrimination; Disease; Drug Controls; Endocrine; Enzymes; Evaluation; Event; Figs - dietary; Goals; Guidelines; Health; Healthcare; High Prevalence; Hybrids; Hyperaldosteronism; Hypertension; Image; Kidney Failure; Left; Mass Spectrum Analysis; Mineralocorticoid Receptor; Mineralocorticoids; Multicenter Trials; Operative Surgical Procedures; Organ; Patient Care; Patient-Focused Outcomes; Patients; Phenotype; Pilot Projects; Prevalence; Procedures; Production; Protocols documentation; Publications; Renin; Research; Resistant Hypertension; Resources; Risk; Saline; Sampling; Sampling Studies; Secondary Hypertension; Serum; Societies; Steroids; Stroke; Testing; Veins; Work; adenoma; base; biomarker development; blood pressure regulation; cardiovascular risk factor; cost; high risk; improved; medical specialties; novel; patient population; peripheral blood; prevent; research study; screening

 DESCRIPTION (provided by applicant): Hypertension is a treatable major cardiovascular (CV) risk factor, which afflicts 30% of American adults. Despite many classes of antihypertensive drugs, control rates are poor, leading to CV events, renal failure, and stroke. The most common form of secondary hypertension is primary aldosteronism (PA), with a prevalence of 8-10% amongst all hypertensive patients and 14-30% among patients with resistant hypertension. Despite facile identification using aldosterone/renin ratio (ARR) and readily available treatment with directed therapies, screening rates for PA are extremely low (<0.1% of all hypertensives). The reasons for this missed opportunity include the long, complex, and difficult evaluation of PA. Accurate subtyping of PA into aldosterone-producing adenoma (APA, unilateral 30% of PA) or idiopathic hyperaldosteronism (IHA, bilateral, ~65% of PA) is essential to guide treatment. Surgery is recommended for most APAs and mineralocorticoid receptor antagonist (MRA) for IHA. Adrenal vein sampling (AVS) is the only test that reliably distinguishes APA from IHA, but few centers perform this technically challenging procedure well. A simple blood test to identify surgically curable cases of PA would be a major advance in the management of hypertension, particularly patients with resistant hypertension. Our basic research studies have shown that nearly all APAs express some steroidogenic enzymes not normally found in aldosterone-producing cells. Based on that finding, we then showed that unusual hybrid steroids and precursors, such as 18-hydroxycortisol (18OHF) are more abundant in serum from patients with APA than those with IHA. However, the normal adrenal makes small amounts of some of these steroids, leading to overlap and poor discrimination. By combining dynamic testing (saline or dexamethasone suppression) and steroid profiling using mass spectrometry, we will identify steroids and ratios, which reliably distinguish APA from IHA patients. This proposal will develop a clinically useful diagnostic test that will define patients who DO NOT have APAs and eliminate their need for imaging and AVS. This work will encourage screening for PA and reduce the cost and risk of the evaluation. The findings from the proposed pilot studies will be used to develop multi-center trials of the testing algorithm, which will enhance the adoption and dissemination of this approach to improve patient care and outcomes.

 描述（由申请人提供）：高血压是一种可治疗的主要心血管（CV）风险因素，困扰着30%的美国成年人。尽管有许多种类的抗高血压药物，但控制率很差，导致CV事件、肾衰竭和卒中。继发性高血压最常见的形式是原发性醛固酮增多症（PA），在所有高血压患者中的患病率为8-10%，在顽固性高血压患者中的患病率为14-30%。尽管使用醛固酮/肾素比值（ARR）进行鉴别很容易，并且直接治疗也很容易，但PA的筛查率极低（<0.1%）。这种错失机会的原因包括PA的长期，复杂和困难的评估。PA准确分型为醛固酮腺瘤（阿帕，单侧30% PA）或特发性醛固酮增多症（IHA，双侧，约65% PA）对指导治疗至关重要。大多数APA和盐皮质激素受体拮抗剂（MRA）治疗IHA建议手术。肾上腺静脉采样（AVS）是唯一可靠区分阿帕和IHA的测试，但很少有中心能很好地执行这一技术上具有挑战性的程序。一个简单的血液检查，以确定手术可治愈的PA病例将是一个重大的进展，在管理高血压，特别是顽固性高血压患者。我们的基础研究表明，几乎所有的APA表达一些类固醇生成酶，通常不会发现在醛固酮生产细胞。基于这一发现，我们随后发现，阿帕患者血清中不寻常的混合类固醇和前体，如18-羟基皮质醇（18 OHF）比IHA患者更丰富。然而，正常肾上腺产生少量的这些类固醇，导致重叠和差的区分。通过结合动态测试（生理盐水或地塞米松抑制）和使用质谱的类固醇分析，我们将确定类固醇和比例，可靠地区分阿帕和IHA患者。该提案将开发一种临床上有用的诊断测试，该测试将定义没有APA的患者，并消除他们对成像和AVS的需求。这项工作将鼓励筛查PA并降低评估的成本和风险。拟议的试点研究的结果将用于开发测试算法的多中心试验，这将加强这种方法的采用和传播，以改善患者护理和结果。

项目成果

Primary Aldosteronism: Practical Approach to Diagnosis and Management.

• DOI: 10.1161/circulationaha.118.033597
• 发表时间: 2018-08-21
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Byrd JB;Turcu AF;Auchus RJ
• 通讯作者: Auchus RJ

Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort.

单侧原发性醛固酮主义肾上腺切除术后的结局：关于结果测量和分析国际队列中缓解率的国际共识。

• DOI: 10.1016/s2213-8587(17)30135-3
• 发表时间: 2017-09
• 期刊: The lancet. Diabetes & endocrinology
• 作者: Williams TA;Lenders JWM;Mulatero P;Burrello J;Rottenkolber M;Adolf C;Satoh F;Amar L;Quinkler M;Deinum J;Beuschlein F;Kitamoto KK;Pham U;Morimoto R;Umakoshi H;Prejbisz A;Kocjan T;Naruse M;Stowasser M;Nishikawa T;Young WF Jr;Gomez-Sanchez CE;Funder JW;Reincke M;Primary Aldosteronism Surgery Outcome (PASO) investigators
• 通讯作者: Primary Aldosteronism Surgery Outcome (PASO) investigators

Aldosterone Synthase Promoter Polymorphism and Cardiovascular Phenotypes in a Large, Multiethnic Population-Based Study.

醛固酮合酶启动子多态性和心血管表型中的大型，基于多种族的研究。

• DOI: 10.1097/jim.0000000000000220
• 发表时间: 2015-10
• 期刊: Journal of investigative medicine : the official publication of the American Federation for Clinical Research
• 作者: Byrd JB;Auchus RJ;White PC
• 通讯作者: White PC