Streamlined Diagnostic Strategy for Primary Aldosteronism

原发性醛固酮增多症的简化诊断策略

基本信息

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
项目类别：
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

项目摘要

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) 危险因素，困扰 30% 的美国成年人，尽管有多种抗高血压药物，但控制率很低，导致心血管事件、肾衰竭和中风。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患病率为 8-10%，在顽固性高血压患者中患病率为 14-30%。尽管使用醛固酮/肾素比值 (ARR) 可以轻松识别，并且可以随时使用定向疗法进行治疗，但 PA 的筛查率极低（占所有高血压患者的 <0.1%），但由于原因漫长、复杂且困难，因此错过了这一机会。将 PA 准确分型为产生醛固酮的腺瘤（APA，单侧 30% PA）或特发性醛固酮增多症（IHA，双侧，约 65%）对于大多数 APA，建议进行手术，而 IHA 的盐皮质激素受体拮抗剂 (MRA) 是唯一能可靠区分 APA 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手术。通过简单的血液检测来识别可手术治愈的 PA 病例将是高血压治疗的重大进步，特别是难治性高血压患者。我们的基础研究表明，几乎所有 APA 都表达一些类固醇生成酶，但这些酶并不表达。基于这一发现，我们发现 APA 患者的血清中异常的混合类固醇和前体，如 18-羟基皮质醇 (18OHF) 比 IHA 患者的血清中含量更高。生产少量的类固醇，导致重叠和辨别力差。通过结合动态测试（盐水或地塞米松抑制）和使用质谱法进行类固醇分析，我们将识别类固醇和类固醇。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影像学和 AVS 的需求。这项工作将鼓励筛查 PA 并降低成本和风险。拟议试点研究的结果将用于开发测试算法的多中心试验，这将促进这种方法的采用和传播，以改善患者护理和结果。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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

单侧原发性醛固酮增多症肾上腺切除术后的结果：关于国际队列中结果测量和缓解率分析的国际共识。

DOI：
10.1016/s2213-8587(17)30135-3
发表时间：
2017-09
期刊：
The lancet. Diabetes & endocrinology
影响因子：
0
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

Discordance between imaging and immunohistochemistry in unilateral primary aldosteronism.

单侧原发性醛固酮增多症的影像学和免疫组织化学之间的不一致。

DOI：
发表时间：
2017-12
期刊：
影响因子：
3.2
作者：
Nanba, Aya T;Nanba, Kazutaka;Byrd, James B;Shields, James J;Giordano, Thomas J;Miller, Barbara S;Rainey, William E;Auchus, Richard J;Turcu, Adina F
通讯作者：
Turcu, Adina F

Classics in Cardiovascular Endocrinology: Aldosterone Action Beyond Electrolytes.

心血管内分泌学经典：醛固酮超越电解质的作用。