New Approaches to Evaluation and Treatment of Acromegaly

描述(由申请人提供)： 这个项目的总体目标是支持我作为一名独立的、以患者为中心的调查员和成功的导师的持续专业发展。我最近的研究重点是为肢端肥大症的治疗建立和验证最佳的生化终点。在这些努力中，我建立了一个独特的大量患者队列，根据高度敏感的GH和IGF-I测量重新定义了其生化标准，并研究了这种疾病的新治疗方法。从这些研究中，我们认识到有必要验证针对临床疾病活动性进行治疗的生化终点，以确保真正的“正常”临床GH/IGF-I状态。这项应用的科学目的是将现代生化标记物与我们队列中的短期和长期临床结果以及代谢和临床疾病活动相关联。前4个目标，由我是PI的R01 DK06420资助，调查使用身体成分来衡量疾病活动，新型生长激素受体拮抗剂聚乙二醇胺的治疗，以及肢端肥大症患者生长激素分泌失调对生化和临床疾病活动标志物的影响。两个新的目标扩展了我的R01，在目标5中，研究IGF-I水平作为肢端肥大症患者胰岛素敏感性和身体组成的标志，在目标6中，研究IGF-I作为GH受体拮抗剂聚乙二醇胺治疗期间心血管结构和功能的标志。这些研究旨在提高我们对最佳治疗终点的理解，特别是我们治疗肢端肥大症的血清IGF-I目标。我富有成效的、持续的、由NIH资助的临床研究计划以及12年以患者为导向的研究经验使我非常适合接受K24奖。K24提供的额外资金将使我能够增加我对NIH研究支持的努力，与我目前致力于以患者为导向的研究和指导的时间相称，并使我能够在这两个领域继续扩大。哥伦比亚大学拥有强大而多样的内分泌科、GCRC、糖尿病和肥胖研究中心，其制度环境非常适合吸引研究员和开展我们的研究。以患者为中心的研究生涯中期研究员奖是一个理想的机制，可以确保我获得必要的支持，以减少临床和管理责任，并确保我作为导师和临床研究人员继续取得成功。

DESCRIPTION (provided by applicant): The overall goal of this project is to support my continued professional development as an independent patient-oriented investigator and successfull mentor. My recent research focus has been to establish and validate optimal biochemical endpoints for the therapy of acromegaly. In these efforts, I have established a uniquely large cohort of patients, re-defined its biochemical criteria based on highly sensitive GH and IGF-I measurements and investigated novel therapeutic approaches to this disease. From these studies, we recognized the need to validate the biochemical endpoints for treatment against clinical disease activity in order to ensure truly "normal" clinical GH/IGF-I status. The scientific aims of this application correlate modern biochemical markers with short and long-term clinical outcomes and with metabolic and clinical disease activity in our cohort. The first 4 aims, funded by R01 DK06420 for which I am the PI, investigate the use of body composition to gauge disease activity, therapy with the novel GH receptor antagonist, pegvisomant, and the effect of dysregulated ghrelin secretion on biochemical and clinical disease activity markers in acromegaly. Two new aims extend those of my R01, investigating, in Aim 5, IGF-I levels as a markers of insulin sensitivity and body composition in acromegaly and in Aim 6, IGF-I as a marker of cardiovascular structure and function during therapy with the GH receptor anagonist, pegvisomant. These studies aim to improve our understanding of the optimal therapeutic endpoints and, in particular, our serum IGF-I goals for the treatment of acromegaly. My productive, ongoing, NIH funded clinical research program and 12 years of experience in patient-oriented research make me well suited to receive the K24 award. The additional funds provided by the K24 would allow me to raise my effort of NIH research support commensurate with the amount of time I currently commit to patient-oriented research and mentoring and also allow me to continue to expand in both these areas. The institutional environment at Columbia University, with a strong and diverse Endocrine Division, GCRC, Diabetes and Obesity Research Centers, is ideal for attracting fellows and conducting our research. The Mid-career Investigator Award in Patient Oriented Research is an ideal mechanism to ensure the necessary support I need to reduce clinical and administrative responsibilities, and ensure my continued success as a mentor and clinical researcher.