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个独立的以病人为导向的研究者和成功的导师继续专业发展。我最近的研究重点是建立和验证肢端肥大症治疗的最佳生化终点。在这些努力中，我建立了一个独特的大型患者队列，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，我们认识到需要验证针对临床疾病活动性的治疗的生化终点，以确保真正“正常”的临床GH/IGF-I状态。本申请的科学目的是将现代生化标志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R 01 DK 06420资助，我是PI，研究使用身体成分来衡量疾病活动，用新型GH受体拮抗剂pegvisomant治疗，以及生长激素释放肽分泌失调对肢端肥大症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R 01，在目标5中，研究IGF-I水平作为肢端肥大症胰岛素敏感性和身体组成的标志物，在目标6中，研究IGF-I作为GH受体拮抗剂pegvisomant治疗期间心血管结构和功能的标志物。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，NIH资助的临床研究计划和12年的以患者为导向的研究经验使我非常适合获得K24奖。K24提供的额外资金将使我能够提高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，并使我能够继续在这两个领域扩展。哥伦比亚大学的机构环境，拥有强大而多样化的内分泌部门，GCRC，糖尿病和肥胖研究中心，是吸引研究员和开展研究的理想场所。以患者为导向的研究的职业生涯中期研究者奖是一个理想的机制，以确保必要的支持，我需要减少临床和行政责任，并确保我作为导师和临床研究人员的持续成功。

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.