Non-Classical Manifestations of Primary Hyperparathyroidism

原发性甲状旁腺功能亢进症的非典型表现

• 批准号: 8462595
• 负责人: SHONNI J SILVERBERG
• 金额: $ 17.12万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8462595
• 关键词: 25-hydroxyvitamin D; Address; Affect; Area; Award; Beds; Biochemical; Biomechanics; Biopsy; Bone Density; Bone remodeling; Calcium; Cardiology; Cardiovascular Abnormalities; Cardiovascular Diseases; Cardiovascular Manifestation; Cardiovascular system; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Cognitive; Commit; Data; Development; Discipline; Disease; Disease of parathyroid glands; Educational Curriculum; Educational process of instructing; Educational workshop; Endocrine; Endocrine Surgical Procedures; Endocrinology; Environment; Event; Faculty; Fellowship; Fellowship Program; Foundations; Fright; Functional Magnetic Resonance Imaging; Funding; Future; Goals; Grant; Guidelines; Health; Heart Hypertrophy; Hypercalcemia; Hyperparathyroidism; International; Investigation; Knowledge; Label; Lead; Learning; Left Ventricular Mass; Light; Master of Science; Measures; Medial; Medical; Medical Students; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Metabolic Bone Diseases; Mid-Career Clinical Scientist Award (K24); Midcareer Investigator Award in Patient-Oriented Research; Minor; Neurocognitive; Neurology; Obesity; Organ; Osteogenesis; Outcome; Parathyroidectomy; Pathogenesis; Patients; Persons; Productivity; Program Development; Public Health Schools; Recommendation; Reporting; Research; Research Personnel; Role; Serum; Site; Skeleton; Societies; Stimulus; Stroke; Structure; Techniques; Thick; Time; Training; United States National Institutes of Health; Universities; Vitamin D; Vitamin D Deficiency; Work; bariatric surgery; base; bone; brain metabolism; career; clinical application; clinically relevant; design; hypercalciuria; improved; indexing; innovation; interest; malignant parathyroid gland tumor; medical schools; mortality; neuropsychological; patient oriented; patient oriented research; programs; skeletal; skills; success; symposium; tool

DESCRIPTION (provided by applicant): The central goal of this K24 renewal application is to further my development as a clinical investigator, while enhancing my opportunities and skills in the mentorship of fellows and promising young faculty interested in careers in clinical research. Patient-oriented clinical research has been the cornerstone of my medical career. My main research focus has been the investigation of asymptomatic primary hyperparathyroidism (PHPT). In recent years, my research has concentrated on the non-classical manifestations of PHPT, and the studies in this thematically related K24 program are focused in this area. My research goal is to continue to develop this program. All three themes of this renewal application were highlighted by the 3rd International Workshop on Asymptomatic PHPT (J Clin Endocrinol Metab 94:335-9, 2009) as key areas for future investigation. The themes and Specific Aims (SA's) of this research are: Theme 1. Vitamin D deficiency in PHPT: SA1a. To compare biochemical and skeletal features of PHPT patients with and without co-existing vitamin D deficiency. SA1b. To investigate the early effects of vitamin D repletion in PHPT on static and dynamic histomorphometric parameters of bone remodeling (by quadruple labeled bone biopsy). Theme 2. Cardiovascular manifestations of PHPT: SA2a. To determine whether or not abnormalities in cardiovascular structure or function in patients with asymptomatic PHPT are reversible after parathyroidectomy. SA2b. To investigate the hypothesis that some of the cardiovascular manifestations of PHPT are due to low vitamin D levels, rather than elevated calcium and PTH levels, by comparing left ventricular mass index and carotid intima medial thickness in PHPT patients with and without vitamin D deficiency. Theme 3. Neurocognitive manifestations of PHPT SA3a. To further investigate neurocognitive abnormalities in PHPT by assessing site-specific changes in brain metabolism after parathyroidectomy using the innovative technique of functional MRI. SA3b. To determine whether the neuropsychological abnormalities seen in hypercalcemic PHPT are present in normocalcemic PHPT. Although outside of the closely-knit theme of the K24, there are other ongoing and future opportunities for mentored research (i.e. theme: obesity/bariatric surgery and the skeleton: 3 mentored studies ongoing). Importantly, the proposal will provide many opportunities to mentor junior investigators. I have had success as a mentor, with 16 current or past trainees, 10 of whom have been mentored under the current K24 award. Seven of the 10 remain in academic medicine. Of those I have mentored, 3 currently hold and 1 recently completed NIH K23 Awards, 3 completed Masters in POR (2 under my mentorship) and 2 received Endocrine Fellows Foundations grants. One mentee, who has worked with me since her fellowship began, was awarded a NIH stimulus grant. As Co-Director of our NIH Postdoctoral Fellowship Program and Director of the 4th yr Endocrinology Elective in the medical school, I have ongoing access to medical students, residents, Endocrine Fellows and junior faculty who are interested in my research. There has also been interest in my research from trainees in other disciplines (current cardiology fellow Iwata), enhancing my potential to add interdisciplinary perspectives to POR in metabolic bone diseases that should enhance our field. My mentorship goals for this K24 are both to have the opportunity to mentor, and to further develop my mentorship skills. New directions for mentorship will include: 1. I will develop a new program to educate mentors in the Department of Medicine; creating a curriculum for developing mentoring skills and convening mentors to share and refine best practices. 2. I will expand my mentoring in new directions: a) outside of my research area as a Mentor in the Department of Medicine Faculty Development Program; and b) within my research area but outside of Columbia in online mentorship programs (ASBMR Mentor Matching program and The Endocrine Society's Mentor Exchange). I will develop new mentorship skills, learning to transmit critical information electronically rather than in person and by example. 3. Coursework at Columbia on: mentoring, FDA regulated research and research with minors will sharpen and expand my tools for mentoring. The environment at Columbia is outstanding, with a large and supportive Endocrine Division, an excellent NIH funded Clinical Research Center and CTSA, which offers my mentees the opportunity for didactic enrichment in POR through their Master of Science in POR program (Columbia University Mailman School of Public Health and CTSA). Both the Department of Medicine and the GCRC have made substantial commitments toward my development as a clinical investigator. The initial K24 funding period allowed me to reduce my clinical, administrative and teaching loads in order to devote more time to clinical research and to training and mentoring junior faculty and fellows. This award remains an ideal mechanism to allow me to achieve my dual goals: continued productivity in the clinical investigation of parathyroid disease, with protected time for mentoring fellows and junior colleagues interested in patient oriented clinical research as a career path.

描述（由申请人提供）：此K24更新申请的核心目标是进一步发展作为临床研究者的发展，同时增强了我在研究员的指导中的机会和技能，并有前途的年轻教师对临床研究的职业感兴趣。以患者为导向的临床研究一直是我医疗生涯的基石。我的主要研究重点是研究无症状的原发性甲状旁腺功能亢进（PHPT）。近年来，我的研究集中在PHPT的非古典表现上，并且该主题相关的K24计划的研究集中在该领域。我的研究目标是继续制定该计划。第三次国际无症状PHPT（J Clin Clin Endocrinol Metab 94：335-9，2009）的第三次国际研讨会强调了这一续签应用的所有三个主题，作为未来研究的关键领域。这项研究的主题和特定目的（SA）是：主题1。PHPT中的维生素D缺乏：SA1A。比较具有和没有共存维生素D缺乏的PHPT患者的生化和骨骼特征。 sa1b。为了研究pHPT中维生素D的早期对骨重塑的静态和动态组织形态计量参数的早期作用（通过标记为骨骼活检的四核）。主题2。PHPT的心血管表现：SA2A。为了确定无症状PHPT患者心血管结构异常或功能是否在甲状旁腺切除术后可逆。 SA2B。为了研究PHPT的某些心血管表现的假设是由于维生素D水平较低而不是钙和PTH水平升高引起的，通过比较有或没有维生素D缺乏症的PHPT患者的左心室质量指数和颈动脉内膜厚度。主题3。PHPT SA3A的神经认知表现。通过使用功能性MRI的创新技术来评估甲状旁腺切除术后脑代谢的位点特异性变化，以进一步研究PHPT的神经认知异常。 SA3B。为了确定在高钙血症PHPT中是否存在神经心理学异常，在正常血症PHPT中。尽管在K24的紧密联系的主题之外，但仍在进行其他持续的和未来的研究机会（即主题：肥胖/减肥手术和骨骼：3个持续的研究）。重要的是，该提案将为指导初级调查人员提供许多机会。我作为一名导师取得了成功，有16名现任或过去的学员，其中10名受到当前K24奖的指导。 10个中的7个仍然是学术医学。在我指导的那些人中，目前有3个持有，最近完成了NIH K23奖项，3个完成了POR的硕士学位（我的指导下2个），2个获得了内分泌研究员基金会的赠款。自从她的奖学金开始以来，一位与我合作的受训者获得了NIH刺激奖学金。作为我们NIH博士后奖学金计划的联合导演，以及医学院第四年内分泌选修课的主任，我一直在与我的研究感兴趣的医学生，居民，内分泌研究员和初级教师持续接触。其他学科（当前心脏病学研究员）对我的研究也引起了我的兴趣，从而增强了我增加跨学科观点的潜力，从而在代谢骨疾病中提高了应该增强我们领域的代谢骨骼疾病。我对这款K24的指导目标都有机会指导，并进一步发展我的指导能力。指导的新指导将包括：1。我将制定一项新计划，以教育医学系的导师；创建一个课程，以发展指导技能和召集导师，以共享和完善最佳实践。 2。我将在新方向上扩展我的指导：a）在我的研究领域之外担任医学系发展计划的导师； b）在我的研究领域内，但在哥伦比亚以外的在线指导计划（ASBMR导师匹配计划和内分泌学会的导师交流）。我将发展新的指导技巧，学习以电子方式传输关键信息 比亲自和举例。 3。在哥伦比亚的课程：指导，FDA对未成年人进行研究和研究将使我的指导工具锐化并扩大我的工具。哥伦比亚的环境非常出色，拥有大型且支持性的内分泌部门，这是一家出色的NIH资助的临床研究中心和CTSA，这为我的受训者提供了通过其POR POR计划（哥伦比亚大学邮政公共卫生学院公共卫生和CTSA）进行教学富集的机会。医学系和GCRC都对我作为临床研究者的发展做出了重大承诺。最初的K24资金期使我减少了临床，行政和教学负荷，以便将更多时间用于临床研究，并培训和指导初级教师和研究员。该奖项仍然是让我实现双重目标的理想机制：在甲状旁腺疾病的临床研究中持续生产力，并保护了指导研究员和对患者面向临床研究感兴趣的初级同事的保护时间。