Skeletal Consequences of Mild Autonomous Cortisol Secretion

项目总结/摘要 肾上腺腺瘤影响5%-10%的人口，在美国每年发现约400万成年人 States.肾上腺腺瘤患者表现出异常的类固醇分泌和代谢， 普遍被称为“亚临床”轻度自主皮质醇分泌（MACS）。现有证据有限 提示MACS患者椎体骨折的发生率非常高，很多时候与 骨密度下降了解MACS如何影响骨代谢并导致骨折， 显著受限于异质性患者人群和骨疾病的多因素病因。 该项目的总体目标是了解骨折患者的流行病学， 肾上腺肿瘤和MACS，并确定异常类固醇分泌和代谢的元素， 预测骨骼疾病，最终导致骨折。这将通过三个具体目标来实现。在目标1中， 奥姆斯特德县人口将通过罗切斯特流行病学项目（REP）进行访问，以确定 肾上腺肿瘤患者脆性骨折的患病率和发生率，以及 将确定断裂发生时脆性的MACS严重度。目标2中提出的实验将 确定在MACS患者中观察到的异常类固醇代谢组是否与受损的 骨密度、质量、结构和代谢，反过来又与两者的风险增加有关 脊椎和非脊椎骨折。目标3中提出的实验将确定异常 MACS患者皮质醇分泌的昼夜节律与钙代谢异常相关 和骨转换标志物的改变。 拟议的职业发展奖和相关的候选人培训解决了一个重要的健康问题， MACS患者的骨骼健康问题，并为候选人的独立职业生涯做好准备。 研究，满足NIH指导的以患者为导向的研究职业发展奖的目标 （母公司K23 -不允许进行独立临床试验），PA-18-375。特殊的资源和体制 在马约诊所的支持，优秀的多学科指导团队，以及拟议的职业发展 活动将使候选人实现成为独立调查员的长期目标， 类固醇对骨骼健康影响的国家公认专家，并设计有效的干预措施， 改善肾上腺肿瘤患者的骨骼健康。

PROJECT SUMMARY/ABSTRACT Adrenal adenomas affect 5%-10% of the population, discovered annually in about 4 million adults in United States. Patients with adrenal adenomas demonstrate an abnormal steroid secretion and metabolism, the most prevalent being called “subclinical” mild, autonomous cortisol secretion (MACS). Available limited evidence suggests that patients with MACS suffer from very high-rates of vertebral fractures, many times not correlated with deterioration of bone density. Understanding how MACS affects bone metabolism and leads to fractures is significantly limited by heterogeneous patient populations and the multifactorial etiology of bone disease. The overall objective of the proposed project is to understand the epidemiology of fractures in patients with adrenal tumors and MACS, and to identify the elements of abnormal steroid secretion and metabolism that predict bone disease, and ultimately fractures. This will be accomplished in three specific aims. In Aim 1, the Olmsted county population will be accessed through the Rochester Epidemiology Project (REP) to determine the prevalence and incidence of fragility fractures in patients with adrenal tumors overall, and the effect of MACS severity on fragility on fracture occurrence will be established. The experiments proposed in Aim 2 will determine if the abnormal steroid metabolome observed in patients with MACS is associated with impaired bone density, quality, structure and metabolism that, in turn, are associated with an increased risk of both vertebral and non-vertebral fractures. The experiments proposed in Aim 3 will determine if the abnormal circadian pattern of cortisol secretion in patients with MACS is associated with abnormal calcium metabolism and alterations in bone turnover markers. The proposed career development award and associated candidate training address an important health problem of skeletal health in patients with MACS and prepare the candidate for an independent career in research, meeting the goal of the NIH mentored Patient-Oriented Research Career Development Award (Parent K23 - Independent Clinical Trial Not Allowed), PA-18-375. The exceptional resources and institutional support at Mayo Clinic, outstanding multi-disciplinary mentorship team, and proposed career development activities will allow the candidate to achieve her long-term goal of becoming an independent investigator and nationally recognized expert on steroid effects on bone health and design interventions that are effective in improving skeletal health of patients with adrenal tumors.