Skeletal Consequences of Mild Autonomous Cortisol Secretion

项目摘要/摘要 肾上腺腺瘤影响了5%-10%的人口，每年在美国约400万成年人中发现 各州。肾上腺腺瘤患者表现出类固醇分泌和代谢异常，大多数 通常被称为“亚临床”的轻度自主皮质醇分泌(MACs)。可获得的证据有限 提示Mac患者的脊椎骨折发生率很高，很多时候没有相关性。 伴随着骨密度的恶化。了解Mac是如何影响骨代谢并导致骨折的 明显受限于不同的患者群体和骨病的多因素病因。 拟议项目的总体目标是了解慢性阻塞性肺疾病患者骨折的流行病学 肾上腺肿瘤和巨噬细胞瘤，并确定类固醇分泌和代谢异常的因素 预测骨骼疾病，并最终预测骨折。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)获得，以确定 肾上腺肿瘤患者脆性骨折的患病率和发生率，以及 将建立关于骨折发生时脆性的MACS严重程度。目标2中提出的实验将 确定MACS患者中观察到的类固醇代谢异常是否与受损有关 骨密度、骨质量、骨结构和新陈代谢，进而增加两者的风险。 脊椎和非脊椎骨折。目标3中提出的实验将确定是否异常 Mac患者皮质醇分泌昼夜节律与钙代谢异常相关 以及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 Mac患者的骨骼健康问题，并为独立职业生涯做好准备 研究，达到NIH以患者为导向的研究事业发展奖的目标 (Parent K23-不允许进行独立临床试验)，PA-18-375。非同寻常的资源和制度 在梅奥诊所的支持，杰出的多学科导师团队，以及拟议的职业发展 活动将使候选人能够实现她成为独立调查员的长期目标，并 国家公认的类固醇对骨骼健康的影响和设计有效干预措施的专家 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.