Skeletal Consequences of Mild Autonomous Cortisol Secretion

轻度自主皮质醇分泌对骨骼的影响

基本信息

批准号：
10405659
负责人：
Irina Bancos
金额：
$ 15.71万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-19 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10405659
关键词：
Address Adrenal Gland Adenoma Adrenal Gland Neoplasms Adrenalectomy Adult Affect Androgens Biological Markers Body Composition Bone Density Bone Diseases Bone remodeling Circadian Dysregulation Circadian Rhythms Clinic Clinical Trials County Coupled Data Deterioration Diagnosis Elements Epidemiology Etiology Excretory function Foundations Fracture Functional disorder Glucocorticoids Goals Health Hormonal Hydrocortisone Impairment Incidence Individual K-Series Research Career Programs Mentored Patient-Oriented Research Career Development Award Mentorship Metabolism Multicenter Studies Parents Patients Pattern Population Prevalence Publishing Reporting Research Research Personnel Resources Retrospective Studies Risk Severities Site Spinal Fractures Steroids Structure Time Training United States United States National Institutes of Health base bone fragility bone health bone metabolism bone quality bone strength bone turnover calcium metabolism career career development circadian cohort density effective intervention experimental study fragility fracture high risk improved meetings metabolome multidisciplinary novel patient population population based prospective restoration skeletal spine bone structure steroid metabolism therapy design therapy development urinary

项目摘要

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.

项目摘要/摘要肾上腺腺瘤影响5％-10％的人口，每年在美国大约400万成年人中发现国家。肾上腺腺瘤患者表现出异常的类固醇分泌和代谢，是最多的普遍称为“亚临床”温和的自主皮质醇分泌（MAC）。可用的有限证据表明Mac患者患有非常高的椎骨骨折的患者，许多次不相关定义骨密度。了解MAC如何影响骨骼代谢并导致骨折的是由异质性患者人群和骨病的多因素病因受到明显限制。拟议项目的总体目的是了解患有骨折的流行病学肾上腺肿瘤和Mac，并确定异常类固醇分泌和代谢的元素预测骨骼疾病，并最终骨折。这将以三个具体目标来实现。在AIM 1中奥尔姆斯特德县人口将通过罗切斯特流行病学项目（REP）访问总体上肾上腺肿瘤患者的脆弱性骨折的患病率和出现，以及将建立MAC在脆弱性上的严重性。 AIM 2中提出的实验将确定在MAC患者中观察到的异常立体声代谢组是否与受损有关骨密度，质量，结构和代谢，这反过椎骨和非椎骨骨折。 AIM 3中提出的实验将确定异常是否 MAC患者中皮质醇分泌的昼夜节律模式与异常代谢有关和骨转换标记的改变。拟议的职业发展奖和相关候选人培训解决了重要的健康 MAC患者的骨骼健康问题，并为候选人做好独立职业的准备研究，实现NIH指导的以患者为导向的研究职业发展奖的目标（父k23-不允许独立临床试验），PA-18-375。卓越的资源和机构梅奥诊所的支持，杰出的多学科心态团队，并提出了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，并且全国认可的类固醇对骨骼健康和设计干预措施有效的专家改善肾上腺肿瘤患者的骨骼健康。

项目成果

期刊论文数量（32）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Classic and 11-oxygenated androgens in serum and saliva across adulthood: a cross-sectional study analyzing the impact of age, body mass index, and diurnal and menstrual cycle variation.

成年期血清和唾液中的经典雄激素和 11 氧化雄激素：一项横断面研究，分析年龄、体重指数以及昼夜和月经周期变化的影响。

DOI：
10.1093/ejendo/lvac017
发表时间：
2023
期刊：
European journal of endocrinology
影响因子：
5.8
作者：
Schiffer L
通讯作者：
Schiffer L

The Impact of the COVID-19 Pandemic on Self-Reported Outcomes in Patients With Adrenal Insufficiency.

DOI：
10.1210/clinem/dgab334
发表时间：
2021-06-16
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
0
作者：
Li D;Suresh M;Abbondanza T;Vaidya A;Bancos I
通讯作者：
Bancos I

Adrenal insufficiency.

DOI：
10.1016/s0140-6736(00)42306-8
发表时间：
1997
期刊：
Current therapy in endocrinology and metabolism
影响因子：
0
作者：
通讯作者：

Diagnostic Accuracy of Dehydroepiandrosterone Sulfate and Corticotropin in Autonomous Cortisol Secretion.

DOI：
10.3390/biomedicines9070741
发表时间：
2021-06-28
期刊：
Biomedicines
影响因子：
4.7
作者：
Carafone LE;Zhang CD;Li D;Lazik N;Hamidi O;Hurtado MD;Young WF Jr;Thomas MA;Dy BM;Lyden ML;Foster TR;McKenzie TJ;Bancos I
通讯作者：
Bancos I

Pheochromocytoma and Paraganglioma in Pregnancy: a New Era.