Dietary, Hormonal, and Lifestyle Factors and Risk of Primary Hyperparathyroidism

描述（由申请人提供）： 原发性甲状旁腺功能亢进影响0.2%至0.5%的人口，约有100，000例新发 每年在美国的案件。女性的患病率是男性的三倍，发病率随着年龄的增长而增加，因此估计高达2%的绝经后妇女患有这种疾病。相关的发病率和后遗症包括骨矿物质密度降低、骨折和肾结石。 目前，对原发性甲状旁腺功能亢进的危险因素知之甚少。我们建议 前瞻性研究了饮食、激素和生活方式危险因素与原发性甲状旁腺功能亢进症发生之间的关系，两项大型的、正在进行的女性队列研究：护士健康研究I（N= 85，061）和II（N= 75，815）。散发性原发性甲状旁腺功能亢进的甲状旁腺腺瘤是单克隆的，这表明这些肿瘤起源于具有生长基因突变的单细胞。因此，导致甲状旁腺增生的因素可能会增加原发性甲状旁腺功能亢进的风险。具体目标如下： 目标1）饮食。我们假设，低钙摄入量，高磷摄入量， 镁的摄入量与原发性甲状旁腺功能亢进的高风险独立相关。 目的2）月经状态和月经后激素的使用。原发性肝癌的发病率 绝经后甲状旁腺功能亢进急剧上升。我们假设更年期是独立于 与原发性甲状旁腺功能亢进的高风险相关，绝经后使用激素与原发性甲状旁腺功能亢进的低风险相关。 目标3）生活方式因素。我们假设体重指数越高，估计的25- 羟维生素D水平和较高的饮酒量与发生原发性甲状旁腺功能亢进的风险有关。 我们的前瞻性队列研究的结果将是原发性甲状旁腺功能亢进的发生率， 所有病例均经医学检查确认。因为我们预计会有超过1200例， 力量会很高。例如，检测钙五分位数风险比为1.4的功效为0.98。 这项研究代表了第一次大规模的前瞻性努力，以确定可改变的风险因素， 原发性甲状旁腺功能亢进这项研究的发现可能通过预防疾病发展及其相关后遗症而对公共卫生产生重要影响。最后，这个大型的原发性甲状旁腺功能亢进病例队列的建立将为未来的研究提供宝贵的资源。

DESCRIPTION (provided by applicant): Primary hyperparathyroidism affects 0.2% to 0.5% of the population, with approximately 100,000 new cases in the U.S. each year. Women are three times more commonly affected than men and the incidence increases with age, so that up to 2% of post-menopausal women are estimated to have this disease. Associated morbidity and sequelae include decreased bone mineral density, fractures, and kidney stones. Currently, little is known about risk factors for developing primary hyperparathyroidism. We propose to study prospectively the relations between dietary, hormonal, and lifestyle risk factors and the development of primary hyperparathyroidism in two large, ongoing cohort studies of women: the Nurses Health Studies I (N=85,061) and II (N=75,815). The parathyroid adenomas of sporadic primary hyperparathyroidism are monoclonal, suggesting that these neoplasms originate from single cells with a growth conferring mutation. Factors that cause parathyroid hyperplasia therefore may increase the risk for developing primary hyperparathyroidism. The specific aims are the following: Aim 1) Diet. We hypothesize that lower calcium intake, higher phosphorous intake, and lower magnesium intake are independently associated with higher risk of developing primary hyperparathyroidism. Aim 2) Menopausal Status and Post-Menopausal Hormone Use. The incidence of primary hyperparathyroidism rises sharply after menopause. We hypothesize that menopause is independently associated with a higher risk of developing primary hyperparathyroidism and that post-menopausal hormone use is associated with a lower risk of developing primary hyperparathyroidism. Aim 3) Lifestyle Factors. We hypothesize that higher body mass index, lower estimated 25- hydroxyvitamin D levels, and higher alcohol consumption are associated with the risk of developing primary hyperparathyroidism. The outcome of our prospective cohort studies will be the incidence of primary hyperparathyroidism, with all cases confirmed by medical review. Because we expect to have over 1200 cases, the statistical power will be high. For example, the power to detect a hazard ratio of 1.4 across quintiles of calcium is 0.98. This study represents the first large-scale prospective effort to identify modifiable risk factors for primary hyperparathyroidism. Findings from this study could have important public health implications by preventing disease development and its associated sequelae. Finally, the creation of this large cohort of primary hyperparathyroidism cases will serve as a valuable resource for future research.