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症影响0.2%至0.5%的人口，新增约10万人 美国每年都有病例。女性的发病率是男性的三倍，而且发病率随着年龄的增长而增加，因此据估计，高达2%的绝经后女性患有这种疾病。相关的发病率和后遗症包括骨密度降低、骨折和肾结石。 目前，对原发性甲状旁腺功能亢进症的危险因素知之甚少。我们建议 前瞻性地研究饮食、激素和生活方式危险因素与原发性甲状旁腺功能亢进症的发展之间的关系，在两项正在进行的大型女性队列研究中：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机能亢进症的甲状旁腺腺瘤是单克隆性的，提示这些肿瘤起源于具有生长相关突变的单个细胞。因此，导致甲状旁腺增生的因素可能会增加发展为原发性甲状旁腺功能亢进症的风险。具体目标如下： 目的1)节食。我们假设较低的钙摄入量、较高的磷摄入量和较低的 镁摄入量独立地与发展为原发性甲状旁腺功能亢进症的高风险相关。 目的2)绝经状况和绝经后激素使用情况。原发疾病的发病率 甲状旁腺机能亢进症在绝经后急剧增加。我们假设更年期是独立的 与患原发性甲状旁腺机能亢进症的风险较高有关，而绝经后使用激素与患原发性甲状旁腺机能亢进症的风险较低有关。 目的3)生活方式因素。我们假设较高的身体质量指数，较低的估计值25- 羟基维生素D水平和较高的酒精摄入量与发展为原发性甲状旁腺功能亢进症的风险有关。 我们前瞻性队列研究的结果将是原发性甲状旁腺功能亢进症的发生率， 所有病例均经医学复核确认。因为我们预计会有1200多个病例，统计数字 电力将会很强。例如，检测五分位数钙的危险比为1.4的功率为0.98。 这项研究代表了第一次大规模的前瞻性努力，以确定可修改的风险因素 原发性甲状旁腺功能亢进症。这项研究的发现可能会对预防疾病发展及其相关后遗症产生重要的公共卫生影响。最后，这一庞大的原发性甲状旁腺功能亢进症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.