HORMONE CONCENTRATIONS TO ASSESS ADRENAL FUNCTION IN CRITICALLY ILL PATIENTS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。应激事件中脑下垂体肾上腺功能的激活是一种主要的生理防御机制，其特征是促肾上腺皮质激素(ACTH)的产生增加和糖皮质激素的分泌增加。目前使用的评估肾上腺功能完整性的方法依赖于血清皮质醇的测定。由于循环中皮质醇与蛋白质的高度结合，其血清浓度会随着这些结合蛋白的变化而变化。最近的一项研究表明，血清游离皮质醇水平是糖皮质激素分泌的更好标记物。本研究将探讨测定唾液皮质醇浓度作为危重成人患者血清游离皮质醇水平标志物的价值。它还将研究测量肾上腺皮质激素依赖性雄激素(脱氢表雄酮/脱氢表雄酮-S)作为该人群肾上腺功能标志物的价值。假设唾液皮质醇浓度与血清游离皮质醇水平密切相关，这种测量将是危重患者糖皮质激素分泌的可靠和实用的替代指标。这对患有低蛋白血症的患者尤其重要，因为测得的血清总水平可能低得令人误解。这项研究将招募38名成年男性和女性进入重症监护病房，以及19名年龄和性别分布相似的健康志愿者(共57名受试者)。受试者将接受内分泌团队的临床评估，以确定研究的资格。受试者将接受一项标准的Cortrosyn刺激测试，包括采集血液和唾液。对于所有正常的志愿者，这项测试将在GCRC的门诊就诊中进行。内分泌团队将为参与研究的所有患者提供书面临床评估，包括与每个患者的内分泌临床评估相关的诊断和治疗建议。从该方案获得的数据将作为一项更大规模的多中心研究的先导性研究，评估这些方法以确定疾病特异性肾上腺反应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Activation of the pituitary adrenal function during stressful events is a major physiological defense mechanism marked by elevated adrenocorticotropic hormone (ACTH) production and increased glucocorticoid secretion. Currently used measures to assess the integrity of the adrenal function rely on serum cortisol determinations. With the high degree of protein binding for cortisol in the circulation, its serum concentration is changed with alterations in these binding proteins. A recent study demonstrated that serum free cortisol levels are better markers for glucocorticoid secretion. This study will investigate the value of measuring salivary cortisol concentration as a marker for serum free cortisol level in critically ill adult patients. It will also study the value of measuring ACTH-dependent adrenal androgens (DHEA/DHEA-S) as markers for adrenal function in this population. The hypothesis is that salivary cortisol concentration strongly correlates with the serum free cortisol level and that such measurements would be a reliable and practical surrogate for glucocorticoid secretion in critically ill patients. This would be particularly important in patients with hypoproteinemia where measured total serum levels can be misleadingly low. The study will enroll 38 adult men and women in the intensive care unit and 19 healthy volunteers of similar age and gender distribution (a total of 57 subjects). Subjects will have a clinical assessment by the endocrine team to determine eligibility for study. Subjects will have one standard cortrosyn stimulation test involving blood and saliva collection. For all normal volunteers, this test will be conducted in an outpatient visit at the GCRC. The endocrine team will provide a written clinical evaluation of all patients involved in the study, including diagnostic and therapeutic recommendations pertinent to each patient's endocrine clinical assessment. The data obtained from this protocol will serve as a pilot study for a larger multi-center investigation evaluating these measures to define illness-specific adrenal responses.