ACUTE AND CHRONIC HYPOPITUITARISM AFTER ANEURYSMAL SUBARACHNOID HEMORRHAGE

动脉瘤性蛛网膜下腔出血后的急性和慢性垂体功能减退症

• 批准号: 7376082
• 负责人: DANIEL Fain KELLY
• 金额: $ 1.24万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376082
• 关键词: ACUTE; CHRONIC; HYPOPITUITARISM; AFTER; ANEURYSMAL

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. Currently, pituitary hormone function is rarely considered in the care of patients with bleeding into or over the surface of the brain as the result of a ruptured blood vessel (aneurysm). This type of brain bleeding is called aneurysmal subarachnoid hemorrhage (SAH). Yet, aneurysmal SAH poses risk to hormonal function controlled by the pituitary gland (a structure at the base of the brain and connected to the brain by blood vessels) given its delicate blood supply and connections to the brain that are sensitive to a variety of insults including the initial aneurysm bleeding, narrowing of blood vessels as a result of the bleeding (cerebral vasospasm), increased cerebrospinal fluid in the brain (hydrocephalus) and increased pressure in the brain. It is the primary hypothesis of this study that many SAH patients suffer from unrecognized pituitary hormone loss that acutely and chronically worsens the effects of the initial brain bleeding and may prevent maximal recovery of brain function. The major hypotheses being tested in this study are that i) pituitary hormonal loss after SAH results primarily from an inadequate blood supply to the pituitary gland and/or its connections to the brain; ii) that SAH can result in a lack of stress hormone (cortisol) production (acute secondary adrenal insufficiency), iii) that SAH-induced low growth hormone worsens vasospasm after SAH and iv) that SAH can cause chronic loss of pituitary hormone production (hypopituitarism). These hypotheses will be tested in a two-part pilot study of two aneurysmal SAH patient groups (Acute SAH Cohort and Chronic SAH Cohort) at UCLA and Harbor-UCLA Medical Centers. The results of this pilot project will be used as preliminary data for a more comprehensive NIH grant application addressing SAH-induced pituitary hormonal loss and its treatment. Acute SAH: During the first 14 days after SAH, patients (while in the ICU only) will undergo daily hormonal blood draws to assess for cortisol and growth hormone dysfunction, sodium levels and proteins that cause inflammation (cytokines). Daily studies {transcranial Doppler (TCD)} will be performed to document development of cerebral vasospasm. The frequency of acute cortisol and growth hormone insufficiency and the risk factors associated with the development of these acute hormonal insufficiencies will be determined. If patients have a catheter in place to measure the pressure in the brain (ventriculostomy), samples of cerebrospinal fluid (fluid in the brain) will be collected to measure growth hormone and proteins that cause inflammation. Patients with low cortisol levels (< 5 ug/dL) will be treated with a similar stress hormone (hydrocortisone). The role of growth hormone loss in the development of vasospasm will also be studied. On hospital day 6, the patient will also have a stimulation study using growth hormone releasing hormone (GHRH) and arginine (an amino acid) to further assess for growth hormone loss. Chronic Hypopituitarism after SAH: Aneurysmal SAH patients who suffered a SAH 6 to 12 months prior, will undergo i) pituitary hormone stimulation testing to assess for pituitary failure and ii) neurobehavioral testing and quality of life assessment (tests for memory, concentration, attention, depression, anxiety and fatigue). All patients diagnosed with pituitary hormonal loss will be referred to an endocrinologist. Those diagnosed with low cortisol or low thyroid will be treated by replacement of these essential hormones. Men diagnosed with low testosterone (male sex hormone) and women who have not gone through menopause, diagnosed with low estrogen (female sex hormone), will be recommended to start replacement therapy of these hormones. Patients with low growth hormone will be offered GH-replacement therapy. The results of the neurobehavioral and quality of life tests will be correlated with the rate of hormonal insufficiencies. Patients will be consented separately for the Acute and the Chronic Phases of the study. If patients are unable to consent because of an altered mental state, proxy consent will be obtained from the legal guardian or next of kin. If the patient becomes able to be consented during the acute phase (i.e., the blood draws in the first 14 days after the SAH), consent will be obtained from the patient. The benefit of the study for individual patients is that they may be diagnosed with a treatable hormonal loss that would otherwise have gone undetected had they not participated in the study. Given that the acute and chronic studies only involve well-established hormonal testing and blood draws, the potential benefits of study participation outweigh the risks.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。目前，由于血管破裂（动脉瘤），垂体激素功能很少被考虑在大脑表面或大脑表面出血的患者中。这种类型的脑出血称为动脉瘤性蛛网膜下腔出血（SAH）。然而，鉴于其微妙的血液供应和与大脑的联系，对垂体（大脑底部的结构并与大脑相连）控制的激素功能构成了风险大脑（脑积水）和大脑压力增加。这项研究的主要假设是，许多SAH患者遭受了未识别的垂体激素丧失，从而急性和慢性使最初脑出血的影响恶化，并可能阻止大脑功能的最大恢复。在这项研究中测试的主要假设是，i）SAH后SAH后主要是由于血液供应不足而导致的垂体激素损失和/或其与大脑的连接； ii）SAH可能导致缺乏应激激素（皮质醇）的产生（急性继发性肾上腺功能不全），iii）SAH诱导的低生长激素会使SAH和IV后SAH后的血管痉挛恶化，SAH会导致垂体激素的慢性丧失垂体激素的丧失（低载体症）。这些假设将在UCLA和Harbour-UCLA医疗中心的两个动脉瘤SAH患者组（急性SAH队列和慢性SAH队列）的两部分试点研究中进行检验。该试点项目的结果将用作更全面的NIH赠款申请，以解决SAH诱导的垂体激素损失及其治疗。 急性SAH：在SAH后的头14天内，患者（仅在ICU中）将接受每日荷尔蒙血液抽血，以评估导致炎症（细胞因子）的皮质醇和生长激素功能障碍，钠水平和蛋白质。每日研究{经颅多普勒（TCD）}将进行记录脑血管痉挛的发育。将确定急性皮质醇和生长激素功能不全的频率以及与这些急性激素不足相关的风险因素。如果患者具有适当的测量大脑压力（心室切开术），则将收集脑脊液（大脑中的液体）样品，以测量引起炎症的生长激素和蛋白质。皮质醇水平低（<5 ug/dL）的患者将用类似的应激激素（氢化可的松）治疗。还将研究生长激素丧失在血管痉挛发展中的作用。在医院第6天，患者还将使用生长激素释放激素（GHRH）和精氨酸（氨基酸）进行刺激研究，以进一步评估生长激素损失。 SAH之后的慢性低血源性：遭受SAH 6至12个月前的动脉瘤SAH患者，将接受i）垂体激素刺激测试，以评估垂体失败和iii）ii ii）神经行为测试和神经性生活质量评估（记忆，注意力，注意力，注意力，注意力，注意力，注意力，抑郁，焦虑，焦虑，焦虑，焦虑，焦虑和疲劳）。所有被诊断为垂体激素损失的患者都将转介给内分泌学家。诊断为低皮质醇或低甲状腺的人将通过替代这些必需激素来治疗。被诊断出睾丸激素低的男性和未经历被诊断为低雌激素（女性性激素）的更年期的女性，建议开始替代这些激素的疗法。低生长激素的患者将提供GH-替代疗法。神经行为和生活质量测试的结果将与激素不足的速度相关。该研究的急性和慢性阶段将分别同意。如果患者由于精神状态而无法同意，将从法定监护人或近亲获得代理同意。如果患者能够在急性阶段同意（即，在SAH之后的头14天中抽血），将从患者那里获得同意。该研究对个别患者的好处是，他们可能会被诊断出患有可治疗的激素损失，如果他们不参加研究，否则他们将无法被发现。鉴于急性和慢性研究仅涉及良好的荷尔蒙测试和血液抽血，因此研究参与的潜在益处大于风险。