Hypopituitarism after Moderate and Severe Head Injury

中度和重度头部受伤后的垂体功能减退症

• 批准号: 6872940
• 负责人: DANIEL Fain KELLY
• 金额: $ 50.94万
• 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: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6872940
• 关键词: acute disease /disorder; behavior test; behavioral /social science research tag; bioimaging /biomedical imaging; brain imaging /visualization /scanning; brain injury; chronic disease /disorder; clinical trials; cortisol; hormone therapy; human subject; human therapy evaluation; hypoadrenalism; hypopituitarism; hypothalamus; longitudinal human study; magnetic resonance imaging; neuroendocrine system; neuropsychological tests; neuropsychology; patient oriented research; pituitary disorder diagnosis; pituitary dwarfism; quality of life; somatotropin

DESCRIPTION: (Verbatim from applicant's abstract) Pituitary function is rarely considered in the care of patients with traumatic brain injury (TBI). Yet, TBI poses significant risk to pituitary function given the gland's encasement within the sella, its delicate infundibular-hypothalamic structures and vulnerable vascular supply. Autopsy studies of fatal head injury victims confirm that up to one third sustain pituitary necrosis and hundreds of case reports document chronic post-traumatic pituitary failure. The long-term neurobehavioral problems that plague a majority of TBI victims are quite similar to those of patients with hypopituitarism. It is the primary hypothesis of this study that many TBI victims suffer from unrecognized pituitary dysfunction that acutely and chronically compounds the initial brain injury and limits maximal recovery. The major hypotheses being tested in this study are that i) post-traumatic pituitary failure, both acute and chronic, results primarily from a vascular insult to the pituitary gland and/or its hypothalamic-infundibular connections; ii) in the acute phase of TBI such injury can result in acute secondary adrenal insufficiency, iii) in the chronic phase of TBI such injury can result in long-term hypopituitarism, and iv) treatment of pituitary hormone deficiencies will improve neurobehavioral functioning and quality of life in the chronic post-traumatic state. These hypotheses will be tested in a three-phase study. In the first phase, acutely post-injury, subjects will undergo serial determinations of adrenocortical function to diagnose and treat acute adrenal insufficiency. Patients found to have inappropriately low cortisol levels, will be randomized to placebo or hydrocortisone therapy for 48 hours, and changes in blood pressure and vasopressor requirements will be monitored. Pituitary/hypothalamic MRIs will also be performed at 10 days and 6 months post-injury to assess for acute structural lesions and chronic pituitary volumetric changes. In the second phase, at 2 and 6 months post-injury, pituitary function tests will be performed. Hormone deficient patients will be placed on hormone replacement except for growth hormone (GH) after the 2-month time point. In the third phase, from 6 to 12 months post-injury, TBI patients with GH deficiency or GH insufficiency, who have memory impairment, concentration deficits, depression, anxiety or fatigue will be entered into a double-blind placebo-controlled GH replacement therapy trial to assess changes in these neurobehavioral and quality of life complaints. By diagnosing and treating both acute and chronic traumatic neuroendocrine deficiencies, this study may dramatically improve the lone-term prognosis of many TBI patients.

描述：（逐字化的申请人摘要）垂体功能很少 考虑到脑损伤（TBI）患者的护理。但是，TBI 鉴于腺体的包裹，对垂体功能构成了重大风险 在塞拉内部，其微妙的漏斗性 - 高层丘脑结构和 脆弱的血管供应。致命的头部受害者的尸检研究 确认多达三分之一的维持垂体坏死和数百例病例 报告文件慢性创伤后垂体失败。长期 困扰大多数TBI受害者的神经行为问题是 类似于降尿症患者的患者。这是主要假设 在这项研究中，许多TBI受害者都遭受了未知的垂体 急性和慢性的功能障碍会使最初的脑损伤和 限制最大恢复。在这项研究中检验的主要假设是 i）创伤后垂体失败，急性和慢性结果 主要从血管侮辱到垂体和/或它 下丘脑 - 内颌骨连接； ii）在TBI的急性阶段 受伤会导致急性继发性肾上腺功能不全，iii） TBI的阶段这种伤害会导致长期缺血性，而IV） 垂体激素缺乏症的治疗将改善神经行为 慢性创伤后状态的功能和生活质量。这些 假设将在三相研究中进行检验。在第一阶段，敏锐 伤害后，受试者将接受肾上腺皮质的串行确定 诊断和治疗急性肾上腺功能不全的功能。发现患者 皮质醇水平不当，将随机分为安慰剂或 氢化可的松治疗48小时，血压的变化和 血管加压器的要求将受到监视。垂体/下丘脑MRIS 也应在伤害后10天和6个月进行急性评估 结构性病变和慢性垂体体积变化。在第二个 阶段，在伤害后2和6个月，垂体功能测试将是 执行。激素缺乏患者将被置于激素替代 除了2个月后生长激素（GH）外。在第三 阶段，受伤后6至12个月，TBI患有GH缺乏症或GH的患者 不足，有记忆力障碍，浓度缺陷，抑郁症， 焦虑或疲劳将进入双盲安慰剂对照的GH 替代疗法试验，以评估这些神经行为的变化和 生活质量投诉。通过诊断和治疗急性和慢性 创伤性神经内分泌缺乏症，这项研究可能会大大改善 许多TBI患者的唯一预后。