Pituitary dysfunction, behavioral symptoms, and quality of life after blast mTBI

脑垂体功能障碍、行为症状和冲击波 mTBI 后的生活质量

• 批准号: 8838165
• 负责人: Charles W. Wilkinson
• 金额: --
• 依托单位: VA PUGET SOUND HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8838165
• 关键词: Adrenal gland hypofunction; Affect; Afghanistan; American; Anxiety; Behavioral Symptoms; Blast Cell; Body Composition; Brain Injuries; Cardiovascular Diseases; Cessation of life; Characteristics; Cholesterol; Chronic; Clinical Treatment; Cognitive; Coma; Conflict (Psychology); Craniocerebral Trauma; Defect; Development; Devices; Diagnosis; Diagnostic; Family Relationship; Fatigue; Fatty acid glycerol esters; Freedom; Frequencies; Functional disorder; Glucagon; Gold; Hormones; Hyperlipidemia; Hypertension; Hypopituitarism; Impairment; Inflammation; Injury; Investigation; Iraq; Learning; Libido; Lipids; Low-Density Lipoproteins; Measurement; Measures; Medical; Memory; Memory impairment; Mental Depression; Mild Concussions; Moods; Muscle; Nature; Obesity; Occupations; Outcome; Paralysed; Performance; Pituitary Gland; Pituitary Hormones; Population; Post-Traumatic Stress Disorders; Procedures; Production; Published Comment; Quality of life; Recovery; Rehabilitation therapy; Reporting; Screening procedure; Serum; Services; Severities; Sleep Disorders; Sleep disturbances; Sleeplessness; Social isolation; Soldier; Supervision; Symptoms; Syndrome; Testing; Therapeutic Intervention; Time; Trauma; Traumatic Brain Injury; Veterans; base; cost effective; disability; growth hormone deficiency; high risk; improved; indexing; insulin tolerance; member; muscle form; operation; premature; prevent; research clinical testing; screening

DESCRIPTION (provided by applicant): Mild traumatic brain injury (mTBI) caused by blast effects of explosive devices is the "signature injury" of the current Iraq and Afghanistan conflicts, affecting an estimated 18% of deployed American service members. Although termed "mild" in comparison to brain injuries resulting in death, coma, or paralysis, mTBI, particularly repetitive mTBI characteristic of soldiers deployed to Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF), in Afghanistan, may have devastating personal, professional and domestic consequences. Impairment of memory and concentration, increased anxiety, irritability and mood instability, and sleep disturbance interfere with job and family relationships, producing substantial disability. In cases of civilian TBI from all causes, screening for hypopituitarism has been increasingly recognized as a necessary component in the investigation of the long-term outcome of TBI. Hypopituitarism, as defined by deficient production of one or more pituitary hormones measured at least one year after injury, has been reported to occur in 30-70% of TBI cases, and its occurrence is not related to trauma severity. Hypopituitarism is associated with numerous non-specific symptoms easily mistaken for behavioral symptoms of posttraumatic stress disorder (PTSD) and chronic postconcussive syndrome, including fatigue, anxiety, depression, irritability, insomnia, and decreased quality of life (QoL), as well as changes in body composition including increased fat percentage, hyperlipidemia, and a decrease in muscle mass. If accurately diagnosed as a consequence of hypopituitarism, these symptoms can in most cases be successfully relieved with hormone replacement. Measurement of baseline concentrations of pituitary hormones and their target hormones has been shown to have considerable diagnostic utility in identifying most types of pituitary deficiencies. However, definitive diagnosis of growth hormone deficiency (GHD) and secondary adrenal insufficiency (sAI) typically requires the use of provocative testing. Provocative testing is costly, time-consuming, and laborintensive. In addition, the insulin tolerance test (ITT), which is generally considered the gold standard test for both GHD and sAI, requires intensive medical supervision and is contraindicated in cases of head injury, so it cannot be employed to diagnose GHD or sAI in OIF/OEF Veterans with mTBI. The rationale for this study is based on the high risk for hypopituitarism associated with TBI in civilian settings, the apparent absence of any systematic investigation of pituitary dysfunction after blast mTBI in OIF/OEF service members or Veterans, and the absence of routine screening for hypopituitarism in this population. We propose to investigate the frequency and specific nature of blast mTBI-related hypopituitarism in OIF/OEF Veterans and to devise a reliable, cost-effective, and efficient screening procedure that will direct appropriate therapeutic intervention, facilitate recovery and rehabilitation, and improve QoL. The objectives of the study are: 1) to determine whether pituitary hormone defects that are readily identifiable from the results of basal hormone measurements are more prevalent in OIF/OEF Veterans with blast mTBI than in deployment control subjects not exposed to blast trauma; 2) to determine whether the glucagon stimulation test (GST) can substitute for the (contraindicated) ITT as a provocative test for diagnosing GHD and/or sAI in OIF/OEF Veterans with blast exposure mTBI; 3) to determine whether evidence of hypopituitarism is associated with increased frequency of sleep problems, symptoms of chronic postconcussive syndrome, depression, and PTSD, lower cognitive performance, adverse changes in body composition, and poorer QoL; and 4) to determine whether a combination of basal hormone measures, serum lipid profiles, body composition indices, and additional demographic, behavioral, and symptom values can be used to diagnose GHD and sAI with acceptable accuracy compared to more expensive and time-consuming provocative testing procedures.

描述（由申请人提供）： 爆炸装置爆炸效应引起的轻度创伤性脑损伤（mTBI）是“标志性损伤” 目前的伊拉克和阿富汗冲突，影响了大约 18% 的美国部署部队 成员。尽管与导致死亡、昏迷或瘫痪的脑损伤相比被称为“轻度”， mTBI，特别是部署到伊拉克自由行动 (OIF) 的士兵的重复性 mTBI 特征 阿富汗的持久自由行动（OEF）可能会对个人、职业造成毁灭性的影响 和国内后果。记忆力和注意力受损、焦虑、易怒加剧 情绪不稳定、睡眠障碍会干扰工作和家庭关系，产生 严重残疾。对于各种原因造成的平民 TBI 病例，已进行垂体功能低下筛查 越来越多地被认为是调查长期结果的必要组成部分 创伤性脑损伤。垂体功能减退症，定义为一种或多种垂体激素产生不足 据报道，在受伤后至少一年内，30-70% 的 TBI 病例会发生这种情况，而且这种情况的发生率并不高。 与创伤严重程度有关。垂体功能减退症很容易与许多非特异性症状相关 被误认为是创伤后应激障碍 (PTSD) 和慢性脑震荡后的行为症状 综合症，包括疲劳、焦虑、抑郁、烦躁、失眠和生活质量下降 (QoL)，以及身体成分的变化，包括脂肪百分比增加、高脂血症和 肌肉质量减少。如果准确诊断为垂体功能减退症的结果，这些 在大多数情况下，通过激素替代疗法可以成功缓解症状。测量 垂体激素及其目标激素的基线浓度已被证明 在识别大多数类型的垂体缺陷方面具有相当大的诊断效用。然而，确定的 通常诊断生长激素缺乏症 (GHD) 和继发性肾上腺皮质功能不全 (SAI) 需要使用激发试验。激发试验成本高、耗时且费力。 此外，通常被认为是金标准的胰岛素耐量测试（ITT） GHD 和 sAI 检测，需要严格的医疗监督，并且在以下情况下是禁忌的 头部损伤，因此不能用于诊断患有 mTBI 的 OIF/OEF 退伍军人的 GHD 或 sAI。这 这项研究的理由是基于平民中与 TBI 相关的垂体功能减退症的高风险 环境中，明显缺乏对爆炸 mTBI 后垂体功能障碍的任何系统研究 OIF/OEF 服役人员或退伍军人中，以及缺乏垂体功能低下的常规筛查 这个人口。我们建议调查 mTBI 相关爆炸的频率和具体性质 OIF/OEF 退伍军人的垂体功能减退症，并设计一种可靠、具有成本效益且高效的筛查方法 指导适当治疗干预、促进康复和康复的程序，以及 提高生活质量。该研究的目的是：1）确定垂体激素缺陷是否会导致 很容易从基础激素测量结果中识别出来 在 OIF/OEF 中更为普遍 遭受爆炸 mTBI 的退伍军人与未遭受爆炸创伤的部署对照受试者相比； 2）到 确定胰高血糖素刺激试验 (GST) 是否可以替代（禁忌的）ITT 作为 用于诊断患有爆炸暴露 mTBI 的 OIF/OEF 退伍军人的 GHD 和/或 SAI 的激发试验； 3）到 确定垂体机能减退的证据是否与睡眠频率增加有关 慢性脑震荡后综合症、抑郁症和创伤后应激障碍 (PTSD) 的问题、症状、认知能力较低 表现、身体成分的不利变化和较差的生活质量； 4) 确定是否 基础激素测量、血脂谱、身体成分指数等的组合 人口统计学、行为和症状值可用于诊断 GHD 和 sAI，且可接受 与更昂贵且耗时的激发测试程序相比，其准确性更高。