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: 8202110
• 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/8202110
• 关键词: Address; Adrenal Glands; Adrenal gland hypofunction; Adult; Affect; Afghanistan; Age; Alcohol consumption; American; Anxiety; Behavioral; Behavioral Symptoms; Blast Cell; Body Composition; Body mass index; Brain Concussion; Brain Injuries; Cardiovascular Diseases; Cessation of life; Characteristics; Cholesterol; Chronic; Clinical Treatment; Cognitive; Coma; Conflict (Psychology); Consumption; Control Groups; Corticotropin; Craniocerebral Trauma; Data; Defect; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Equipment and supply inventories; Etiology; Exhibits; Family Relationship; Fatigue; Fatty acid glycerol esters; Freedom; Frequencies; Functional disorder; Glucagon; Goals; Gold; Health; Hormones; Hyperlipidemia; Hypertension; Hypopituitarism; Impaired cognition; Impairment; Incidence; Inflammation; Injury; Insulin-Like Growth Factor I; Investigation; Iraq; Learning; Libido; Lipids; Low Prevalence; Low-Density Lipoproteins; Measurement; Measures; Medical; Memory; Memory impairment; Mental Depression; Mild Concussions; Moods; Muscle; Nature; Obesity; Occupations; Outcome; Paralysed; Patients; Performance; Physiological; Pituitary Gland; Pituitary Hormones; Plasma; Population; Post-Traumatic Stress Disorders; Prevalence; Procedures; Production; Published Comment; Quality of life; Quality-of-Life Assessment; Questionnaires; Recovery; Rehabilitation therapy; Relative (related person); Reporting; Risk; Screening procedure; Selection Criteria; Serum; Services; Severities; Sleep; Sleep Disorders; Sleep disturbances; Sleeplessness; Social isolation; Soldier; Supervision; Symptoms; Syndrome; Test Result; Testing; Therapeutic Intervention; Time; Trauma; Traumatic Brain Injury; Verbal Learning; Veterans; alcohol use disorder; base; behavior test; cognitive function; cost; cost effective; depressive symptoms; disability; effective therapy; experience; growth hormone deficiency; high risk; improved; indexing; insulin tolerance; member; muscle form; neurobehavioral; neurocognitive test; operation; premature; prevent; research clinical testing; response

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）： 爆炸装置爆炸效应造成的轻度创伤性脑损伤 (mTBI) 是当前伊拉克和阿富汗冲突的“标志性损伤”，影响了大约 18% 的部署美国军人。尽管与导致死亡、昏迷或瘫痪的脑损伤相比，mTBI 被称为“轻度”，但 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）可能会造成毁灭性的个人、职业和家庭后果。记忆力和注意力受损、焦虑、烦躁和情绪不稳定增加以及睡眠障碍会干扰工作和家庭关系，造成严重残疾。对于各种原因造成的平民 TBI 病例，垂体功能低下筛查已越来越被认为是 TBI 长期结果调查的必要组成部分。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，30-70% 的 TBI 病例在受伤后至少一年内发生，且其发生与创伤严重程度无关。垂体功能减退症与许多非特异性症状相关，这些症状很容易被误认为是创伤后应激障碍 (PTSD) 和慢性脑震荡后综合症的行为症状，包括疲劳、焦虑、抑郁、烦躁、失眠和生活质量下降 (QoL) 以及变化身体成分，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，大多数情况下这些症状可以通过激素替代疗法成功缓解。垂体激素及其目标激素基线浓度的测量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，生长激素缺乏症 (GHD) 和继发性肾上腺皮质功能不全 (sAI) 的明确诊断通常需要使用激发试验。激发试验成本高、耗时且费力。 此外，胰岛素耐量试验（ITT）通常被认为是 GHD 和 sAI 的金标准测试，需要严密的医疗监督，并且在头部受伤的情况下是禁忌的，因此不能用于诊断 OIF 的 GHD 或 sAI /OEF 患有 mTBI 的退伍军人。这项研究的基本原理是基于平民环境中与 TBI 相关的垂体功能低下的高风险，显然缺乏对 OIF/OEF 服役人员或退伍军人中爆炸 mTBI 后垂体功能障碍的任何系统调查，并且缺乏垂体功能低下的常规筛查在这个人群中。我们建议调查 OIF/OEF 退伍军人中与急变 mTBI 相关的垂体功能减退症的频率和具体性质，并设计一种可靠、具有成本效益且高效的筛查程序，以指导适当的治疗干预、促进康复和康复并提高生活质量。该研究的目的是： 1) 确定从基础激素测量结果中容易识别的垂体激素缺陷在患有爆炸 mTBI 的 OIF/OEF 退伍军人中是否比未遭受爆炸创伤的部署对照受试者更普遍； 2) 确定胰高血糖素刺激试验 (GST) 是否可以替代（禁忌的）ITT，作为诊断患有爆炸暴露 mTBI 的 OIF/OEF 退伍军人中的 GHD 和/或 sAI 的激发试验； 3) 确定垂体机能减退的证据是否与睡眠问题频率增加、慢性脑震荡后综合征症状、抑郁和创伤后应激障碍、认知能力较低、身体成分不良变化和较差的生活质量相关； 4) 确定与更昂贵和耗时的刺激相比，基础激素测量、血脂谱、身体成分指数以及其他人口统计、行为和症状值的组合是否可以以可接受的准确性用于诊断 GHD 和 sAI测试程序。