CONSEQUENCES OF HYPOPITUITARISM FOLLOWING TRAUMATIC BRAIN INJURY (TBI)

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。假设：本方案将探讨创伤性脑损伤（TBI）相关垂体功能减退对身体组成、生活质量（QOL）和日常生活活动（ADL）的影响。我们假设：1。TBI与高度垂体功能低下相关，包括生长激素缺乏。2. 与垂体功能正常的患者相比，TBI患者的垂体功能低下与骨骼肌量减少、体脂增加、生活质量下降和ADL能力下降有关。3. 在有TBI病史的患者中，垂体功能减退的程度与骨骼肌质量、体脂、生活质量和ADL的恶化程度相关。目的：TBI具有深远的临床和经济后果。损伤的常见后遗症包括神经或神经肌肉损伤、认知功能障碍、身体机能减退、体重增加或脂肪再分配，以及生活质量和整体表现下降。这些后遗症已被确定为成功康复的主要障碍。许多创伤性脑损伤患者不能完全康复，进入慢性残疾和失业的阶段。垂体功能减退综合征被广泛认识，替代疗法的重要性也被充分认识。垂体前叶功能障碍可能导致生长激素（GH）、甲状腺、糖皮质激素、性激素（男性睾酮/女性雌激素）和催乳素分泌的减少。一般来说，垂体功能减退患者表现为疲劳和体重增加或减少，并可能有一个或多个激素轴受损。中枢性甲状腺功能减退症广泛影响呼吸、心血管、神经和肌肉骨骼系统，因此与疲劳、运动耐受性差、记忆受损有关，并引起虚弱和肌病。男性性腺功能减退（睾酮缺乏）可导致身体组成、骨密度和神经社会心理功能的不良影响。男性睾酮缺乏会导致行为和认知方面的后果，包括情绪紊乱、语言流畅性下降、记忆力受损和生活质量下降。越来越多的文献表明，女性中枢性性腺功能减退患者的相对雄激素缺乏可能对瘦质量和功能产生不良影响。慢性肾上腺功能不全的体征和症状包括不适、乏力、虚弱、厌食和体重减轻。在严重和慢性病例中，患者可能有神经精神表现，如记忆丧失、器质性脑综合征、抑郁和明显的精神病。这项初步研究将包括一个横断面设计，男性和女性年龄在18-55岁之间，在TBI后6个月。对照受试者将在术后通过正常垂体功能进行鉴定。我们将测试每个受试者的身体组成、生活质量和ADL，以比较垂体功能低下与正常受试者的差异，并将垂体功能低下程度与结果差异程度联系起来。

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. Hypotheses: This protocol will investigate the effect of traumatic brain injury (TBI)-associated hypopituitarism on body composition, quality of life (QOL), and activities of daily living (ADL). We hypothesize that: 1. TBI is associated with a high degree of hypopituitarism, including growth hormone deficiency. 2. Hypopituitarism in patients with TBI is associated with diminished skeletal muscle mass and increased body fat, decreased QOL, and decreased ability to perform ADL compared to patients with normal pituitary function. 3. In patients with history of TBI, the degree of hypopituitarism correlates with the degree of deterioration in skeletal muscle mass, body fat, QOL, and ADL. Goals: TBI has profound clinical and economic consequences. Common sequelae of injury include neurologic or neuromuscular damage, cognitive dysfunction, physical deconditioning, weight gain or fat redistribution, as well as diminished quality of life and overall performance. These sequelae have been identified as major obstacles to successful rehabilitation. Many TBI patients fall short of complete recovery altogether and enter into a phase of chronic disability and unemployment. The syndrome of hypopituitarism is widely recognized, and the importance of replacement therapy well understood. Dysfunction of the anterior pituitary gland may lead to a compromise in growth hormone (GH), thyroid, glucocorticoid, sex hormone (testosterone in men/estrogen in women), and prolactin production. In general, patients with hypopituitarism present with fatigue and either weight gain or loss, and may have one or more hormone axes compromised. Central hypothyroidism widely impacts the respiratory, cardiovascular, neurologic, and musculoskeletal systems and therefore is associated with fatigue, poor exercise tolerance, impaired memory, and cause weakness and myopathy. Hypogonadism (testosterone deficiency) in men can lead to adverse affects on body composition, bone density, and neuropsychosocial function. Testosterone deficiency in men can have behavioral and cognitive consequences including mood disturbances, decreased verbal fluency, impaired memory, and poor quality of life. There is a growing literature on the relative androgen deficiency in female patients with central hypogonadism, which may have adverse consequences on lean mass and function. Signs and symptoms of chronic adrenal insufficiency include malaise, lassitude, weakness, anorexia, and weight loss. In severe and chronic cases, patients may have neuropsychiatric manifestations such as memory loss, organic brain syndrome, depression, and overt psychosis. This pilot study will consist of a cross-sectional design with men and women between 18-55 yrs old 6 months following TBI. Control subjects will be identified posthoc by normal pituitary function. We will test body composition, QOL, and ADL in each subject to compare differences in hypopituitary vs. normal subjects and also correlate degree of hypopituitarism to degree of differences in outcomes.