CONSEQUENCES OF HYPOPITUITARISM FOLLOWING TRAUMATIC BRAIN INJURY (TBI)

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 假设： 本方案将研究创伤性脑损伤（TBI）相关垂体功能减退症对身体成分、生活质量（QOL）和日常生活活动（ADL）的影响。我们假设： 1. TBI与高度的垂体功能减退有关，包括生长激素缺乏症。 2. 与垂体功能正常的患者相比，TBI患者的垂体功能减退与骨骼肌质量减少、体脂增加、QOL降低和ADL能力降低有关。 3. 在有外伤史的患者中，垂体功能减退的程度与骨骼肌质量、体脂、生活质量和日常生活能力的恶化程度相关。 目标： 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、身体失调、体重增加或脂肪重新分布，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TBI患者无法完全康复，并进入慢性残疾和失业阶段。 垂体功能减退综合征已被广泛认识，替代治疗的重要性也已被充分理解。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）和催乳素产生受损。一般来说，垂体功能减退症患者表现为疲劳和体重增加或减轻，并且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系统、心血管系统、神经系统和肌肉骨骼系统，因此与疲劳、运动耐量差、记忆力受损相关，并导致虚弱和肌病。男性性腺功能减退症（睾酮缺乏症）可导致对身体成分、骨密度和神经心理社会功能的不良影响。男性中的睾酮缺乏可导致行为和认知后果，包括情绪障碍、语言流畅性下降、记忆力受损和生活质量差。越来越多的文献报道中枢性性腺功能减退症女性患者存在雄激素相对缺乏，这可能对瘦体重和功能产生不良影响。慢性肾上腺功能不全的症状和体征包括不适、倦怠、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症状，如记忆力丧失、器质性脑综合征、抑郁症和明显的精神病。 该试点研究将包括一项横断面设计，其中男性和女性年龄在18-55岁之间，TBI后6个月。对照受试者将在术后通过正常垂体功能进行识别。我们将测试每个受试者的身体成分、QOL和ADL，以比较垂体功能减退与正常受试者的差异，并将垂体功能减退的程度与结果的差异程度相关联。

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 QOL. 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 years 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.