This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
2M01RR000070-45
Application #
7605239
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2007-02-15
Project End
2007-11-30
Budget Start
2007-02-15
Budget End
2007-11-30
Support Year
45
Fiscal Year
2007
Total Cost
$11,704
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Evangelou, Evangelos (see original citation for additional authors) (2018) Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits. Nat Genet 50:1412-1425
Doherty, Aiden; Smith-Byrne, Karl; Ferreira, Teresa et al. (2018) GWAS identifies 14 loci for device-measured physical activity and sleep duration. Nat Commun 9:5257
Askie, Lisa M; Darlow, Brian A; Finer, Neil et al. (2018) Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA 319:2190-2201
Frayling, Timothy M; Beaumont, Robin N; Jones, Samuel E et al. (2018) A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure. Cell Rep 23:327-336
Latva-Rasku, Aino; Honka, Miikka-Juhani; Stan?áková, Alena et al. (2018) A Partial Loss-of-Function Variant in AKT2 Is Associated With Reduced Insulin-Mediated Glucose Uptake in Multiple Insulin-Sensitive Tissues: A Genotype-Based Callback Positron Emission Tomography Study. Diabetes 67:334-342
Srinivasan, Lakshmi; Page, Grier; Kirpalani, Haresh et al. (2017) Genome-wide association study of sepsis in extremely premature infants. Arch Dis Child Fetal Neonatal Ed 102:F439-F445
Di Fiore, Juliann M; Martin, Richard J; Li, Hong et al. (2017) Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort. J Pediatr 186:49-56.e1
Denson, Lee A; McDonald, Scott A; Das, Abhik et al. (2017) Early Elevation in Interleukin-6 is Associated with Reduced Growth in Extremely Low Birth Weight Infants. Am J Perinatol 34:240-247
Holmes, Michael V; Pulit, Sara L; Lindgren, Cecilia M (2017) Genetic and epigenetic studies of adiposity and cardiometabolic disease. Genome Med 9:82
Younge, Noelle; Goldstein, Ricki F; Bann, Carla M et al. (2017) Survival and Neurodevelopmental Outcomes among Periviable Infants. N Engl J Med 376:617-628

Showing the most recent 10 out of 589 publications