Pituitary function is rarely considered in the care of patients with traumatic brain injury (TBI). Yet, TBI poses significant risk to pituitary function given the gland's encasement within the sella, its delicate infundibular-hypothalamic structures and vulnerable vascular supply. Autopsy studies of fatal head injury victims confirm that up to one third sustain pituitary necrosis and hundreds of case reports document chronic post-traumatic pituitary failure. The long-term neurobehavioral problems that plague a majority of TBI victims are quite similar to those of patients with hypopituitarism. It is the primary hypothesis of this study that many TBI victims suffer from unrecognized pituitary dysfunction that acutely and chronically compounds the initial brain injury and limits maximal recovery. The major hypotheses being tested in this study are that i) post-traumatic pituitary failure, both acute and chronic, results primarily from a vascular insult to the pituitary gland and/or its hypothalamic-infundibular connections; ii) in the acute phase of TBI such injury can result in acute secondary adrenal insufficiency, iii) in the chronic phase of TBI such injury can result in long-term hypopituitarism, and iv) treatment of pituitary hormone deficiencies will improve neurobehavioral functioning and quality of life in the chronic post-traumatic state. These hypotheses will be tested in a three-phase study. In the first phase, acutely post-injury, subjects will undergo serial determinations of adrenocortical function to diagnose and treat acute adrenal insufficiency. Patients found to have inappropriately low cortisol levels, will be randomized to placebo or hydrocortisone therapy for 48 hours, and changes in blood pressure and vasopressor requirements will be monitored. Pituitary/hypothalamic MRIs will also be performed at 10 days and 6 months post-injury to assess for acute structural lesions and chronic pituitary volumetric changes. In the second phase, at 2 and 6 months post-injury, pituitary function tests will be performed. Hormone deficient patients will be placed on hormone replacement except for growth hormone (GH) after the 2-month time point. In the third phase, from 6 to 12 months post-injury, TBI patients with GH deficiency or GH insufficiency, who have memory impairment, concentration deficits, depression, anxiety or fatigue will be entered into a double-blind placebo-controlled GH replacement therapy trial to assess changes in these neurobehavioral and quality of life complaints. By diagnosing and treating both acute and chronic traumatic neuroendocrine deficiencies, this study may dramatically improve the lone-term prognosis of many TBI patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS040777-03
Application #
6740773
Study Section
Special Emphasis Panel (ZRG1-BDCN-1 (01))
Program Officer
Gilbert, Peter R
Project Start
2002-04-01
Project End
2007-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
3
Fiscal Year
2004
Total Cost
$507,517
Indirect Cost
Name
La Biomed Research Institute/ Harbor UCLA Medical Center
Department
Type
DUNS #
069926962
City
Torrance
State
CA
Country
United States
Zip Code
90502
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Bavisetty, Sumati; Bavisetty, Supriya; McArthur, David L et al. (2008) Chronic hypopituitarism after traumatic brain injury: risk assessment and relationship to outcome. Neurosurgery 62:1080-93;discussion 1093-4
Batzdorf, Ulrich; Khoo, Larry T; McArthur, David L (2007) Observations on spine deformity and syringomyelia. Neurosurgery 61:370-7;discussion 377-8
Kelly, Daniel F; McArthur, David L; Levin, Harvey et al. (2006) Neurobehavioral and quality of life changes associated with growth hormone insufficiency after complicated mild, moderate, or severe traumatic brain injury. J Neurotrauma 23:928-42
Cohan, Pejman; Wang, Christina; McArthur, David L et al. (2005) Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med 33:2358-66
Qu, Xiao-Dan; Gaw Gonzalo, Irene T; Al Sayed, Mohammed Y et al. (2005) Influence of body mass index and gender on growth hormone (GH) responses to GH-releasing hormone plus arginine and insulin tolerance tests. J Clin Endocrinol Metab 90:1563-9