Principle Investigator: Daniel F. Kelly, M.D.
Institution: John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, CA
Title: Hypopituitarism in Retired Professional Football Players
Abstract:More than 1.2 million Americans sustain a traumatic brain injury (TBI) annually, the majority of which are mild TBIs (MTBI) or cerebral concussions. Repeat concussions have been identified as a risk factor for the occurrence (or early expression) of neurodegenerative dementing disorders, including Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD). The pathophysiology of these disorders is unclear and warrants further investigation.
One particular area that has received little attention is the concept that repeat MTBI can lead to pituitary dysfunction (hypopituitarism) which in turn can be a direct cause of reduced general health, poor quality of life and sexual dysfunction. This linkage between TBI, hypopituitarism, reduced health and poor quality of life is already well-established for individuals sustaining a single moderate or severe TBI; recent studies indicate that these more severe TBIs lead to hypopituitarism in up to one third of individuals. We propose to study a cohort of retired NFL players who have documented poor quality of life to determine the relationship between these complaints, their concussion (MTBI) history, their pituitary hormonal function and sexual function. We hypothesize that the number of MTBIs sustained in their NFL career will correlate with the rate of hypopituitarism and that untreated hypopituitarism in these individuals will be associated with poor quality of life and general health, neuro-behavioral impairment and sexual dysfunction. This study will also determine the possible benefits of physiological hormone replacement therapy in retirees with diagnosed hypopituitarism. Given that our preliminary studies of retired players suggest recurrent concussions are a risk factor for late-life memory impairment, MCI and depression, and the increasingly recognized entity of post-TBI hypopituitarism, a possible link between MTBI and pituitary dysfunction warrants study. Utilizing neurobehavioral and quality of life testing, a sexual function survey, pituitary hormonal testing and DEXA scanning, this study will address the following specific aims:
Specific Aim 1: To determine if chronic hypopituitarism and sexual dysfunction in retired players with poor quality of life is related to MTBIs sustained during their NFL career.
Hypothesis: In retired players with poor quality of life on SF-36 testing, hypopituitarism and sexual dysfunction will occur in approximately 25% of individuals who have sustained MTBIs. The frequency of hypopituitarism and sexual dysfunction will increase with increasing numbers of MTBIs. The hormonal axes most affected will be the somatotroph and gonadotroph axes.
Specific Aim 2: To define the impact of hypopituitarism on neurobehavioral measures, quality of life, sexual function, metabolic syndrome and body composition in retired players who have had MTBI.
Hypothesis: Retired players with hypopituitarism will show higher rates of neurobehavioral impairment, poorer quality of life, increased sexual dysfunction, poorer body composition and a higher incidence of metabolic syndrome than those without hypopituitarism.
Specific Aim 3: To determine the impact of hormone replacement on neurobehavioral function, quality of life, sexual function, metabolic syndrome and body composition in hormonally-deficient NFL retirees with prior MTBI.
Hypothesis: Hormonally deficient retirees administered physiological replacement doses of GH, testosterone, thyroxin and/or corticosteroids will show improvements in neurobehavioral function, quality of life, sexual function, metabolic syndrome and body composition.