High Prevalence of Chronic Pituitary and Target-Organ Hormone Abnormalities after Blast-Related Mild Traumatic Brain Injury

Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least 1 year after injury, in 25–50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP) to be unrelated to injury severity. Growth hormone deficiency (GHD) and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI), an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least 1 year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I) levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and rehabilitation

Hypopituitarism caused by blast-related mTBI may result in PTSD-like symptoms

Recent studies in civilian populations have found the prevalence of hypopituitarism as a result of head injuries from all causes to be between 25 and 50%. However, the neuroendocrine effects of concussion, or mild traumatic brain injury (mTBI) due to explosive blasts have received relatively little attention. Blast-related mTBI is the most common injury sustained by U.S. troops deployed to Iraq or Afghanistan. Approximately 20% of returning service members have experienced one or more blast-related concussions. Posttraumatic hypopituitarism (PTHP) has been shown to result in several symptoms that overlap considerably with those of PTSD. These include fatigue, depression, sexual dysfunction, anxiety, social isolation, and detrimental effects on sleep, learning and memory, body composition, and quality of life. We are investigating the prevalence of PTHP in two groups of Veterans of deployment to Iraq or Afghanistan. Members of the TBI group sustained at least one blast-related mTBI; members of the deployment control (DC) group experienced similar extreme conditions but did not experience a blast concussion. We conducted screening for growth hormone deficiency (GHD), hypogonadism, thyroid deficiency, and secondary adrenal insufficiency (sAI) by measuring basal blood samples and by testing for GHD and sAI with the glucagon stimulation test. Eighteen of 44 (36.4%) TBI group participants and seven of 32 (15.6%) DC group participants screened positive for pituitary hormone deficits. GHD and sAI were observed most frequently. We used behavioral self-reports and cognitive testing to examine symptom prevalence. Veterans with TBI and pituitary dysfunction endorsed more severe and/or frequent symptoms than those in the TBI group without hypopituitarism or the DC group. These findings and observations suggest that screening for pituitary dysfunction after head injuries holds promise for not only recognizing appropriate treatment options that might not otherwise be considered, but also facilitating recovery and rehabilitation of these service members.DoD CDMRP Concept Award PT090753 and VA RR&D Merit Award to CWW; Geriatric Research, Education and Clinical Center, and the Research and Development Service of the VA Puget Sound Health Care System; the VA Northwest Network Mental Illness Research, Education and Clinical Center; and the University of Washington Alzheimerʼs Disease Research Center NIA AG05136

Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III Criteria for the Metabolic Syndrome

The underlying pathophysiology of the metabolic syndrome is the subject of debate, with both insulin resistance and obesity considered as important factors. We evaluated the differential effects of insulin resistance and central body fat distribution in determining the metabolic syndrome as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III. In addition, we determined which NCEP criteria were associated with insulin resistance and central adiposity. The subjects, 218 healthy men (n = 89) and women (n = 129) with a broad range of age (26&#8211;75 years) and BMI (18.4&#8211;46.8 kg/m2), underwent quantification of the insulin sensitivity index (Si) and intra-abdominal fat (IAF) and subcutaneous fat (SCF) areas. The metabolic syndrome was present in 34 (15.6%) of subjects who had a lower Si [median: 3.13 vs. 6.09 × × 10&#8211;5 min&#8211;1/(pmol/l)] and higher IAF (166.3 vs. 79.1 cm2) and SCF (285.1 vs. 179.8 cm2) areas compared with subjects without the syndrome (P < 0.001). Multivariate models including Si, IAF, and SCF demonstrated that each parameter was associated with the syndrome. However, IAF was independently associated with all five of the metabolic syndrome criteria. In multivariable models containing the criteria as covariates, waist circumference and triglyceride levels were independently associated with Si and IAF and SCF areas (P < 0.001). Although insulin resistance and central body fat are both associated with the metabolic syndrome, IAF is independently associated with all of the criteria, suggesting that it may have a pathophysiological role. Of the NCEP criteria, waist circumference and triglycerides may best identify insulin resistance and visceral adiposity in individuals with a fasting plasma glucose < 6.4 mmol/l

High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury

Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least one year after injury, in 25-50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP) to be unrelated to injury severity. Growth hormone deficiency (GHD) and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI), an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least one year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I) levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and rehabilitation