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      Chronic Hypopituitarism Associated with Increased Postconcussive Symptoms Is Prevalent after Blast-Induced Mild Traumatic Brain Injury

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          Abstract

          The most frequent injury sustained by US service members deployed to Iraq or Afghanistan is mild traumatic brain injuries (mTBI), or concussion, by far most often caused by blast waves from improvised explosive devices or other explosive ordnance. TBI from all causes gives rise to chronic neuroendocrine disorders with an estimated prevalence of 25–50%. The current study expands upon our earlier finding that chronic pituitary gland dysfunction occurs with a similarly high frequency after blast-related concussions. We measured circulating hormone levels and accessed demographic and testing data from two groups of male veterans with hazardous duty experience in Iraq or Afghanistan. Veterans in the mTBI group had experienced one or more blast-related concussion. Members of the deployment control (DC) group encountered similar deployment conditions but had no history of blast-related mTBI. 12 of 39 (31%) of the mTBI participants and 3 of 20 (15%) veterans in the DC group screened positive for one or more neuroendocrine disorders. Positive screens for growth hormone deficiency occurred most often. Analysis of responses on self-report questionnaires revealed main effects of both mTBI and hypopituitarism on postconcussive and posttraumatic stress disorder (PTSD) symptoms. Symptoms associated with pituitary dysfunction overlap considerably with those of PTSD. They include cognitive deficiencies, mood and anxiety disorders, sleep problems, diminished quality of life, deleterious changes in metabolism and body composition, and increased cardiovascular mortality. When such symptoms are due to hypopituitarism, they may be alleviated by hormone replacement. These findings suggest consideration of routine post-deployment neuroendocrine screening of service members and veterans who have experienced blast-related mTBI and are reporting postconcussive symptoms.

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          Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care.

          The current combat operations in Iraq and Afghanistan have involved U.S. military personnel in major ground combat and hazardous security duty. Studies are needed to systematically assess the mental health of members of the armed services who have participated in these operations and to inform policy with regard to the optimal delivery of mental health care to returning veterans. We studied members of four U.S. combat infantry units (three Army units and one Marine Corps unit) using an anonymous survey that was administered to the subjects either before their deployment to Iraq (n=2530) or three to four months after their return from combat duty in Iraq or Afghanistan (n=3671). The outcomes included major depression, generalized anxiety, and post-traumatic stress disorder (PTSD), which were evaluated on the basis of standardized, self-administered screening instruments. Exposure to combat was significantly greater among those who were deployed to Iraq than among those deployed to Afghanistan. The percentage of study subjects whose responses met the screening criteria for major depression, generalized anxiety, or PTSD was significantly higher after duty in Iraq (15.6 to 17.1 percent) than after duty in Afghanistan (11.2 percent) or before deployment to Iraq (9.3 percent); the largest difference was in the rate of PTSD. Of those whose responses were positive for a mental disorder, only 23 to 40 percent sought mental health care. Those whose responses were positive for a mental disorder were twice as likely as those whose responses were negative to report concern about possible stigmatization and other barriers to seeking mental health care. This study provides an initial look at the mental health of members of the Army and the Marine Corps who were involved in combat operations in Iraq and Afghanistan. Our findings indicate that among the study groups there was a significant risk of mental health problems and that the subjects reported important barriers to receiving mental health services, particularly the perception of stigma among those most in need of such care. Copyright 2004 Massachusetts Medical Society
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            Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia.

            Ken Ho (2007)
            The GH Research Society held a Consensus Workshop in Sydney, Australia, 2007 to incorporate the important advances in the management of GH deficiency (GHD) in adults, which have taken place since the inaugural 1997 Consensus Workshop. Two commissioned review papers, previously published Consensus Statements of the Society and key questions were circulated before the Workshop, which comprised a rigorous structure of review with breakout discussion groups. A writing group transcribed the summary group reports for drafting in a plenary forum on the last day. All participants were sent a polished draft for additional comments and gave signed approval to the final revision. Testing for GHD should be extended from hypothalamic-pituitary disease and cranial irradiation to include traumatic brain injury. Testing may indicate isolated GHD; however, idiopathic isolated GHD occurring de novo in the adult is not a recognized entity. The insulin tolerance test, combined administration of GHRH with arginine or growth hormone-releasing peptide, and glucagon are validated GH stimulation tests in the adult. A low IGF-I is a reliable diagnostic indicator of GHD in the presence of hypopituitarism, but a normal IGF-I does not rule out GHD. GH status should be reevaluated in the transition age for continued treatment to complete somatic development. Interaction of GH with other axes may influence thyroid, glucocorticoid, and sex hormone requirements. Response should be assessed clinically by monitoring biochemistry, body composition, and quality of life. There is no evidence that GH replacement increases the risk of tumor recurrence or de novo malignancy.
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              The development of a Clinician-Administered PTSD Scale

              Several interviews are available for assessing PTSD. These interviews vary in merit when compared on stringent psychometric and utility standards. Of all the interviews, the Clinician-Administered PTSD Scale (CAPS-1) appears to satisfy these standards most uniformly. The CAPS-1 is a structured interview for assessing core and associated symptoms of PTSD. It assesses the frequency and intensity of each symptom using standard prompt questions and explicit, behaviorally-anchored rating scales. The CAPS-1 yields both continuous and dichotomous scores for current and lifetime PTSD symptoms. Intended for use by experienced clinicians, it also can be administered by appropriately trained paraprofessionals. Data from a large scale psychometric study of the CAPS-1 have provided impressive evidence of its reliability and validity as a PTSD interview.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/478584
                URI : http://frontiersin.org/people/u/45770
                URI : http://frontiersin.org/people/u/696
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                19 February 2018
                2018
                : 9
                : 72
                Affiliations
                [1] 1Department of Psychiatry and Behavioral Sciences, University of Washington , Seattle, WA, United States
                [2] 2Geriatric Research, Education and Clinical Center (GRECC), VA Puget Sound Health Care System, U.S. Department of Veterans Affairs , Seattle, WA, United States
                [3] 3VISN 20 Northwest Network Mental Illness Research, Education, and Clinical Center (MIRECC), VA Puget Sound Health Care System, U.S. Department of Veterans Affairs , Seattle, WA, United States
                Author notes

                Edited by: Marco Sarà, San Raffaele Cassino, Italy

                Reviewed by: Roberto Piperno, Physical Medicine and Rehabilitation, Italy; Akinobu Nakamura, Hokkaido University, Japan

                *Correspondence: Charles W. Wilkinson, wilkinso@ 123456uw.edu , charles.wilkinson@ 123456va.gov

                Present address: Arundhati Undurti, The Vancouver Clinic, Vancouver, WA, United States

                Specialty section: This article was submitted to Neurotrauma, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2018.00072
                5825904
                29515515
                a64056fa-547b-4b9b-8171-ebf287eccb60
                Copyright © 2018 Undurti, Colasurdo, Sikkema, Schultz, Peskind, Pagulayan and Wilkinson.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 November 2017
                : 31 January 2018
                Page count
                Figures: 2, Tables: 5, Equations: 0, References: 109, Pages: 13, Words: 10867
                Funding
                Funded by: U.S. Department of Defense 10.13039/100000005
                Award ID: W81XWH-11-1-0278
                Funded by: U.S. Department of Veterans Affairs 10.13039/100000738
                Award ID: 5 I01 RX 000509, IK2CX000516, B77421
                Categories
                Neuroscience
                Original Research

                Neurology
                traumatic brain injury,blast,concussion,pituitary,military,posttraumatic stress disorder,growth hormone deficiency,veterans

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