When Charles Wilkinson thinks about soldiers suffering from post-traumatic stress disorder (PTSD) his mind jumps to a pea-size structure tucked behind the bridge of the nose and ensconced below the base of the brain. There the pituitary gland serves as the master regulator of the human endocrine system, producing vital hormones that influence growth and developmentexcept when something goes awry. Wilkinson and a small cadre of scientists are studying whether traumatic brain injury (TBI) caused by battlefield explosions can damage soldiers pituitary glands in ways that cause lasting health problems. Preliminary work that Wilkinson presented to the Department of Veterans Affairs in May indicates that soldiers with TBI go on to develop hormonal deficiencies and symptoms that could be mistaken for PTSD as much as 40 percent of the time. The startling finding is based on only a couple dozen soldiers and needs to be replicated within a larger group, but several other small studies over the past six years suggest a similar relationship. The ostensible link might augment our understanding of what causes the complex constellation of symptoms associated with PTSD. Combat is not the only arena in which scientists have found a connection between TBI and hormone dysfunction. Several studies have suggested that head injuries on the sports field or in car accidents are linked with an increase in pituitary disorders. Based on those results, Wilkinson a neuroendocrinologist at the VA Puget Sound Health Care System in Seattle started looking for clues that soldiers suffering from TBI following blast exposures were also suffering from treatable disorders like hormone deficiency. Such patients may have PTSD-like symptoms including depression, anxiety and trouble focusing, which could be treated with hormone replacement therapy that might boost their ability to focus, libido and quality of life. The theory, Wilkinson readily admits, is still in its early days. Only a handful of other researchers are looking into the possible link, and all the studies have tiny sample sizes, usually looking at a couple dozen soldiers. But if even a small fraction of TBI patients have undiagnosed pituitary disorders, perhaps they could get help that would substantially improve their health, he says. Among civilians, estimates of the prevalence of TBI-related pituitary disorders vary widely, ranging between 15 and 68 percent of patients. That range reflects differences in diagnostic criteria and potential factors like the timing of the assessment, says Nicholas Tritos, a neuroendocrinologist at Massachusetts General Hospital who is studying such disorders among both civilian and military populations. Yet those numbers raise questions about how often such disorders may occur, and not resolve themselves naturally, among soldiers with head trauma. In one recent study Tritos found that 39 percent of the blast victims (seven patients) had hormonal disorders. Preliminary findings from Wilkinsons ongoing study suggest that men (he only studied male service members) who suffered from blast-related TBI were more likely to have pituitary disorders, too. Among 27 blast victims, 44 percent had pituitary disorders whereas only 7 percent of a group of 14 military personnel without blast-related concussion had pituitary disorders. A separate study of British soldiers spearheaded by researchers at Imperial College London in 2013 had comparable results. Six of 19 soldiers with blast-related TBI had pituitary deficiencies whereas only one of 39 soldiers in the nonblast control group had these disorders. No larger studies are currently planned. It is difficult to conduct such research among service members, partly because they may suffer from other health issues, says Wilkinson, who has struggled to recruit the hundreds of soldiers he originally hoped to include in his analysis. In the U.K. soldiers are no longer deployed to active war zones so there are no new blast victims available for larger studies there, says Tony Goldstone, an endocrinologist and an author of the 2013 British study. Additionally, whether the patient is military or civilian there are still unanswered questions about exactly how a head injury could damage the pituitary gland in the first place. Its central placement in the head typically protects it from damage but a delicate stalk connects the gland to the brain and some experts hypothesize that this connection or the gland itself may be damaged by a violent blow or blast. Inflammation or other ruptured connections could also be factors. Because the damage is not visible on standard magnetic resonance imaging (MRI), however, researchers may have to depend on animal models to glean further insights. The few experts working in this area say more answers will likely come from studying civilian populations with TBI in the coming years. For his part, Wilkinson says someone else will have to continue the work. He plans to retire in September 2017 at the age of 72.
Scientific American, 13 July 2016 ;http://www.sciam.com ;