Growth Hormone Alters Brain Morphometry, Connectivity, and Behavior in Subjects with Fatigue after Mild Traumatic Brain Injury

Pituitary dysfunction with reduced growth hormone (GH) secretion is common in patients following traumatic brain injury (TBI), and these patients often develop chronic symptoms including fatigue and altered cognition. We examined 18 subjects with a history of mild TBI, fatigue, and insufficient GH secretion. Subjects received GH replacement in a year-long, double-blind, placebo-controlled, crossover study, and were assessed for changes in physical performance, body composition, resting energy expenditure, fatigue, sleep, mood, and neuropsychological status. Additionally, magnetic resonance imaging (MRI) was used to assess changes in brain structure and resting state functional connectivity. GH replacement resulted in decreased fatigue, sleep disturbance, and anxiety, as well as increased resting energy expenditure, improved body composition, and altered perception of submaximal effort when performing exercise testing. Associated brain changes included increased frontal cortical thickness and gray matter volume and resting state connectivity changes in regions associated with somatosensory networks. GH replacement altered brain morphology and connectivity and reduced fatigue and related symptoms in mild TBI patients. Additional studies are needed to understand the mechanisms causing TBI-related fatigue and symptom relief with GH replacement.