Outcomes of recombinant growth hormone therapy in the traumatic brain injury population: A scoping review

Background: Post-traumatic hypopituitarism (PTHP), including growth hormone deficiency (GHD), is a prevalent and underdiagnosed complication of traumatic brain injury (TBI), resulting in substantial morbidity. Emerging evidence suggests that recombinant human growth hormone (rhGH) therapy may provide benefit for patients with confirmed GHD, and also those with growth hormone insufficiency (GHI), abnormal growth hormone secretion (AGHS), or Brain Injury Associated Fatigue and Altered Cognition (BIAFAC), even when peak growth hormone response to growth hormone stimulation testing is above traditional GHD diagnostic cutoffs in these patients. Objective: To conduct a scoping review evaluating the effects of rhGH in adults with TBI, including those classified as GHD, GHI, AGHS, or BIAFAC, on clinical, functional, and neurobiological outcomes. Methods: A comprehensive search of PubMed/MEDLINE was performed using a peer-reviewed search strategy. Studies were screened in duplicate. Eligible studies included clinical trials, observational studies, and case series, reporting rhGH use in adults with a history of TBI, with or without GHD. Outcomes included quality of life, neuropsychological performance, physical functioning, biochemical markers, and neuroimaging data. Results: Eleven studies met inclusion criteria: two double-blind, randomized, placebo-controlled trials; one double-blind, randomized, placebo-controlled crossover study; one double-blind, non-randomized, placebo-controlled trial; two non-randomized controlled trials; three retrospective cohort studies; and two open-label, single-arm trials. Across the studies reviewed, the researchers reported improvements in insulin-like growth factor-1 (IGF-1) levels, fatigue, mood, physical performance, and cognition. Structural and functional neuroimaging changes following rhGH were also reported, including increased cortical thickness and gray matter volume, and improved functional connectivity of somatosensory networks. Symptomatic improvement as well as improvements in objective measures were described among patients who did not meet diagnostic cut-point criteria for GHD. Conclusion: Evidence suggests that rhGH may confer benefit in a broad range of symptomatic TBI patients, including those with peak growth hormone values in ranges overlapping with normal, healthy controls. Larger, controlled studies are warranted to validate these findings and inform clinical guidelines.