Effect of growth hormone replacement therapy on cognition after traumatic brain injury

Abstract

Traumatic brain injury (TBI) is a major public health issue, and yet medical science has little to offer for the persistent symptoms that prevent many of these individuals from fully re-entering society. Post-traumatic hypopituitarism, and specifically growth hormone deficiency (GHD), has been found in a large percentage of individuals with chronic moderate to severe TBI. Presently, there are no published treatment studies of hormone replacement in this population. In this study, 83 subjects with chronic TBI were screened for hypopituitarism. Forty-two subjects were found to have either GHD or GH insufficiency (GHI), of which 23 agreed to be randomized to either a year of GH replacement or placebo. All subjects completed the study with no untoward side effects from treatment. A battery of neuropsychological tests and functional measures were administered before and after treatment. Improvement was seen on the following tests: Dominant Hand Finger Tapping Test, Wechsler Adult Intelligence Scale III-Information Processing Speed Index, California Verbal Learning Test II, and the Wisconsin Card Sorting Test (executive functioning). The findings of this pilot study provide preliminary evidence suggesting that some of the cognitive impairments observed in persons who are GHD/GHI after TBI may be partially reversible with appropriate GH replacement therapy.

Figures

FIG. 1.

Peak growth hormone response to glucagon stimulation test prior to rhGH replacement (rhGH, recombinant human growth hormone; IGF-1, insulin-like growth factor-1).

FIG. 2.

Initial versus final IGF-1 levels after 1 year of replacement with rhGH or treatment with placebo (IGF-1, insulin-like growth factor-1; rhGH, recombinant human growth hormone).

FIG. 3.

Finger Tapping–Dominant Hand. Significant improvements were observed for participants treated with active rhGH, but not for participants receiving placebo. The interaction between treatment group and time tested was significant, indicating differential improvement in performance of the treatment group versus the placebo group. Post-hoc analysis showed significant improvement in motor speed from baseline to 1 year for the active rhGH group, but not for the placebo group (rhGH, recombinant human growth hormone; GH, growth hormone).

FIG. 4.

Processing Speed Index. Significant improvements were observed for participants treated with active rhGH. While a significant improvement was seen for the placebo group from baseline to 6 months, the improvements from baseline to 12 months, and from 6 months to 12 months, were not significant. Pairwise comparisons indicated that the active rhGH group demonstrated improvement from baseline to 1 year. The placebo group showed some improvement from baseline to 6 months (rhGH, recombinant human growth hormone; GH, growth hormone).

FIG. 5.

Wisconsin Card Sorting Test–Total Correct. A three-way interaction for time by group by the peak GH response to GST was observed. Post-hoc pairwise comparisons indicated a trend in which the active rhGH group showed significantly greater scores than the placebo group at 12 months, although this difference failed to reach statistical significance (rhGH, recombinant human growth hormone; GH, growth hormone; GST, glucagon stimulation test).

FIG. 6.

California Verbal Learning Test-II–Trials 1–5 (CVLT-II). The interactions between time and treatment group were statistically significant using multivariate analysis of covariance. A significant improvement over time for learning and memory was demonstrated on the CVLT-II for the rhGH group, but not for the placebo group (rhGH, recombinant human growth hormone).