Endocrine therapies and hormonal dysfunction after traumatic brain injury: A scoping review.
Endocrine dysfunction is common after traumatic brain injury, and while some therapies show promise, their clinical effectiveness is inconsistent and requires further investigation.
Where it sits
this study against the rest of the desmopressin corpusSummary and findings
This scoping review evaluated the prevalence of endocrine dysfunction following traumatic brain injury (TBI) and the impact of endocrine-targeted therapies. The review included 67 studies but did not specify the doses or specific outcomes of desmopressin. The findings suggest that while some therapies show promise, their clinical application is limited by variability in study design and results.
Abstract
<h4>Background</h4>Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide, with current management strategies primarily focused on preventing secondary injury rather than modifying disease progression. Post-traumatic endocrine dysfunction has emerged as a significant and potentially treatable contributor to outcomes after TBI.<h4>Methods</h4>A scoping review was conducted following PRISMA-ScR guidelines. PubMed, Embase, Scopus, and Web of Science were searched from inception to September 2025 for clinical studies evaluating endocrine dysfunction and endocrine-targeted therapies post-TBI. Eligible studies included clinical trials and observational studies reporting either an endocrine outcome following TBI or an endocrine-targeted intervention with clinical or biochemical outcomes.<h4>Results</h4>Sixty-seven studies met the inclusion criteria. Endocrine dysfunction was common, affecting multiple hormone axes, with growth hormone (GH) deficiency being the most frequently reported deficiency; hypoprolactinemia and hyperprolactinemia were also identified and are increasingly recognized contributors to post-TBI metabolic morbidity. Growth hormone replacement therapy demonstrated improvements in cognitive function, fatigue, mood, and quality of life in several studies; however, its effects on functional outcomes and mortality were inconsistent. Progesterone showed benefit in early-phase trials but failed to demonstrate efficacy in large multicenter randomized controlled trials, an inconsistency that appears closely tied to the timing of treatment initiation after injury. Other therapies, including desmopressin and glucocorticoids, were primarily used for supportive management, with limited evidence of neuroprotective benefit.<h4>Conclusions</h4>Endocrine dysfunction after TBI is prevalent, heterogeneous, and associated with worse clinical outcomes. While endocrine therapies, particularly GH, show promise, their translation into clinical practice is limited by heterogeneity in study design, small sample sizes, and inconsistent findings. Larger, well-designed trials and consensus clinical guidelines are needed to define optimal therapeutic strategies and integrate endocrine care into the optimal management of TBI patients.
Background
This paper addresses the prevalence and impact of endocrine dysfunction following traumatic brain injury (TBI), a significant cause of morbidity and mortality. Previous studies have indicated that endocrine dysfunction can contribute to adverse outcomes after TBI, but the effectiveness of targeted therapies remains uncertain. This scoping review aims to synthesize existing evidence on the topic and identify gaps in the literature.
Methods
A scoping review was conducted following PRISMA-ScR guidelines, searching PubMed, Embase, Scopus, and Web of Science from inception to September 2025. Eligible studies included clinical trials and observational studies that reported on endocrine outcomes or interventions post-TBI. The review included a total of 67 studies.
Results
Endocrine dysfunction was found to be common among TBI patients, affecting multiple hormone axes. Growth hormone deficiency was the most frequently reported issue, with several studies indicating improvements in cognitive function, fatigue, mood, and quality of life with growth hormone replacement therapy. However, the effects on functional outcomes and mortality were inconsistent.
Interpretation
The findings suggest that while endocrine therapies, particularly growth hormone, may show promise, the variability in study designs and outcomes limits their clinical applicability. The lack of consistent evidence regarding the timing and efficacy of treatments like progesterone further complicates the interpretation of results. The review underscores the need for larger, well-designed trials to better define effective therapeutic strategies.
Key findings
- 67 studies met the inclusion criteria.
- Growth hormone deficiency was the most frequently reported deficiency.
- Growth hormone replacement therapy demonstrated improvements in cognitive function, fatigue, mood, and quality of life in several studies.
- Effects of growth hormone on functional outcomes and mortality were inconsistent.
- Progesterone showed benefit in early-phase trials but failed to demonstrate efficacy in large multicenter randomized controlled trials.
Limitations
- Heterogeneity in study design.
- Small sample sizes in included studies.
- Inconsistent findings across studies.
- Limited evidence for neuroprotective benefit of desmopressin.