Pituitary hormone abnormalities are not uncommon among individuals who have sustained a traumatic brain injury (TBI), particularly among the military population which has a higher prevalence of lifetime TBI due to the risks associated with a military career. The diagnosis and treatment of these hormone abnormalities (also known as post-traumatic hypopituitarism or PTHP) is further complicated by numerous comorbidities (discussed below) endemic among individuals with a history of military service whose symptoms are similar to those of PTHP. This updated review discusses the unique pathophysiology of military-related TBI due to high frequency of blast TBI and multiple lifetime TBI, comorbidities within military and Veteran populations, and how these factors influence and are influenced by PTHP, including updated findings on military TBI incidence and PTHP prevalence. 0000-0002-9844-0375.

Objective: The prevalence of neuroendocrine dysfunction (NED) following mild traumatic brain injury (mTBI) remains obscure, with widely varying prevalence estimates. This study aimed to determine prevalence of NED among central hypogonadism, central hypothyroidism, and growth hormone deficiency (GHD) in active-duty military service members (SMs) receiving comprehensive TBI and psychological health care and characterize TBI burden, neurobehavioral symptom severity, and NED associations. Methods: Retrospective analysis of baseline, fasting morning serum screening labs of thyroid, gonadal, and growth hormone axes obtained from SMs attending a 4-week treatment program for TBI. NED prevalence was characterized in those who completed full tri-axis screening as well as GHD and central hypogonadism screening independently. Results: Of 1,832 TBI-screened SMs, 493 completed full neuroendocrine testing. Dual-clinician review confirmed NED in 45 (9.1%; 95% CI [6.9%, 12.0%]). Central hypogonadism (n = 33, 6.7%) was most common, followed by central hypothyroidism (n = 10, 2.0%); Screen-positive suspected GHD was 0.2% (1/493); no cases were confirmed by dynamic stimulation testing, so the true prevalence of GHD cannot be determined in this cohort. NED was associated with increased time since injury (OR = 4.15, p<.001) and fewer lifetime TBIs (OR = 0.66, p=.008), but not neurobehavioral symptoms or cognitive function. Conclusions: In the largest military TBI cohort with full NED screening to date, confirmed post-traumatic hypopituitarism prevalence was 9.1%. GHD was least common by IGF-1 (0.2%) screening, but its true prevalence remains indeterminate without systematic stimulation testing. Findings refine prevalence estimates for NED after military mTBI and emphasize the need for standardized diagnostic approaches prioritizing gonadal and thyroid axes.

Traumatic brain injury (TBI) constitutes one of the primary causes of mortality globally. While many survivors fully recover, others experience several chronic complications that, if left untreated, negatively affect the patient's quality of life. Among these, post-traumatic hypopituitarism (PTHP) represents a common yet poorly recognized condition. The subtle, non-specific nature of pituitary dysfunction symptomatology, its overlap with similar disorders subsequent to TBI, and the lack of sensitive diagnostic tools are the main factors resulting in underdiagnosis of PTHP. The aim of this review is to summarize the existing knowledge, potential clinical utility, and limitations of serum biomarkers that may serve as reliable, minimally invasive tools for assessing pituitary function in the post-TBI period or even predicting late-onset deficiencies. These biomarkers, originating from neuronal damage or the inflammatory response following pituitary injury, can be co-evaluated with basal levels of pituitary and target organs hormones to accurately establish the diagnosis of the condition. Additionally, this review also provides an overview of emerging biomarkers that are currently under investigation and may be incorporated into clinical practice in the future.

Post-Traumatic Stress Disorder (PTSD) is a psychological disorder triggered by extreme traumatic events. It is characterized by impaired cognitive function and neuroendocrine dysfunction, particularly dysregulation of the hypothalamic-pituitary-adrenal axis. In recent years, the role of vitamin D in neuroprotection and cognitive function has garnered increasing interest; however, its relationship with hypothalamic-pituitary-adrenal (HPA) axis hormone levels in patients with post-traumatic stress disorder (PTSD) remains poorly understood. This study aimed to investigate the correlation between serum vitamin D levels and HPA axis hormones in patients with PTSD. A total of 96 patients with severe trauma admitted to Rizhao People's Hospital between March 2022 and December 2024 were enrolled and categorized into PTSD and non-PTSD groups according to diagnostic criteria. PTSD symptoms were evaluated using the PTSD Checklist-Civilian Version. Serum levels of 25-hydroxyvitamin D, corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol were measured. Spearman's correlation analysis and receiver operating characteristic curves were employed to assess associations between vitamin D, HPA axis biomarkers, and PCL-C Scores. The results showed that serum 25-hydroxyvitamin D levels were significantly lower in the PTSD group compared to the non-PTSD group (P < 0.001), while CRH and ACTH levels were significantly higher, and cortisol levels were significantly lower (P < 0.001). Spearman correlation analysis indicated that vitamin D levels were negatively correlated with CRH and ACTH levels and positively correlated with cortisol levels (P < 0.05). ROC curve analysis revealed that serum 25-hydroxyvitamin D levels have diagnostic potential for PTSD, with a cutoff value of 16.32 ng/mL, an AUC of 0.698, sensitivity of 86.2%, and specificity of 51.1%. This study demonstrated a correlation between serum vitamin D levels and HPA axis hormone levels in patients with PTSD, suggesting that vitamin D deficiency may be associated with HPA axis dysregulation in PTSD. These findings underscore a potential link between vitamin D deficiency and PTSD, warranting further investigation into the role of vitamin D in the disorder's pathophysiology and its potential as a therapeutically modifiable factor.

India experiences the highest number of road traffic fatalities globally. Acquired hypopituitarism is a common sequela in patients who sustain traumatic brain injury (TBI). This study aimed to investigate the prevalence and imaging characteristics of hypopituitarism in patients with TBI at a tertiary care centre in North India. Our prospective study included 76 patients with TBI (mild, moderate, or severe), whom we followed for 24 weeks at a tertiary care centre in North India. All included subjects underwent assessments of anterior pituitary hormones (LH, FSH, TSH, T4, cortisol, testosterone, estrogen) at baseline and again at 24 weeks, as well as an MRI. Those who had low cortisol level were subjected to glucagon stimulation test and cortisol and growth hormone was measured after stimulation in these subjects. We recorded the severity of traumatic brain injury, findings from CT scans such as skull fractures, and imaging characteristics of pituitary gland in all the patients by magnetic resonance imaging (MRI). Appropriate statistical analyses, including logistic regression, were utilized to determine the determinants of hypopituitarism. Among the 76 patients, the prevalence of hypopituitarism was 11.84 % in the acute stage and 2.63 % at 24 weeks. Hypopituitarism significantly correlated with injury severity (p < 0.001) and imaging abnormalities observed on MRI. The main imaging findings on MRI were heterogeneous signal intensity, subacute haemorrhage in the anterior pituitary, and reduced pituitary height. A statistically significant decrease was observed in LH (p = 0.009) and FSH levels (p = 0.039) from baseline to 24 weeks. The severity of the injury and the presence of base skull fractures were significantly associated with hypopituitarism (p < 0.001). Our results highlight the importance of checking pituitary function in TBI patients, particularly those with moderate to severe injuries and skull base fractures, to quickly find and treat hormonal deficiencies, which can improve long-term results. Future studies should concentrate on longer follow-up periods and more sophisticated imaging methods to gain a more profound understanding of the mechanisms underlying post-traumatic hypopituitarism.