Long-term neuroendocrine consequences of traumatic brain injury and strategies for management

ABSTRACT

Introduction: Traumatic brain injuries (TBI) are reported to cause neuroendocrine impairment with a prevalence of 15% with confirmatory testing. Pituitary dysfunction (PD) may have detrimental effects on vital parameters as well as on body composition, cardiovascular functions, cognition, and quality of life. Therefore, much effort has been made to identify predictive factors for post-TBI PD and various screening strategies have been offered.

Areas covered: We searched PubMed and reviewed the recent data on clinical perspectives and long-term outcomes as well as predictive factors and screening modalities of post-TBI PD. Inconsistencies in the literature are overviewed and new areas of research are discussed.

Expert opinion: Studies investigating biomarkers that will accurately predict TBI patients with a high risk of PD are generally pilot studies with a small number of participants. Anti-pituitary and anti-hypothalamic antibodies, neural proteins, micro-RNAs are promising in this field. As severity of TBI has been the most commonly associated risk factor for post-TBI PD, we suggest prospective screening based on severity of head trauma until new evidence emerges. There is also a need for more studies investigating the clinical effects of hormone replacement in TBI patients with PD.

KEYWORDS:

• Biomarkers
• hypopituitarism
• pituitary dysfunction
• posterior pituitary
• traumatic brain injury

Article Highlights

• The prevalence of post-TBI pituitary dysfunction varies greatly across studies because of different diagnostic methods performed at different time points after TBI and with various study populations in terms of age, gender, BMI, and severity of the trauma.

• Direct injuries to the pituitary gland and hypothalamus or secondary insults may lead to transient or permanent pituitary dysfunction. Autoimmunity and genetic polymorphisms of certain genes may also be involved in pathophysiology.

• Many risk factors for neuroendocrine impairment have been investigated but there are inconsistent results. There is a need for large clinical trials to determine biomarkers that can accurately predict patients at risk.

• Patients with post-TBI pituitary dysfunction may suffer from life-threatening conditions such as hypotension during the acute phase or may have non-specific complaints such as fatigue and depression during the chronic phase.

• Generally, the authors did not suggest screening patients with low life expectancy and patients with mild TBI, who did not have any additional risk factors and did not need hospitalization. However, screening of patients with ‘complicated mild TBI’ was reported to be useful as most of the mild TBIs that caused PD were in fact ‘complicated mild TBIs.’ In addition, patients with moderate or severe TBI were recommended for screening of the development of hormone deficiencies.

• The replacement modalities of pituitary dysfunction during long-term is not different for patients with TBI but clinicians should keep in mind the possibility of recovery of hormone deficiencies. Growth hormone replacement is not recommended until 1-year post-TBI.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.