Growth Hormone Deficiency Following Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is fairly common and annually affects millions of people worldwide. Post traumatic hypopituitarism (PTHP) has been increasingly recognized as an important and prevalent clinical entity. Growth hormone deficiency (GHD) is the most common pituitary hormone deficit in long-term survivors of TBI. The pathophysiology of GHD post TBI is thought to be multifactorial including primary and secondary mechanisms. An interplay of ischemia, cytotoxicity, and inflammation post TBI have been suggested, resulting in pituitary hormone deficits. Signs and symptoms of GHD can overlap with those of TBI and may delay rehabilitation/recovery if not recognized and treated. Screening for GHD is recommended in the chronic phase, at least six months to a year after TBI as GH may recover in those with GHD in the acute phase; conversely, it may manifest in those with a previously intact GH axis. Dynamic testing is the standard method to diagnose GHD in this population. GHD is associated with long-term poor medical outcomes. Treatment with recombinant human growth hormone (rhGH) seems to ameliorate some of these features. This review will discuss the frequency and pathophysiology of GHD post TBI, its clinical consequences, and the outcomes of treatment with GH replacement.

Impact of Pituitary Autoimmunity and Genetic Disorders on Growth Hormone Deficiency in Children and Adults

“…The most frequent causes of traumatic brain injury (TBI) are road accidents (the main cause, which represents 50% of all cases) followed by falls, accidents related to violence, head injury linked to sport (hockey, football, soccer), combat sports (boxing and kickboxing) characterized by chronic repetitive head injuries and accidental war trauma, including explosion lesions [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. Posttraumatic hypopituitarism is generally characterized by an isolated anterior pituitary hormone Immunofluorescence in cryostat sections of young baboon anterior pituitary gland tested against the serum of a patient with isolated growth hormone deficiency GHD, in a primary step adding FITC goat sera anti-human immunoglobulins (left panel: (a) = simple immunofluorescence) and in a second immunostaining step adding rabbit antisera anti-GH followed by rhodamine goat sera anti rabbit IgG (right panel: (b) = double four-layer immunofluorescence).…”

“…Post-traumatic hypopituitarism is generally characterized by an isolated anterior pituitary hormone deficiency rather than multiple hormone deficiencies. Impairment of GH secretion and consequently of IGF-1 concentrations seems to be the most common early disorder after traumatic brain injury, both in the acute and chronic phase [25,29]. Concerning this, it has been suggested that impairment of GH and gonadotropin secretions is the most commonly pituitary disorder occurring post-TBI due to the more lateral location of somatotrophs and gonadotrophs at a pituitary level [25,26].…”

Traumatic Brain Injury as Frequent Cause of Hypopituitarism and Growth Hormone Deficiency: Epidemiology, Diagnosis, and Treatment

“…Patients with post-TBI GHD have a higher risk to achieve poor cognition outcomes than those with an intact somatotropic axis after trauma ( 87 ). Park et al showed that patients with GHD after TBI have decreased cerebral glucose metabolism in specific cortical areas involved in intellectual function, executive function, and working memory ( 88 ).…”

“…PTHP, and in particular GHD, are often underdiagnosed: patients with post-TBI GHD seem to be diagnosed on average two and a half years later after the primary onset of disease when compared to those with Non-Functioning Pituitary Adenoma (NFPA) ( 87 ).…”

“…A rational approach is to evaluate life expectancy, avoiding to test patients with poor prognosis who cannot benefit of hormonal replacement therapy. Conversely, patients with mild TBI could develop hypopituitarism, but not all of them achieve medical attention ( 90 ) and testing is not considered cost-effective ( 87 ).…”