GH Deficiency as The Most Common Pituitary Defect After TBI: Clinical Implications

Abstract

Recent studies have demonstrated that hypopituitarism, and in particular growth hormone deficiency (GHD), is common among survivors of traumatic brain injury (TBI) tested several months or years following head trauma. In addition, it has been shown that post-traumatic neuroendocrine abnormalities occur early and with high frequency. These findings may have significant implications for the recovery and rehabilitation of patients with TBI. The subjects at risk are those who have suffered moderate-to severe head trauma although mild intensity trauma may precede hypopituitarism also. Particular attention should be paid to this problem in children and adolescents. GH deficiency is very common in TBI, particularly isolated GHD. For the assessment of the GH-IGF axis in TBI patients, plasma IGF-I concentrations plus GH response to a provocative test is mandatory. Growth retardation secondary to GHD is a predominant feature of GHD after TBI in children. Clinical features of adult GHD are variable and in most obesity is present. Neuropsychological examinations of patients with TBI show that a significant portion of variables like attention, concentration, learning, memory, conceptual thinking, problem solving and language are impaired in patients with TBI. In the few case reports described, hormone replacement therapy in hormone deficient head-injured patients resulted in major neurobehavioral improvements. Improvements in mental-well being and cognitive function with GH replacement therapy in GHD adults have been reported. The effect of GH replacement in posttraumatic GHD needs to be examined in randomized controlled studies.

Investigation of antihypothalamus and antipituitary antibodies in amateur boxers: is chronic repetitive head trauma-induced pituitary dysfunction associated with autoimmunity?

“…The possible mechanisms of the activation of the hypothalamic-pituitary autoimmunity after TBI or boxing remain to be clarified. Generally, in patients after moderate and severe TBI, necrotic, ischemic, and hypoxic changes could be present not only at the pituitary level but also at the hypothalamic level (2, 28); GH-GHRH and corticotropin-releasing hormone (CRH) neurons could be highly vulnerable to injury in these cases (28,29). With this in mind, it is tempting to speculate that head trauma may trigger an ongoing cascade of vascular and histopathological alterations involving mediators of inflammatory process, thus favoring the immune system activation which can contribute to late pituitary dysfunction.…”

Antipituitary antibodies after traumatic brain injury: is head trauma-induced pituitary dysfunction associated with autoimmunity?

“…The presence of selective hypopituitarism in the two APA-negative patients requires a discussion. Generally, in patients after moderate and severe TBI, necrotic, ischemic, and hypoxic changes could be present not only at pituitary but also at hypothalamic level (2,24); GHRH and corticotrophin-releasing hormone neurons could be highly vulnerable to injury in these cases (24,25). With this in mind, it is tempting to speculate that head trauma may trigger an ongoing cascade of vascular and histopathological alterations involving mediators of inflammatory process, thus favoring the immune system activation that can contribute to late pituitary dysfunction.…”

“…Inflammatory mediators (cytokines, in particular interleukin (IL)6, free radicals, amino acids, and nitric oxide) may lead to accelerated neuronal-cell necrosis (27,29). The infundibular hypothalamic-pituitary structure due to its peculiar anatomical and vascular characteristics may be very vulnerable to these necrotic, ischemic, and hypoxic changes present after TBI (25). In contrast to present findings, APAs were found to be negative in pituitary damage secondary to surgery for pituitary and parasellar tumors (9).…”

Neurobehavioral sequelae of traumatic brain injury

“…43 Hypopituitarism, with resultant neuroendocrine abnormalities such as growth hormone deficiency and cortisol deficiency, may also be associated with post-TBI fatigue. 47 Other possible contributing factors include vertigo, diplopia, and iatrogenic causes, such as psychotropic or analgesic medications.…”