Hypopituitarism as a consequence of traumatic brain injury (TBI) and its possible relation with cognitive disabilities and mental distress

Abstract

Recent studies have demonstrated that hypopituitarism, in particular GH deficiency, is common among survivors of traumatic brain injury (TBI) tested several months or yr following head trauma. We present the results of endocrine, neurological, neuropsychological and psychiatric evaluation in a group of 67 patients who suffered TBI at least one yr ago. Our study shows that decreased endocrine function is either restricted to one or more anterior pituitary hormones and is present in 34% of patients with any pituitary hormone deficit, while multiple pituitary hormone deficiencies are found in 10% of patients. GH/IGF-I axis was evaluated by GHRH+GHRP-6 test and IGF-I measurement. Severe GHD is the most frequent deficiency present in 15% of TBI patients. Gonadotrophin deficiency was present in 9% of patients with TBI, while thyrotroph and corticotroph function seemed more refractory to impairment. Patients with moderate-to-severe trauma are not necessarily more likely to have hypopituitarism than those with mild injury. Neuropsychological testing revealed a significant positive correlation of peak GH levels after GHRH+GHJRP-6 test with verbal learning and verbal short term memory (RAVLT total score p = 0.06, immediate free recall p = 0.02 and delayed free recall p = 0.04). Verbal and visual memory was significantly lower in elderly patients and in males. Visoconstructional abilities (RCF copy) were significantly lower in the elderly (p < 0.01) and undereducated (p = 0.02). Visual memory (free recall of complex figure after 30 min) significantly correlated with lower IGF-I levels (p = 0.01). Gonadotrophins and testosterone correlated significantly with visoconstructional abilities. Simple and complex conceptual tracking (TMT A and B) was significantly more impaired in older TBI patients (p < 0.01) and with longer time from trauma (TMT B only, p = 0.03). The psychiatric evaluation by using two different scales showed depression, phobic anxiety and psychoticism to be more prominent in the TBI group. Paranoid ideation and somatization negatively correlated with the peak GH responses to GHRH+GHRP-6 test (p = 0.04 and p = 0.03, respectively). Depression scale showed that nearly half of patients suffered from mild to moderate depression. The benefits of hormone replacement therapy on cognitive functioning and mental distress in TBI patients are eagerly awaited.

Should anterior pituitary function be tested during follow-up of all patients presenting at the emergency department because of traumatic brain injury?

“…In these previous studies (5,(7)(8)(9)(10)(11)(12)(13)(14), the percentage of patients with Mod/STBI was higher (56-100%) than that of the patients in our study. In addition to the differences in the study cohorts, the wide range of reported prevalences of hypopituitarism (varying from 15 to 56%) may be attributed to the differences in diagnostic criteria (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Furthermore, some studies included patients in whom, besides a history of TBI, alternative causes of pituitary dysfunction had not been ruled out, such as pre-existent hypopituitarism (6-10, 12, 14), BMI above 30 kg/m 2 (5-10, 12-14), and substance abuse (6-10, 12).…”

“…In all the 30 patients with Mod/STBI participating in our study, anterior pituitary function was normal. The prevalence of hypopituitarism after TBI that we report is considerably lower than the prevalences reported by recent studies (15-56%) (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The aim of our study was to evaluate anterior pituitary function in a patient cohort representative for all the patients with TBI.…”

“…O5 months after TBI. Some authors did not unequivocally specify the population from which the study population was selected, or did not unequivocally define the selection criteria (6,10,12,13). Consequently, the population in which the prevalence of pituitary dysfunction was assessed remained insufficiently defined.…”

“…Consequently, the population in which the prevalence of pituitary dysfunction was assessed remained insufficiently defined. Contrary to our study, patients who were evaluated in all previous studies were selected from hospitalized patient populations only (at a general ward (5,7,8,10,13,14), at an ICU (9,12), or at a rehabilitation institute (11)). Therefore, these studies included patients with more severe brain injury.…”

“…Involvement of the posterior pituitary gland during the acute phase after severe head trauma has been acknowledged for years, but trauma-induced anterior pituitary dysfunction was considered rare (4). However, several recent studies have reported of a high frequency of anterior pituitary hormone insufficiency between 2 weeks and 1.5 years after TBI, varying from 15 to 56% of patients with moderate or severe TBI (Mod/STBI) (5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”