Evidence for integrity of the growth hormone/insulin-like growth factor-1 axis in patients with severe head trauma during rehabilitation

Abstract

Severe traumatic head injury has been recognized to be associated with hypothalamo-hypophyseal impairment and subsequent abnormalities in hormone secretion, which can contribute to a prolonged clinical course and to hampered recovery in many head-injured patients. Most of the data on the growth hormone/insulin-like growth factor -1 (GH/IGF-1) axis function have been obtained early after head injury, whereas GH secretory pattern has not been fully elucidated after patients had left the intensive care unit. We examined the activity of the GH/IGF-1 axis in 16 severely closed head-injured (CHI) patients (14 males; age range, 17 to 47 years; body mass index [BMI], 21.4 [plusmn] 0.8 kg/m 2) during the rehabilitation period at least 1 month after leaving the intensive care unit and in 12 sex-, age-, and weight-matched healthy controls. The severity of trauma was assessed by the Glasgow Coma Scale (GCS) score (8 or less), posttraumatic amnesia (PTA, more than 24 hours), and initial computed tomography (CT) scan. The clinical picture at time of the study was evaluated by the Rancho Los Amigos Scale of Cognitive Functioning (CFS) and the Functional Independence Measure (FIM). In all subjects, we evaluated basal levels of anterior pituitary hormones, IGF-1, insulin-like growth factor-binding protein (IGFBP)-3, and IGFBP-1, as well as the GH responses to intravenous (IV) infusion of growth hormone-releasing hormone (GHRH) alone, GHRH plus arginine (ARG), and the GH release evoked by somatostatin (SRIH) infusion withdrawal, which is related to endogenous GHRH tone. In all subjects, nutritional parameters and nitrogen balance were normal. Basal plasma concentrations of GH, IGF-1, IGFBP-3, and IGFBP-1 did not significantly differ between CHI patients and controls. The GH responses to GHRH and GHRH plus ARG did not significantly differ between CHI patients (GH peak, 10.7 [plusmn] 3.0 [mu ]g/L; area under the curve [AUC], 5.9 [plusmn] 1.5 [mu ]g/L [middot] min; and GH peak, 34.7 [plusmn] 6.1 [mu ]g/L; AUC, 20.25 [plusmn] 3.3 [mu ]g/L [middot] min, respectively) and normal subjects (GH peak at 30 minutes, 7.23 [plusmn] 1.35 [mu ]g/L; AUC, 4.7 [plusmn] 0.8 [mu ]g/L [middot] min; and GH peak at 60 minutes, 41.0 [plusmn] 5.1 [mu ]g/L; AUC, 24.3 [plusmn] 1.7 [mu ]g/L [middot] min, respectively). SRIH withdrawal resulted in an unequivocal increase in plasma GH concentrations both in CHI patients and in controls, without any significant difference between the 2 groups. A negative correlation was found between the GH response ([Delta ]GH peak) to SRIH withdrawal and CFS ( r = [minus ].615, P [lt ] .005). In conclusion, our study indicates that patients receiving rehabilitation after leaving the intensive care unit for severe traumatic head injury have no significant changes of GH secretion with normal central regulation of the GH-IGF-1 axis.