Somatotropic axis dysfunction in critically ill patients: altered response to growth hormone-releasing hormone

Abstract

The aim of this study was to investigate the pituitary‘s capacity to release growth hormone (GH) in critically ill patients by stimulation with GH-releasing hormone (GHRH). Thirty-two patients with severe sepsis and 20 critically ill, nonseptic patients after major surgery were studied in the setting of a surgical intensive care unit. Nine healthy individuals without clinical signs of disturbance of the somatotropic hypothalamic-pituitary axis were included for comparison. The pituitary‘s capacity to release GH was tested with an intravenous bolus injection of 1μg per kg body weight GHRH (Ferring, Kiel, Germany). The median basal plasma GH level was comparable in all groups studied. In contrast, the median peak plasma GH level was significantly lower in critically ill, nonseptic patients after major surgery (5.1, range 1.3–131.0ng/ml, n=20) compared to healthy individuals (23.2, range 12.8–35.2 ng/ml, n=9) (p ;0.01). However, the median peak plasma GH level in patients with severe sepsis (15.3, range 1.6–111.5ng/ml, n=32) was not significantly different compared to healthy individuals (23.2, range 12.8–35.2ng/ml, n=9) (p>>;0.05). The median plasma insulin-like growth factor-I (IGF-I) level was significantly decreased in patients with severe sepsis (32.0, range 32.0–150.0ng/ml, n=32) and in critically, ill, nonseptic patients after major surgery (50.0, range 32.0–144.0ng/ml, n=20) compared to healthy individuals (229.0, range 129.0–503.0ng/ml, n=9) (p ;0.001). No significant difference was found between patients after major surgery and patients with severe sepsis. In conclusion, a low level of circulating IGF-I was associated with the pituitary‘s low capacity to release GH in critically ill, nonseptic patients after major surgery, whereas patients with severe sepsis had a widespread range of pituitary capacity to release GH associated with low IGF-I levels. The pathophysiological basis for not secreting stored GH during critical illness is at present unclear. The treatment with high doses of human GH has been shown to attenuate the catabolic response to injury, surgery and sepsis, whereas in patients with severe sepsis GH administration bypasses its pituitary storage and may trigger a hyperinflammatory response. However, critically ill nonseptic patients after major surgery may profit from GH treatment since they possess a low pituitary capacity to release GH. Thus, performing a GHRH test might facilitate the decision for treatment with human GH.