Growth hormone secretagogues in critical illness

Alterations within the somatotropic axis occurring during the course of cri tical illness follow a biphasic pattern. The initial stress response consis ts of activated growth hormone (GH) release whereas circulating levels of G H-dependent insulin-like growth factor (IGF)-I and IGF binding protein (IGF BP)-3 fall and IGFBP-1 concentrations rise. In contrast, in the chronic int ensive care-dependent phase of severe illness, pulsatile GH secretion subst antially decreases whereas the non-pulsatile fraction remains relatively el evated, resulting in an abnormally flat GH secretory pattern and low-normal mean nocturnal GH serum concentrations. Specifically the reduced amount of GH released in pulses is found to be related to low circulating levels of IGF-I, IGFBP-3 and acid-labile subunit (ALS), which suggests that a relativ e hyposomatotropism may participate in the pathogenesis of the wasting synd rome distinctively in the chronic phase of critical illness. The relative h yposomatotropism seems at least in part of hypothalamic origin since the wh ole somatotropic axis has been found to be very responsive to continuous in fusion of GH releasing peptide (GHRP), administered alone or in combination with GH releasing hormone (GHRH), as evidenced by reactivated pulsatile GH secretion followed by substantial increases in circulating levels of IGF-I , IGFBP-3 and ALS. GHRH alone, however, is unable to exert the same effect, which may point to an underlying reduced availability of the endogenous li gand for the GHRP receptor. The presence of considerable responsiveness to restored endogenous pulsatile GH secretion using GHRPs not only further del ineates the distinct pathophysiological paradigm of the chronic phase of cr itical illness, as opposed to the acute phase, which is thought to be prima rily a condition of GH resistance, but may also have important therapeutic consequences. Recent data revealed that this novel strategy evokes metaboli c improvement related to the balanced endocrine responses. Whether GH secre tagogues also enhance clinical recovery of protracted critically ill patien ts remains to be elucidated. Copyright (C) 1999 S. Karger AG, Basel.