Dynamic neuroendocrine responses to critical illness

Abstract

Prolonged critical illness has high morbidity and mortality. The acute neuroendocrine response to critical illness involves an activated anterior pituitary function. In prolonged critical illness, however, a reduced pulsatile secretion of anterior pituitary hormones and the so-called 'wasting syndrome' occur. The impaired pulsatile secretion of growth hormone (GH), thyrotropin and gonadotropin can be re-amplified by relevant combinations of releasing factors, which also substantially increase circulating levels of insulin-like growth factor (IGF)-I, GH-dependent IGF-binding proteins, thyroxine, tri-iodothyronine, and testosterone. Anabolism is clearly re-initiated when GH secretagogues, thyrotropin-releasing and gonadotropin-releasing hormones are co-administered but the effect on survival remains unknown. A lethal outcome of critical illness is predicted by a high serum concentration of IGF-binding protein 1, pointing to impaired insulin effect rather than pituitary function, and survival was recently shown to be dramatically improved by strict normalization of glycemia with exogenous insulin. The recent progress in the knowledge of the neuroendocrine response to critical illness and its interrelation with peripheral hormonal and metabolic alterations during stress allows for potential new therapeutic perspectives to safely reverse the wasting syndrome and improve survival. These novel insights will be reviewed herein.