Preface

The initial neuroendocrine response to critical illness illness consists primarily of activated anterior pituitary function, the peripheral anabolic pathways being inactivated. This response presumably provides metabolic substrates, establishes the host's defences and is thus considered to be adaptive and beneficial. It was previously assumed that the acute stress response persisted throughout the course of critical illness, but this assumption has now been disproved. Indeed, a uniformly reduced pulsatile secretion of growth hormone, thyroid-stimulating hormone, prolactin and luteinizing hormone has been observed in protracted critical illness, impairing the function of target organs. A reduced availability of thyrotropin-releasing hormone, gonadotropin-releasing hormone, the endogenous ligand of the growth hormone-releasing peptide receptor (possibly ghrelin) and, in very long-stay critically ill men, also growth hormone-releasing hormone seems to be involved. The pulsatile secretion of growth hormone, thyroid-stimulating hormone, prolactin and luteinizing hormone can be re-established by relevant combinations of releasing factors, which also substantially increase the circulating levels of insulin-like growth factor-1, growth hormone dependent binding proteins, thyroxine, tri-iodothyronine and testosterone. Active feedback inhibition loops prevent the target organs being overstimulated. The metabolism is altered in a beneficial way when growth hormone-secretagogues, thyrotropin-releasing hormone and gonadotropin-releasing hormone are administered together, whereas the effect of single-hormone treatment is minor and accompanied by side-effects. This new concept of a selectively reduced stimulation of pituitary function in the chronic phase of critical illness unveils new therapeutic perspectives to reverse the paradoxical wasting syndrome' and intensive care dependency.