Despite feeding, lean tissue is wasted during critical illness, a problem that often persists even after the underlying disease has resolved and that perpetuates intensive care dependency. A neuroendocrine dysfunction in the chronic phase of illness was recently found to play a role.
The acute phase of critical illness consists primarily of an activated anterior pituitary function, whereas peripheral anabolic pathways are inactivated. It provides the metabolic substrates and host defense required for survival and thus has been considered adaptive and beneficial. Persistence of this acute stress response throughout the course of critical illness was hitherto assumed. This assumption has now been invalidated. Indeed, a uniformly reduced pulsatile secretion of several anterior pituitary hormones is present in protracted critical illness, causing impaired function of target organs. A hypothalamic rather than pituitary dysfunction explains why administration of relevant releasing factors evokes immediate and pronounced pituitary hormone release followed by increases of target organ hormone levels and peripheral tissue responses. Recognizing the differences between acute and prolonged critical illness offers a frame in which to interpret recent “unexpected” adverse outcomes of studies using high doses of either thyroxine or growth hormone in long-stay intensive care unit patients. Also, the new concept of reduced stimulation of pituitary function in protracted critical illness opens new therapeutic perspectives to reverse the paradoxical ‘wasting syndrome’ and intensive care dependency. Treatment with releasing factors, as opposed to peripherally active hormones such as thyroid hormone, growth hormone, insulin-like growth factor-I, or anabolic steroids, enables the body to adjust peripheral hormonal metabolism and activity according to the needs determined by the disease process. This is an important safety aspect for an endocrine treatment at a time when it is virtually impossible to determine ‘normal’ or ‘optimal’ circulating levels of different peripherally active hormones. Whether this novel endocrine strategy will also enhance clinical recovery from critical illness remains to be explored.
Catholic University of Leuven, School of Medicine, Leuven, Belgium.
Correspondence to Greet Van den Berghe, MD, PhD, Department of Intensive Care Medicine, University Hospital Gasthuisberg, University of Leuven, B-3000 Leuven, Belgium; e-mail: email@example.com