Neuroendocrine pathobiology of chronic critical illness.
The neuroendocrine stress response is a dynamic process involving multiple hormonal alterations with distinct features in the acute and chronic phase of critical illness. In the initial response to an acute stress event, the anterior pituitary actively releases its hormones into the circulation while in the periphery, anabolic target organ hormones are inactivated. This response is thought to be beneficial and adaptive. When critical illness becomes prolonged, pulsatile secretion of anterior pituitary hormones becomes uniformly reduced due to reduced (hypothalamic) stimulation, and this underlies reduced activity of the respective target tissues and impaired anabolism. This difference in the acute and chronic stress response may not be trivial. It was the (inappropriate) assumption that acute stress responses, such as GH resistance, persist throughout the course of critical illness, which had formed the (inappropriate) justification to administer high doses of GH to long-stay intensive care patients to induce anabolism [102]. The concomitant endocrine changes in chronic critical illness may have predisposed to severe side effects of high doses of GH. In view of the significant benefits of strict glycemic control using exogenous insulin recently demonstrated in ICU patients [101], GH-induced insulin resistance and hyperglycemia may have played a role. It remains to be studied whether endocrine intervention with releasing factors such as TRH and GHRP in prolonged critical illness will accelerate recovery of patients who have entered the vicious circle of prolonged intensive care dependency.
Van den Berghe
Greet
G
Department of Intensive Care Medicine, University Hospital Gasthuisberg, Catholic University of Leuven, B-3000 Leuven, Belgium. greta.vandenberghe@med.kuleuven.ac.be
D002908:Chronic Disease; D016638:Critical Illness; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D009490:Neurosecretory Systems / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D013961:Thyroid Gland / Q000503:physiopathology; D013963:Thyroid Hormones / Q000378:metabolism
D013963:Thyroid Hormones; D013007:Growth Hormone-Releasing Hormone