Novel insights in the neuroendocrinology of critical illness

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Novel insights in the neuroendocrinology of critical illness

Greet Van den Berghe

Department of Intensive Care Medicine, University Hospital

Gasthuisberg, Catholic University of Leuven, B-3000 Leuven, Belgium

(Correspondence should be addressed to G Van den Berghe)

Abstract

An unexplained hallmark of prolonged critical illness is the

inability of feeding to prevent or reverse protein wasting while fat

is paradoxically accrued. This `wasting syndrome' often

persists

after the underlying disease has resolved and thus perpetuates

intensive care dependency.

Although the crucial role of an intact hypothalamus-pituitary axis

for homeostasis during stress is well recognized, the differences

between the neuroendocrine changes observed in acute and prolonged

critical illness were only recently described.

Novel insights in this area are here reviewed.

The initial endocrine stress response consists primarily of a

peripheral inactivation of anabolic pathways while pituitary activity

is essentially amplified or maintained.

These responses presumably provide metabolic substrates and host

defense required for survival and delay anabolism, thus to be

considered as adaptive and beneficial.

Persistence of this acute stress response throughout the course of

critical illness was hitherto assumed.

This assumption has now been invalidated, since a uniformly reduced

pulsatile secretion of ACTH, TSH, LH, PRL and GH has been observed in

protracted critical illness whereby diminished stimulation of several

target organs.

Impaired pulsatile secretion of anterior pituitary hormones in the

chronic phase of critical illness seems to have a hypothalamic rather

than pituitary origin, as administration of relevant releasing

factors evoked immediate and pronounced pituitary hormone release.

A reduced availability of TRH, one of the endogenous ligands of the

GHRP receptor (such as the recently discovered ghrelin) and, in very

long-stay critically ill men also of GHRH, appear to be involved.

This hypothesis was further explored by investigating the effects of

continuous IV infusion of GHRH, GHRP, TRH and their combinations for

several days.

Pulsatile secretion of GH, TSH and PRL was re-amplified by relevant

combinations of releasing factors which also substantially increased

circulating levels of IGF-I, GH-dependent binding proteins, T4, and

T3 while avoiding a rise in reverse T3.

Active feedback inhibition loops prevented overstimulation of target

organs and metabolic improvement was noted with the combined infusion

of GHRP and TRH.

Whether this novel endocrine strategy will also enhance clinical

recovery from critical illness remains to be explored.

European Journal of Endocrinology

July 2000