New insights into the controversy of adrenal function during XXXX .

@entity1 @entity4545 @entity3124 @entity177 @entity2339 @entity701
UNASSIGNED: @entity3124 represents a life-threatening disorder necessitating recruitment of defence mechanisms for survival. Herein, the @entity2339 is essential. However, the relevance of a relative insufficiency of the @entity2339 in @entity3124 , which is diagnosed by a suppressed @entity701 response to exogenous @entity4545 ( @entity4545 ) irrespective of the plasma @entity701 concentration, is controversial. Findings from several studies have provided insights that clarify at least part of this controversy. Rather than an activated @entity2339 , @entity4545 -independent regulators have been reported to contribute to increased @entity701 availability during @entity3124 . One of these regulators is reduced @entity701 breakdown, mediated by suppressed expression and activity of @entity701 metabolising enzymes in the liver and kidneys. This downstream mechanism increases concentrations of plasma @entity701 , but the ensuing feedback-inhibited @entity4545 release, when sustained for more than 1 week, has been shown to negatively affect adrenocortical integrity and function. Reduced adrenocortical @entity4545 signalling could explain reduced @entity701 responses to exogenous @entity4545 . Whether such reduced @entity701 responses in the presence of raised plasma (free) @entity701 identifies @entity177 needing treatment is unlikely. Additionally, reduced @entity701 breakdown affects the optimum dose of @entity701 treatment during @entity3124 . Identification of @entity1 with an insufficient @entity2339 response and the optimum treatment for this disorder clearly need more well designed preclinical and clinical studies.
