Measurement of the glucocorticoid receptor: Relevance to the diagnosis of critical illness-related corticosteroid insufficiency in children

Diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in children continues to remain difficult and controversial in that no consensus for either exists among pediatric critical care physicians. Critical illness-related corticosteroid insufficiency is defined as a corticosteroid response that is inadequate for the severity of the illness experienced by the patient. Critical illness-related corticosteroid insufficiency manifests as an insufficient corticosteroid mediated down-regulation of proinflammatory cytokines, due to either corticosteroid tissue resistance and/or inadequate circulating levels of cortisol. The tissue resistance is likely due to alterations in the functionality of the intracellular receptor for corticosteroids, the glucocorticoid receptor (GR). This article details the role of the GR during critical illness with a focus upon the measurement of the GR, as a potentially important means by which to clinically assess the level of corticosteroid tissue-resistant in patients suspected of CIRCI. Measurement of the GR may be particularly useful as a means by which to determine the judicious administration of steroids, maximizing their therapeutic potential, whereas minimizing the morbidity that can be associated with their use.