Adrenal Insufficiency and CIRCI

Marik, Paul Ellis

The stress system receives and integrates a diversity of cognitive, emotional, neurosensory, and peripheral somatic signals that are directed to the central nervous system through distinct pathways. The stress response is normally adaptive and time limited and improves the chances of the individual for survival. The stress response is mediated largely by activation of the hypothalamic–pituitary–adrenal (HPA) axis with the release of cortisol. In general, there is a graded cortisol response to the degree of stress, such as the type of surgery. Cortisol levels also correlate with the severity of injury, the Glasgow Coma Scale, and the APACHE score. Cortisol effects the transcription of thousands of genes in every cell of the body. In addition, the cortisol–glucocorticoid receptor complex effects cellular function by non-transcriptional mechanisms. Cortisol has several important physiological actions on metabolism, cardiovascular function, and the immune system. Cortisol increases the synthesis of catecholamines and catecholamine receptors, which are partially responsible for its positive inotropic effects. In addition, cortisol has potent anti-inflammatory actions including the reduction in number and function of various immune cells, such as T and B lymphocytes, monocytes, neutrophils, and eosinophils at sites of inflammation. Cortisol is the most important inhibitor of the transcription of pro-inflammatory mediators (inhibits NF-κB and AP-1 by multiple mechanisms).(1)