Pituitaryadrenal axis

It has been known for a long time that the vital stress-induced hypercortisolism induced by surgery, trauma or sepsis is associated with augmented adrenocorticotropic hormone (ACTH) release, driven presumably by corticotropin-releasing hormone (CRH), cytokines and the noradrenergic system. Concomitantly, circulating aldosterone rises markedly probably under the control of an activated renin-angiotensin system. Hypercortisolism acutely shifts carbohydrate, fat and protein metabolism, so that energy is instantly and selectively available to vital organs such as the brain and so that anabolism is delayed.

In PCI serum ACTH levels are low, while cortisol levels remain elevated, indicating that cortisol release may in this phase be driven through an alternative pathway possibly involving endothelin (Vermes et al 1995). The mechanism responsible for low ACTH levels in PCI is unknown although a role for atrial natriuretic peptide or substance P has been suggested. In contrast, circulating levels of adrenal androgens such as dehydroepiandrosterone sulfate (DHEAS) (Van den Berghe et al 1995) and the mineralocorticoid, aldosterone, are reduced, despite increased renin activity (Zipser et al 1981) in PCI. This steroid profile suggests a shift of pregnenolone metabolism away from both mineralocorticoid and adrenal androgen pathways towards the glucocorticoid pathway. The mechanism responsible for this change in steroid secretory pattern is unknown but ultimately it may fail thereby accounting for the 20-fold higher incidence of adrenal insufficiency in critically ill patients over the age of 50 years and being treated on the intensive care unit for more than 14 days. The fact that this type of relative adrenal failure coincides with adverse outcomes suggests that high levels of glucocorticoids remain essential for haemodynamic stability. Whether hypercortisolium in the chronic phase of critical illness is exclusively beneficial remains uncertain.

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