Progress in understanding of adrenal insufficiency in septic patients

Abstract

Background Sepsis is one of the critical complications following serious injuries or major surgeries. It is a leading cause of death. The mortality of septic shock exceeds 40%. Accumulating studies have demonstrated that the severity of adrenal cortex dysfunction has a vital impact on the phenotype and prognosis of sepsis, while glucocorticoid(GC) may be an effective intervention. However, the mechanisms underlying adrenocortical dysfunction remain unclear. Objective To review strategies for assessment of adrenocortical function, and timely supplement of GC, aiming to appropriately compensate the impaired adrenal function, finally, to improve prognosis and to reduce mortality of sepsis. Content At the early stage of sepsis, hypothalamus-pituitary-adrenal axis(H-P-A) is activated, and is followed by release of GC and mobilization of inflammation cascades, especially mitogen-activated protein kinase(MAPK) and nuclear regulatory factor-κB pathways. GC counteracts the inflammation cascades. At the late stage of sepsis or during sepsis shock, damages of adrenocortical cells and vascular epithelia cells occur in adrenal gland, resulting in adrenocortical dysfunction, including low levels of GC and low affinity of GC receptors. The measurement of serum GC and adrenocorticotrophic hormone are combined to assess adrenocortical function: adrenal insufficiency(AI) or relative adrenal insufficiency(RAI). Low doses of GC help to reverse septic shock, improve adrenal function, and maintain normal hemodynamics in septic patients. Trend Further investigation in understanding the mechanisms underlying AI and RAI are highly demanded to optimize therapeutic application of GC in sepsis. Key words: Sepsis; Septic shock; Adrenal insufficiency; Relative adrenal insufficiency