These factors include preexisting conditions that affect the HPA axis; however, corticosteroid insufficiency during the course of acute illness can also be due to abnormal responses to corticotropin-releasing hormone and corticotropin induced by head injuries, central nervous system depressants, or pituitary infarction; adrenal hemorrhage caused by septicemia and underlying coagulopathy; extensive destruction of adrenal tissues caused by tumors or infections; and direct inhibition of adrenal cortisol synthesis caused by high levels of inflammatory cytokines in patients with sepsis [35]. Here, CRH is linked to infection.