We hypothesized that sepsis-induced critical illness, further referred to as ‘sepsis,’ indeed immediately and continuously activates the hypothalamus to generate, via CRH and AVP, ACTH-induced hypercortisolism, but as soon as free cortisol is elevated, feedback inhibition at the pituitary level interferes with normal processing of POMC into ACTH, explaining the typical ACTH–cortisol dissociation. This evidence concerns the gene POMC and adrenal gland hyperfunction.