The cause of Cushing syndrome (endogenous hypercortisolism rather than exogenous hypercortisolism resulting from medication) is overproduction of cortisol due to either a primary adrenal disease (eg, adenoma, carcinoma, nodular hyperplasia) or an excess of corticotropin (from a pituitary tumor or an ectopic source). The most frequently diagnosed subtype of hypercortisolism is corticotropin-dependent Cushing disease resulting from a pituitary corticotroph adenoma. It most commonly occurs in women in the third to fifth decades of life. Insidious in onset, it usually occurs 2-5 years before a clinical diagnosis is made.
When activated macrophages start to secrete IL-1, which synergistically with CRH increases ACTH,  T-cells also secrete glucosteroid response modifying factor (GRMF), as well as IL-1; both increase the amount of cortisol required to inhibit almost all the immune cells.  Immune cells then assume their own regulation, but at a higher cortisol setpoint. The increase in cortisol in diarrheic calves is minimal over healthy calves, however, and falls over time.  The cells do not lose all their fight-or-flight override because of interleukin-1's synergism with CRH. Cortisol even has a negative feedback effect on interleukin-1  —especially useful to treat diseases that force the hypothalamus to secrete too much CRH, such as those caused by endotoxic bacteria. The suppressor immune cells are not affected by GRMF,  so the immune cells' effective setpoint may be even higher than the setpoint for physiological processes. GRMF affects primarily the liver (rather than the kidneys) for some physiological processes.