When ACTH stimulation occurs it might result in the adrenal gland secretion of cortisol and other steroid hormones. ACTH is produced by the pituitary gland and it is released into the petrosal venous sinus in response to stimulation by the corticotrophin releasing hormone(CRH) from the hypothalamus. ACTH is released n the diurnal pattern independent of the circulating cortisol levels. Peak release occurs just before awakening and ACTH levels then decline throughout the day. Control of CRH and ACTH release is maintained through the negative feedback by cortisol at the hypothalamic and pituitary levels. Neuronal input at the hypothalamic level can also stimulate the CRH levels.
The tumours of the cushing’s disease secreate excessive amount of adrenocorticotrophic hormones and results in negative feedback responsiveness to high doses of glucocorticoids. Ectopic sources of ACTH occurs in the form of extracranial neoplasms are generally not responsive to negative feedback with high doses of glucocorticoid. Cushing’s syndrome is classified into ACTH dependent or ACTH independent.
Depression, alcoholism, medications, eating disorders and other conditions can cause mild clinical and laboratory findings, similar to those in Cushing's syndrome, termed “pseudo-Cushing's syndrome.” The laboratory and clinical findings of hypercortisolism disappear if the primary process is successfully treated.
Dexamethasone, an exogenous glucocorticoid, is used to test for Cushing's syndrome. This gluococorticoid does not interfere with cortisol assays but induces similar physiologic responses.