In the blood the amounts of cortisol and corticosterone, another adrenal hormone, are monitored by the hypothalamus, a regulatory organ located at the forebrain. Low levels of these substances induce secretion of a releasing hormone, CRF (corticotropin-releasing factor), which acts upon the anterior pituitary, causing the release of ACTH ( adrenocorticotropic hormone). ACTH controls the secretion of cortisol from the adrenal cortex. High cortisol levels inhibit CRF-induced ACTH release. Cortisol is rapidly metabolized to several products that are excreted in the urine.

Use of cortisol in therapy produces the same undesirable side effects as cortisone. Both drugs have been largely superseded by such synthetic steroids as prednisolone.