At times of stress or after major traumatic injury, the hypothalamic-pituitary-adrenal axis provides an important mechanism to support the body through diurnal rhythms. The hypothalamus releases corticotropin-releasing factor, which stimulates the anterior pituitary gland to produce adrenocorticotropic hormone (ACTH). The ACTH then stimulates the cortex of the adrenal gland to release glucocorticoids and mineralocorticoids. Glucocorticoids primarily affect carbohydrate and protein metabolism. These chemicals include cortisol, cortisone, and hydrocortisone. Mineralocorticoids primarily affect sodium and water metabolism.

Mineralocorticoids lead to the retention of sodium and secretion of potassium. In addition, calcium, phosphorous, and bicarbonate are also reabsorbed. These actions are primarily mediated by the reninangiotensin-aldosterone system. Angiotensin 2 produced by this system leads to aldosterone production, which is a naturally occurring mineralocorticoid. Fludrocortisone is the pharmacological form of mineralocorticoids and is used to provide mineralocorticoid effects in conditions like syncope, orthostatic hypotension, and Addison disease.