The term "cortisone" is frequently misused to mean either any corticosteroid or hydrocortisone, which is in fact cortisol. Many who speak of receiving a "cortisone shot" or taking "cortisone" are more likely receiving hydrocortisone or one of many other, much more potent synthetic corticosteroids.
Cortisone can be administered as a prodrug, meaning it has to be converted by the body (specifically the liver, converting it into cortisol) after administration to be effective. It is used to treat a variety of ailments and can be administered intravenously, orally, intra-articularly (into a joint), or transcutaneously. Cortisone suppresses various elements of the immune system, thus reducing inflammation and attendant pain and swelling. Risks exist, in particular in the long-term use of cortisone.[1][2] However, using cortisone only results in very mild activity, and very often more potent steroids are used instead.
Effects and uses
Cortisone itself is inactive.[3] It must be converted to cortisol by the action of 11β-hydroxysteroid dehydrogenase type 1.[4] This primarily happens in the liver, the main site at which cortisone becomes cortisol after oral or systemic injection, and can thus have a pharmacological effect. After application to the skin or injection into a joint, local cells that express 11β-hydroxysteroid dehydrogenase type 1 instead convert it to active cortisol.
Cortisone was first identified by the American chemists Edward Calvin Kendall and Harold L. Mason while researching at the Mayo Clinic.[10][11][12] During the discovery process, cortisone was known as compound E (while cortisol was known as compound F).
In 1949, Philip S. Hench and colleagues discovered that large doses of injected cortisone were effective in the treatment of patients with severe rheumatoid arthritis.[13] Kendall was awarded the 1950 Nobel Prize for Physiology or Medicine along with Philip Showalter Hench and Tadeusz Reichstein for the discovery of the structure and function of adrenal cortex hormones including cortisone.[14][15] Both Reichstein and the team of O. Wintersteiner and J. Pfiffner had separately isolated the compound prior to the discovery made by Mason and Kendall, but failed to recognize its biological significance.[11] Mason's contributions to the crystallization and characterization of the compound have generally been forgotten outside of the Mayo Clinic.[11]
Cortisone is one of several end-products of a process called steroidogenesis. This process starts with the synthesis of cholesterol, which then proceeds through a series of modifications in the adrenal gland to become any one of many steroid hormones. One end-product of this pathway is cortisol. For cortisol to be released from the adrenal gland, a cascade of signaling occurs. Corticotropin-releasing hormone released from the hypothalamus stimulates corticotrophs in the anterior pituitary to release ACTH, which relays the signal to the adrenal cortex. Here, the zona fasciculata and zona reticularis, in response to ACTH, secrete glucocorticoids, in particular cortisol. In various peripheral tissues, notably the kidneys, cortisol is inactivated to cortisone by the enzymecorticosteroid 11-beta-dehydrogenase isozyme 2. This is crucial because cortisol is a potent mineralocorticoid and would cause havoc with electrolyte levels (raising blood sodium and lowering blood potassium levels) and raise blood pressure if it were not inactivated in the kidneys.[4]
Because cortisone must be converted to cortisol before being active as a glucocorticoid, its activity is less than simply administering cortisol directly (80–90%).[19]
Popular culture
Abuse and addiction to cortisone was the subject of the 1956 motion picture Bigger Than Life, produced by and starring James Mason. Though it was a box-office flop upon its initial release,[20] many modern critics hail the film as a masterpiece and brilliant indictment of contemporary attitudes toward mental illness and addiction.[21] In 1963, Jean-Luc Godard named it one of the ten greatest American sound films ever made.[22]
^Gibbons, Ray (1949). "Science gets synthetic key to rare drug; discovery is made in Chicago". Chicago Tribune. Chicago. p. 1.
^Quirke, Viviane (2005). "Making British Cortisone: Glaxo and the development of Corticosteroids in Britain in the 1950s–1960s". Studies in History and Philosophy of Science Part C. 36 (4): 645–674. doi:10.1016/j.shpsc.2005.09.001. PMID16337555.
Woodward R. B.; Sondheimer F.; Taub D. (1951). "The Total Synthesis of Cortisone". Journal of the American Chemical Society. 73 (8): 4057. Bibcode:1951JAChS..73.4057W. doi:10.1021/ja01152a551.
