Cortisone is a

pregnene A pregnene is an alkene derivative of a pregnane. An example is cortisone. Image:Cortison.svg, Cortisone Image:Ethisterone.png, Ethisterone Image:Spironolacton.svg, Spironolactone References See also * Pregnanes Pregnane, also known as 1 ...

(21-carbon) steroid hormone. It is a naturally-occurring

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are inv ...

metabolite that is also used as a pharmaceutical

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the dru ...

; it is not synthesized in the adrenal glands.

Cortisol Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the '' zona fasciculata'' of the adrenal cortex in the adrenal g ...

is converted by the action of the enzyme corticosteroid 11-beta-dehydrogenase isozyme 2 into the inactive metabolite cortisone, particularly in the kidneys. Cortisone is converted back to the active steroid cortisol by the action of the enzyme

11β-Hydroxysteroid dehydrogenase type 1 11β-Hydroxysteroid dehydrogenase type 1, also known as cortisone reductase, is an NADPH-dependent enzyme highly expressed in key metabolic tissues including liver, adipose tissue, and the central nervous system. In these tissues, HSD11B1 redu ...

, particularly in the liver. The term "cortisone" is frequently misused to mean either any

or hydrocortisone, which is actually another name for

cortisol Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the '' zona fasciculata'' of the adrenal cortex in the adrenal g ...

. Many who speak of receiving a "cortisone shot" or taking "cortisone" are actually receiving hydrocortisone or one of many other, much more potent synthetic corticosteroids; it is unlikely that the drug administered is actually cortisone. 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

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

ly,

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid ** Oral administration of medicines ** Oral examination (also known as an oral exam or or ...

ly,

intra-articular A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw- ...

ly (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. 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. It must be converted to cortisol by the action of

. 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. A cortisone injection may provide short-term pain relief and may reduce the swelling from

inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

of a

joint A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw- ...

tendon A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle to bone. It is able to transmit the mechanical forces of muscle contraction to the skeletal system without sacrificing its ability ...

, or

bursa ( grc-gre, Προῦσα, Proûsa, Latin: Prusa, ota, بورسه, Arabic:بورصة) is a city in northwestern Turkey and the administrative center of Bursa Province. The fourth-most populous city in Turkey and second-most populous in the ...

in, for example, the joints of the

knee In humans and other primates, the knee joins the thigh with the leg and consists of two joints: one between the femur and tibia (tibiofemoral joint), and one between the femur and patella (patellofemoral joint). It is the largest joint in the ...

, elbow and

shoulder The human shoulder is made up of three bones: the clavicle (collarbone), the scapula (shoulder blade), and the humerus (upper arm bone) as well as associated muscles, ligaments and tendons. The articulations between the bones of the shoulder mak ...

and into a broken

coccyx The coccyx ( : coccyges or coccyxes), commonly referred to as the tailbone, is the final segment of the vertebral column in all apes, and analogous structures in certain other mammals such as horses. In tailless primates (e.g. humans and othe ...

. Cortisone is also used by dermatologists to treat

keloid Keloid, also known as keloid disorder and keloidal scar, is the formation of a type of scar which, depending on its maturity, is composed mainly of either type III (early) or type I (late) collagen. It is a result of an overgrowth of granulation ...

s, relieve the symptoms of

eczema Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved c ...

and

atopic dermatitis Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin ( dermatitis). It results in itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which often thickens over tim ...

, and stop the development of

sarcoidosis Sarcoidosis (also known as ''Besnier-Boeck-Schaumann disease'') is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly af ...

Side effects

Oral use of cortisone has a number of potential systemic adverse effects, including

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...

hyperglycemia Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...

insulin resistance Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood sugar ...

diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone a ...

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

, depression, amenorrhoea,

cataracts A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble ...

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for aqueous humor, fluid withi ...

, Cushing's syndrome, increased risk of infections and impaired growth. With topical application, it can lead to thinning of the skin, impaired wound healing, increased skin pigmentation, tendon rupture and skin infections (including abscesses).

History

Cortisone was first identified by the American chemists Edward Calvin Kendall and Harold L. Mason while researching at the

Mayo Clinic The Mayo Clinic () is a nonprofit American academic medical center focused on integrated health care, education, and research. It employs over 4,500 physicians and scientists, along with another 58,400 administrative and allied health staf ...

."I Went to See the Elephant" autobiography of Dwight J. Ingle, published by Vantage Press (1963), pg 94, 109 During the discovery process, cortisone was known as compound E (while

was known as compound F). In 1949,

Philip S. Hench Philip Showalter Hench (February 28, 1896 – March 30, 1965) was an American physician. Hench, along with his Mayo Clinic co-worker Edward Calvin Kendall and Swiss chemist Tadeus Reichstein was awarded the Nobel Prize for Physiology or Medicine ...

and colleagues discovered that large doses of injected cortisone were effective in the treatment of patients with severe

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are inv ...

. Kendall was awarded the 1950 Nobel Prize for Physiology or Medicine along with

Philip Showalter Hench Philip Showalter Hench (February 28, 1896 – March 30, 1965) was an American physician. Hench, along with his Mayo Clinic co-worker Edward Calvin Kendall and Swiss chemist Tadeus Reichstein was awarded the Nobel Prize for Physiology or Medicine ...

and Tadeusz Reichstein for the discovery of the structure and function of

adrenal cortex The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. It is ...

hormones including cortisone. 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. Mason's contributions to the crystallization and characterization of the compound have generally been forgotten outside of the Mayo Clinic. Cortisone was first produced commercially by Merck & Co. in 1948 or 1949. On September 30, 1949, Percy Julian announced an improvement in the process of producing cortisone from

bile acid Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primar ...

s. This eliminated the need to use osmium tetroxide, a rare, expensive, and dangerous chemical. In the UK in the early 1950s,

John Cornforth Sir John Warcup Cornforth Jr., (7 September 1917 – 8 December 2013) was an AustralianBritish chemist who won the Nobel Prize in Chemistry in 1975 for his work on the stereochemistry of enzyme-catalysed reactions, becoming the only Nobel ...

and

Kenneth Callow Robert Kenneth Callow, FRS (15 February 1901 – 1983) was a British biochemist. He worked at the National Institute for Medical Research (NIMR, Medical Research Council) in Hampstead and Mill Hill, where his work on steroids included contribu ...

at the National Institute for Medical Research collaborated with Glaxo to produce cortisone from hecogenin from sisal plants.

Production

Cortisone is one of several end-products of a process called steroidogenesis. This process starts with the synthesis of

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell memb ...

, which then proceeds through a series of modifications in the

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex ...

to become any one of many steroid hormones. One end-product of this pathway is

. For cortisol to be released from the adrenal gland, a cascade of signaling occurs. Corticotropin-releasing hormone released from the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus ...

stimulates corticotrophs in the

anterior pituitary A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the pi ...

to release ACTH, which relays the signal to the adrenal cortex. Here, the

zona fasciculata The ''zona fasciculata'' (sometimes, fascicular or fasciculate zone) constitutes the middle and also the widest zone of the adrenal cortex, sitting directly beneath the ''zona glomerulosa''. Constituent cells are organized into bundles or "fascicl ...

and

zona reticularis The zona reticularis (sometimes, reticulate zone) is the innermost layer of the adrenal cortex, lying deep to the zona fasciculata and superficial to the adrenal medulla. The cells are arranged cords that project in different directions giving a n ...

, in response to ACTH, secrete glucocorticoids, in particular cortisol. In various peripheral tissues, notably the kidneys, cortisol is inactivated to cortisone by the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

corticosteroid 11-beta-dehydrogenase isozyme 2. This is crucial because cortisol is a potent

mineralocorticoid Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances ( electrolyte balance and fluid balance). The primary ...

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. Because cortisone must be converted to cortisol before being active as a glucocorticoid, its activity is less than simply administering cortisol directly (80–90%).

Popular culture

Addiction to cortisone was the subject of the 1956 motion picture ''

Bigger Than Life ''Bigger Than Life'' is a 1956 American drama film directed by Nicholas Ray and starring James Mason, Barbara Rush, and Walter Matthau. Its plot follows an ailing school teacher and family man whose life spins out of control when he misuses cor ...

'', produced by and starring

James Mason James Neville Mason (; 15 May 190927 July 1984) was an English actor. He achieved considerable success in British cinema before becoming a star in Hollywood. He was the top box-office attraction in the UK in 1944 and 1945; his British films inc ...

. Though it was a box-office flop upon its initial release, many modern critics hail the film as a masterpiece and brilliant indictment of contemporary attitudes toward mental illness and addiction. In 1963,

Jean-Luc Godard Jean-Luc Godard ( , ; ; 3 December 193013 September 2022) was a French-Swiss film director, screenwriter, and film critic. He rose to prominence as a pioneer of the French New Wave film movement of the 1960s, alongside such filmmakers as Fran ...

named it one of the ten greatest American sound films ever made. John F. Kennedy was regularly administered

s such as cortisone as a treatment for

Addison's disease Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrena ...

Notes

Bibliography

* * * * * {{Authority control Corticosteroids Pregnanes Prodrugs Triketones