View source for Cortisone

{{Short description|Corticosteroid precursor and metabolite of cortisol}}
{{distinguish|cortisol}}
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 456660597
| pronounce = {{IPAc-en|ˈ|k|ɔːr|t|ᵻ|s|oʊ|n}}, {{IPAc-en|ˈ|k|ɔːr|t|ᵻ|z|oʊ|n}}
| ImageFile1 = {{wikidata|property|raw|P117}}
| ImageFile2 = {{wikidata|property|raw|P8224}}
| IUPACName = 17α,21-Dihydroxypregn-4-ene-3,11,20-trione
| SystematicName = (1''R'',3a''S'',3b''S'',9a''R'',9b''S'',11a''S'')-1-Hydroxy-1-(hydroxyacetyl)-9a,11a-dimethyl-2,3,3a,3b,4,5,8,9,9a,9b,11,11a-dodecahydro-7''H''-cyclopenta[''a'']phenanthrene-7,10(1''H'')-dione
| OtherNames = 17α,21-Dihydroxy-11-ketoprogesterone; 17α-Hydroxy-11-dehydrocorticosterone
|Section1={{Chembox Identifiers
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = V27W9254FZ
| IUPHAR_ligand = 5171
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 111861
| InChI = 1/C21H28O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h9,14-15,18,22,26H,3-8,10-11H2,1-2H3/t14-,15-,18+,19-,20-,21-/m0/s1
| InChIKey = MFYSYFVPBJMHGN-ZPOLXVRWBW
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C21H28O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h9,14-15,18,22,26H,3-8,10-11H2,1-2H3/t14-,15-,18+,19-,20-,21-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = MFYSYFVPBJMHGN-ZPOLXVRWSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 193441
| CASNo = 53-06-5
| PubChem = 222786
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07749
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 16962
| SMILES = O=C(CO)[C@@]3(O)CC[C@H]2[C@@H]4CC\C1=C\C(=O)CC[C@]1(C)[C@H]4C(=O)C[C@@]23C
| MeSHName = Cortisone
  }}
|Section2={{Chembox Properties
| C=21 | H=28 | O=5
| Appearance = 
| Density = 
| MeltingPtC = 220 to 224
| BoilingPt = 
  }}
|Section6={{Chembox Pharmacology
| ATCCode_prefix = H02
| ATCCode_suffix = AB10
| ATC_Supplemental = {{ATC|S01|BA03}}
}}
|Section7={{Chembox Hazards
| MainHazards = 
| FlashPt = 
| AutoignitionPt = 
  }}
}}
'''Cortisone''' is a [[pregnene]] (21-carbon) [[steroid hormone]]. It is a naturally-occurring [[corticosteroid]] metabolite that is also used as a pharmaceutical [[prodrug]]. [[Cortisol]] is converted by the action of the enzyme [[corticosteroid 11-beta-dehydrogenase isozyme 2]] into the inactive metabolite cortisone, particularly in the kidneys. This is done by [[oxidizing]] the alcohol group at carbon 11 (in the six-membered ring fused to the five-membered ring). Cortisone is converted back to the active steroid cortisol by [[stereospecific]] [[hydrogenation]] at carbon 11 by the enzyme [[11β-Hydroxysteroid dehydrogenase type 1]], particularly in the liver.

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 [[intravenous]]ly, [[oral administration|oral]]ly, [[intra-articular]]ly (into a joint), or [[Transdermal|transcutaneous]]ly. 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.<ref name=mayo>{{cite web|url=http://www.mayoclinic.com/health/cortisone-shots/MY00268 |title=Cortisone shots |publisher=MayoClinic.com |date=2010-11-16 |access-date=July 31, 2013}}</ref><ref name=mayorisk2>{{cite web|url=https://www.mayoclinic.org/steroids/art-20045692 |title=Prednisone and other corticosteroids: Balance the risks and benefits |publisher=MayoClinic.com |date=2010-06-05 |access-date=2017-12-21}}</ref> 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.<ref>{{cite book |editor1-last= Martindale |editor1-first= William |editor2-last= Reynolds |editor2-first= James |date=1993 |title= Martindale, The Extra Pharmacopoeia |edition=30th|publisher= Pharmaceutical Press |page=726 |isbn= 978-0853693000}}</ref> It must be converted to cortisol by the action of [[11β-hydroxysteroid dehydrogenase type 1]].<ref name="Cooper">{{cite journal |vauthors= Cooper MS, Stewart PM |date=2009 |title= 11Beta-hydroxysteroid dehydrogenase type 1 and its role in the hypothalamus-pituitary-adrenal axis, metabolic syndrome, and inflammation |journal= J Clin Endocrinol Metab |volume=94 |issue=12 |pages= 4645–4654 |doi=10.1210/jc.2009-1412 |pmid= 19837912|doi-access= free }}</ref> 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]] of a [[joint]], [[tendon]], or [[bursa (anatomy)|bursa]] in, for example, the joints of the [[knee]], [[elbow]] and [[shoulder]]<ref name=mayo/> and into a broken [[coccyx]].<ref>{{cite web|url=http://www.coccyx.org/treatmen/inflamm.htm|title=injections and needles for coccyx pain|website=www.coccyx.org}}</ref>

Cortisone is used by [[dermatologist]]s to treat [[keloid]]s,<ref>{{cite journal | pmid = 1582609 | year = 1992 | last1 = Zanon | first1 = E | last2 = Jungwirth | first2 = W | last3 = Anderl | first3 = H | title = Cortisone jet injection as therapy of hypertrophic keloids | volume = 24 | issue = 2 | pages = 100–2 | journal = Handchirurgie, Mikrochirurgie, Plastische Chirurgie}}</ref> relieve the symptoms of [[eczema]] and [[atopic dermatitis]],<ref>{{cite web | url = http://www.nationaleczema.org/living-with-eczema/all-about-atopic-dermatitis | title = All About Atopic Dermatitis | publisher = National Eczema Association}}</ref> and stop the development of [[sarcoidosis]].<ref>{{Cite journal |url=https://www.sciencedirect.com/science/article/pii/S0096021715323463 |title=Cortisone Treatment of Sarcoidosis |year=1954 |doi=10.1378/chest.26.2.224 |last1=Bogart |first1=A.S. |last2=Daniel |first2=D.D. |last3=Poster |first3=K.G. |journal=Diseases of the Chest |volume=26 |issue=2 |pages=224–228 |pmid=13182965 }}</ref>

==Side effects==
Oral use of cortisone has a number of potential systemic adverse effects, including [[asthma]], [[hyperglycemia]], [[insulin resistance]], [[diabetes mellitus]], [[osteoporosis]], [[anxiety]], [[Depression (mood)|depression]], [[amenorrhoea]], [[cataracts]], [[glaucoma]], [[Cushing's syndrome]], [[immunosuppression|increased risk of infections]], and [[growth impairment| impaired growth]]{{dn|date=June 2023}}.<ref name=mayo/><ref name=mayorisk2/> With [[topical application]], it can lead to thinning of the skin, impaired [[wound healing]], [[hyperpigmentation|increased skin pigmentation]], [[tendon rupture]], and [[skin infection]]s (including [[abscesses]]).<ref>{{cite journal|last=Cole|first=BJ|author2=Schumacher |title=Injectable Corticosteroids in Modern Practice|journal= Journal of the American Academy of Orthopaedic Surgeons|date=Jan–Feb 2005|volume=13|issue=1|pages=37–46|doi=10.5435/00124635-200501000-00006|pmid=15712981|citeseerx=10.1.1.562.1931|s2cid=18658724}}</ref>

==History==
Cortisone was first identified by the American chemists [[Edward Calvin Kendall]] and Harold L. Mason while researching at the [[Mayo Clinic]].<ref name="urlCortisone Discovery and the Nobel Prize">{{cite web |url=http://www.mayoclinic.org/tradition-heritage/cortisone-discovery.html |title=Cortisone Discovery and the Nobel Prize |website=[[Mayo Clinic]] |access-date=2009-07-04}}</ref><ref name="Ingle">"I Went to See the Elephant" autobiography of [[Dwight Ingle|Dwight J. Ingle]], published by Vantage Press (1963), pg 94, 109</ref><ref name="Mason/Myers/Kendall">{{cite journal|url=http://www.jbc.org/content/114/3/613.full.pdf|journal=J. Biol. Chem.|volume=114|page=613 |title=The chemistry of crystalline substances isolated from the suprarenal gland|year=1936|doi=10.1016/S0021-9258(18)74790-X|access-date=2014-09-07|last1=Mason|first1=Harold L.|last2=Myers|first2=Charles S.|last3=Kendall|first3=Edward C.|issue=3|doi-access=free}}</ref> 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]].<ref name="LemkeWilliams2008">{{cite book|author1=Thomas L. Lemke|author2=David A. Williams|title=Foye's Principles of Medicinal Chemistry|url=https://archive.org/details/foyesprinciplesm00lemk|url-access=limited|year=2008|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-6879-5|pages=[https://archive.org/details/foyesprinciplesm00lemk/page/n2289 889]–}}</ref> 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.<ref>{{cite web |url=https://www.nobelprize.org/prizes/medicine/1950/summary/ |title=The Nobel Prize in Physiology or Medicine 1950 |author=<!--Not stated--> |date=2021 |website=The Nobel Prize |publisher=The Nobel Foundation |access-date=2 April 2021 |quote=}}</ref><ref>{{cite journal |last1=Glyn |first1=J|date=1998 |title= The discovery and early use of cortisone|journal= J R Soc Med |volume=91 |issue=10 |pages=513–517 |doi=10.1177/014107689809101004 |pmc= 1296908 |pmid= 10070369 }}</ref> 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.<ref name="Ingle"/> Mason's contributions to the crystallization and characterization of the compound have generally been forgotten outside of the Mayo Clinic.<ref name="Ingle"/>

Cortisone was first produced commercially by [[Merck & Co.]] in 1948 or 1949.<ref name="LemkeWilliams2008" /><ref name="pmid13875857">{{cite journal | vauthors = Calvert DN | title = Anti-inflammatory steroids | journal = Wis. Med. J. | volume = 61 | pages = 403–4 | year = 1962 | pmid = 13875857 }}</ref> On September 30, 1949, [[Percy Lavon Julian|Percy Julian]] announced an improvement in the process of producing cortisone from [[bile acid]]s.<ref>{{cite news |last=Gibbons |first=Ray |date=1949 |title= Science gets synthetic key to rare drug; discovery is made in Chicago |work=Chicago Tribune |location=Chicago |page= 1}}</ref> This eliminated the need to use [[osmium tetroxide]], a rare, expensive, and dangerous chemical. In the UK in the early 1950s, [[John Cornforth]] and [[Kenneth Callow]] at the [[National Institute for Medical Research]] collaborated with [[Glaxo]] to produce cortisone from [[hecogenin]] from [[sisal]] plants.<ref>{{cite journal | doi = 10.1016/j.shpsc.2005.09.001 | pmid = 16337555 | title = Making British Cortisone: Glaxo and the development of Corticosteroids in Britain in the 1950s–1960s | year = 2005 | last1 = Quirke | first1 = Viviane | journal = Studies in History and Philosophy of Science Part C | volume = 36 | issue = 4 | pages = 645–674 }}</ref>

==Production==
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 [[enzyme]] [[corticosteroid 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.<ref name ="Cooper"/>

Because cortisone must be converted to cortisol before being active as a [[glucocorticoid]], its activity is less than simply administering cortisol directly (80–90%).<ref>{{Cite journal|title=Corticosteroid Dose Equivalents|url=http://emedicine.medscape.com/article/2172042-overview|journal=Medscape|access-date=20 December 2016}}</ref>

==Popular culture==
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,{{sfn|Cossar|2011|p=273}} many modern critics hail the film as a masterpiece and brilliant indictment of contemporary attitudes toward mental illness and addiction.{{sfn|Halliwell|2013|pp=159-162}} In 1963, [[Jean-Luc Godard]] named it one of the ten greatest American sound films ever made.<ref name=godard>{{cite web |url=http://www.openculture.com/2013/12/a-young-jean-luc-godard-picks-the-best-american-films-1963.html |title=A Young Jean-Luc Godard Picks the 10 Best American Films Ever Made (1963) |publisher=Open Culture |date=December 2, 2013 |last=Marshall |first=Colin}}</ref>

[[John F. Kennedy]] was regularly administered [[corticosteroid]]s such as cortisone as a treatment for [[Addison's disease]].<ref name=Kennedy>{{cite web |url=https://www.nytimes.com/1992/10/06/health/the-doctor-s-world-disturbing-issue-of-kennedy-s-secret-illness.html?pagewanted=all |title=The doctor's world; Disturbing Issue of Kennedy's Secret Illness |work=[[The New York Times]] |date=October 6, 1992 |last=Altman |first=Lawrence}}</ref>

==See also ==
* {{Portal-inline|Biology}}
* {{Portal-inline|Medicine}}
* [[Central serous retinopathy]]
* [[Corticosterol]]

==Notes==
{{reflist|30em}}

==Bibliography==
*{{cite book
| author= Bonagura J., DVM
| title= Current Veterinary Therapy
| year=2000
| pages=321–381
| volume=13 |display-authors=etal}}
* {{cite book |last=Cossar |first=Harper |title=Letterboxed: The Evolution of Widescreen Cinema |year=2011 |publisher=[[University Press of Kentucky]] |isbn=978-0-813-12651-7 |url=https://books.google.com/books?id=ql1mQBeuPBsC}}
* {{cite book |last=Halliwell |first=Martin |title=Therapeutic Revolutions: Medicine, Psychiatry, and American Culture, 1945-1970 |year=2013 |publisher=[[Rutgers University Press]] |isbn=978-0-813-56066-3 |url=https://books.google.com/books?id=lXMRAAAAQBAJ}}
* {{cite journal |author=Ingle DJ |title=The biologic properties of cortisone: a review |journal=J. Clin. Endocrinol. Metab. |volume=10 |issue=10 |pages=1312–54 |date=October 1950 |pmid=14794756 |doi=10.1210/jcem-10-10-1312 |url=http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=14794756 }}{{Dead link|date=July 2019 |bot=InternetArchiveBot |fix-attempted=yes }}
*{{cite journal
|author1=Woodward R. B. |author2=Sondheimer F. |author3=Taub D. | title= The Total Synthesis of Cortisone
| journal=Journal of the American Chemical Society
| year=1951
| pages=4057
| volume=73
| doi=10.1021/ja01152a551
| issue= 8 }}

{{Hormones}}
{{Endogenous steroids}}
{{Orexigenics}}
{{Glucocorticoids and antiglucocorticoids}}
{{Glucocorticoid receptor modulators}}
{{Authority control}}

[[Category:Corticosteroids]]
[[Category:Pregnanes]]
[[Category:Prodrugs]]
[[Category:Triketones]]