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Cortisone

February 15, 2024

Not to be confused with cortisol.

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.

Cortisone
Names
Pronunciation /ˈkɔːrtɪsoʊn/, /ˈkɔːrtɪzoʊn/
IUPAC name
17α,21-Dihydroxypregn-4-ene-3,11,20-trione
Systematic IUPAC name
(1R,3aS,3bS,9aR,9bS,11aS)-1-Hydroxy-1-(hydroxyacetyl)-9a,11a-dimethyl-2,3,3a,3b,4,5,8,9,9a,9b,11,11a-dodecahydro-7H-cyclopenta[a]phenanthrene-7,10(1H)-dione
Other names
17α,21-Dihydroxy-11-ketoprogesterone; 17α-Hydroxy-11-dehydrocorticosterone
Identifiers
  • 53-06-5 Y
3D model (JSmol)
  • Interactive image
ChEBI
  • CHEBI:16962 Y
ChEMBL
  • ChEMBL111861 N
ChemSpider
  • 193441 Y
ECHA InfoCard 100.000.149
  • 5171
KEGG
  • D07749 Y
MeSH Cortisone
  • 222786
UNII
  • V27W9254FZ Y
  • DTXSID5022857
  • InChI=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 Y
    Key: MFYSYFVPBJMHGN-ZPOLXVRWSA-N Y
  • 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
    Key: MFYSYFVPBJMHGN-ZPOLXVRWBW
  • 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
Properties
C21H28O5
Molar mass 360.450 g·mol−1
Melting point 220 to 224 °C (428 to 435 °F; 493 to 497 K)
Pharmacology
H02AB10 (WHO) S01BA03 (WHO)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)

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 edit

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.

A cortisone injection may provide short-term pain relief and may reduce the swelling from inflammation of a joint, tendon, or bursa in, for example, the joints of the knee, elbow and shoulder[1] and into a broken coccyx.[5]

Cortisone is used by dermatologists to treat keloids,[6] relieve the symptoms of eczema and atopic dermatitis,[7] and stop the development of sarcoidosis.[8]

Side effects edit

Oral use of cortisone has a number of potential systemic adverse effects, including asthma, hyperglycemia, insulin resistance, diabetes mellitus, osteoporosis, anxiety, depression, amenorrhoea, cataracts, glaucoma, Cushing's syndrome, increased risk of infections, and impaired growth.[1][2] With topical application, it can lead to thinning of the skin, impaired wound healing, increased skin pigmentation, tendon rupture, and skin infections (including abscesses).[9]

History edit

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 was first produced commercially by Merck & Co. in 1948 or 1949.[13][16] On September 30, 1949, Percy Julian announced an improvement in the process of producing cortisone from bile acids.[17] 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.[18]

Production edit

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.[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 edit

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]

John F. Kennedy was regularly administered corticosteroids such as cortisone as a treatment for Addison's disease.[23]

See also edit

Notes edit

  1. ^ a b c "Cortisone shots". MayoClinic.com. 2010-11-16. Retrieved July 31, 2013.
  2. ^ a b "Prednisone and other corticosteroids: Balance the risks and benefits". MayoClinic.com. 2010-06-05. Retrieved 2017-12-21.
  3. ^ Martindale, William; Reynolds, James, eds. (1993). Martindale, The Extra Pharmacopoeia (30th ed.). Pharmaceutical Press. p. 726. ISBN 978-0853693000.
  4. ^ a b Cooper MS, Stewart PM (2009). "11Beta-hydroxysteroid dehydrogenase type 1 and its role in the hypothalamus-pituitary-adrenal axis, metabolic syndrome, and inflammation". J Clin Endocrinol Metab. 94 (12): 4645–4654. doi:10.1210/jc.2009-1412. PMID 19837912.
  5. ^ "injections and needles for coccyx pain". www.coccyx.org.
  6. ^ Zanon, E; Jungwirth, W; Anderl, H (1992). "Cortisone jet injection as therapy of hypertrophic keloids". Handchirurgie, Mikrochirurgie, Plastische Chirurgie. 24 (2): 100–2. PMID 1582609.
  7. ^ . National Eczema Association. Archived from the original on 2012-01-30. Retrieved 2013-05-07.
  8. ^ Bogart, A.S.; Daniel, D.D.; Poster, K.G. (1954). "Cortisone Treatment of Sarcoidosis". Diseases of the Chest. 26 (2): 224–228. doi:10.1378/chest.26.2.224. PMID 13182965.
  9. ^ Cole, BJ; Schumacher (Jan–Feb 2005). "Injectable Corticosteroids in Modern Practice". Journal of the American Academy of Orthopaedic Surgeons. 13 (1): 37–46. CiteSeerX 10.1.1.562.1931. doi:10.5435/00124635-200501000-00006. PMID 15712981. S2CID 18658724.
  10. ^ "Cortisone Discovery and the Nobel Prize". Mayo Clinic. Retrieved 2009-07-04.
  11. ^ a b c "I Went to See the Elephant" autobiography of Dwight J. Ingle, published by Vantage Press (1963), pg 94, 109
  12. ^ Mason, Harold L.; Myers, Charles S.; Kendall, Edward C. (1936). "The chemistry of crystalline substances isolated from the suprarenal gland" (PDF). J. Biol. Chem. 114 (3): 613. doi:10.1016/S0021-9258(18)74790-X. Retrieved 2014-09-07.
  13. ^ a b Thomas L. Lemke; David A. Williams (2008). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 889–. ISBN 978-0-7817-6879-5.
  14. ^ "The Nobel Prize in Physiology or Medicine 1950". The Nobel Prize. The Nobel Foundation. 2021. Retrieved 2 April 2021.
  15. ^ Glyn, J (1998). "The discovery and early use of cortisone". J R Soc Med. 91 (10): 513–517. doi:10.1177/014107689809101004. PMC 1296908. PMID 10070369.
  16. ^ Calvert DN (1962). "Anti-inflammatory steroids". Wis. Med. J. 61: 403–4. PMID 13875857.
  17. ^ Gibbons, Ray (1949). "Science gets synthetic key to rare drug; discovery is made in Chicago". Chicago Tribune. Chicago. p. 1.
  18. ^ 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. PMID 16337555.
  19. ^ "Corticosteroid Dose Equivalents". Medscape. Retrieved 20 December 2016.
  20. ^ Cossar 2011, p. 273.
  21. ^ Halliwell 2013, pp. 159–162.
  22. ^ Marshall, Colin (December 2, 2013). "A Young Jean-Luc Godard Picks the 10 Best American Films Ever Made (1963)". Open Culture.
  23. ^ Altman, Lawrence (October 6, 1992). "The doctor's world; Disturbing Issue of Kennedy's Secret Illness". The New York Times.

Bibliography edit

  • Bonagura J., DVM; et al. (2000). Current Veterinary Therapy. Vol. 13. pp. 321–381.
  • Cossar, Harper (2011). Letterboxed: The Evolution of Widescreen Cinema. University Press of Kentucky. ISBN 978-0-813-12651-7.
  • Halliwell, Martin (2013). Therapeutic Revolutions: Medicine, Psychiatry, and American Culture, 1945-1970. Rutgers University Press. ISBN 978-0-813-56066-3.
  • Ingle DJ (October 1950). "The biologic properties of cortisone: a review". J. Clin. Endocrinol. Metab. 10 (10): 1312–54. doi:10.1210/jcem-10-10-1312. PMID 14794756.[permanent dead link]
  • Woodward R. B.; Sondheimer F.; Taub D. (1951). "The Total Synthesis of Cortisone". Journal of the American Chemical Society. 73 (8): 4057. doi:10.1021/ja01152a551.

February 15, 2024
cortisone, confused, with, cortisol, pregnene, carbon, steroid, hormone, naturally, occurring, corticosteroid, metabolite, that, also, used, pharmaceutical, prodrug, cortisol, converted, action, enzyme, corticosteroid, beta, dehydrogenase, isozyme, into, inact. Not to be confused with cortisol 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 11b Hydroxysteroid dehydrogenase type 1 particularly in the liver Cortisone NamesPronunciation ˈ k ɔːr t ɪ s oʊ n ˈ k ɔːr t ɪ z oʊ n IUPAC name 17a 21 Dihydroxypregn 4 ene 3 11 20 trioneSystematic IUPAC name 1R 3aS 3bS 9aR 9bS 11aS 1 Hydroxy 1 hydroxyacetyl 9a 11a dimethyl 2 3 3a 3b 4 5 8 9 9a 9b 11 11a dodecahydro 7H cyclopenta a phenanthrene 7 10 1H dioneOther names 17a 21 Dihydroxy 11 ketoprogesterone 17a Hydroxy 11 dehydrocorticosteroneIdentifiersCAS Number 53 06 5 Y3D model JSmol Interactive imageChEBI CHEBI 16962 YChEMBL ChEMBL111861 NChemSpider 193441 YECHA InfoCard 100 000 149IUPHAR BPS 5171KEGG D07749 YMeSH CortisonePubChem CID 222786UNII V27W9254FZ YCompTox Dashboard EPA DTXSID5022857InChI InChI 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 YKey MFYSYFVPBJMHGN ZPOLXVRWSA N YInChI 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 s1Key MFYSYFVPBJMHGN ZPOLXVRWBWSMILES 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 23CPropertiesChemical formula C 21H 28O 5Molar mass 360 450 g mol 1Melting point 220 to 224 C 428 to 435 F 493 to 497 K PharmacologyATC code H02AB10 WHO S01BA03 WHO Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references 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 Contents 1 Effects and uses 2 Side effects 3 History 4 Production 5 Popular culture 6 See also 7 Notes 8 BibliographyEffects and uses editCortisone itself is inactive 3 It must be converted to cortisol by the action of 11b 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 11b 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 in for example the joints of the knee elbow and shoulder 1 and into a broken coccyx 5 Cortisone is used by dermatologists to treat keloids 6 relieve the symptoms of eczema and atopic dermatitis 7 and stop the development of sarcoidosis 8 Side effects editOral use of cortisone has a number of potential systemic adverse effects including asthma hyperglycemia insulin resistance diabetes mellitus osteoporosis anxiety depression amenorrhoea cataracts glaucoma Cushing s syndrome increased risk of infections and impaired growth 1 2 With topical application it can lead to thinning of the skin impaired wound healing increased skin pigmentation tendon rupture and skin infections including abscesses 9 History editCortisone 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 was first produced commercially by Merck amp Co in 1948 or 1949 13 16 On September 30 1949 Percy Julian announced an improvement in the process of producing cortisone from bile acids 17 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 18 Production editCortisone 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 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 editAddiction 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 John F Kennedy was regularly administered corticosteroids such as cortisone as a treatment for Addison s disease 23 See also edit nbsp Biology portal nbsp Medicine portal Central serous retinopathy CorticosterolNotes edit a b c Cortisone shots MayoClinic com 2010 11 16 Retrieved July 31 2013 a b Prednisone and other corticosteroids Balance the risks and benefits MayoClinic com 2010 06 05 Retrieved 2017 12 21 Martindale William Reynolds James eds 1993 Martindale The Extra Pharmacopoeia 30th ed Pharmaceutical Press p 726 ISBN 978 0853693000 a b Cooper MS Stewart PM 2009 11Beta hydroxysteroid dehydrogenase type 1 and its role in the hypothalamus pituitary adrenal axis metabolic syndrome and inflammation J Clin Endocrinol Metab 94 12 4645 4654 doi 10 1210 jc 2009 1412 PMID 19837912 injections and needles for coccyx pain www coccyx org Zanon E Jungwirth W Anderl H 1992 Cortisone jet injection as therapy of hypertrophic keloids Handchirurgie Mikrochirurgie Plastische Chirurgie 24 2 100 2 PMID 1582609 All About Atopic Dermatitis National Eczema Association Archived from the original on 2012 01 30 Retrieved 2013 05 07 Bogart A S Daniel D D Poster K G 1954 Cortisone Treatment of Sarcoidosis Diseases of the Chest 26 2 224 228 doi 10 1378 chest 26 2 224 PMID 13182965 Cole BJ Schumacher Jan Feb 2005 Injectable Corticosteroids in Modern Practice Journal of the American Academy of Orthopaedic Surgeons 13 1 37 46 CiteSeerX 10 1 1 562 1931 doi 10 5435 00124635 200501000 00006 PMID 15712981 S2CID 18658724 Cortisone Discovery and the Nobel Prize Mayo Clinic Retrieved 2009 07 04 a b c I Went to See the Elephant autobiography of Dwight J Ingle published by Vantage Press 1963 pg 94 109 Mason Harold L Myers Charles S Kendall Edward C 1936 The chemistry of crystalline substances isolated from the suprarenal gland PDF J Biol Chem 114 3 613 doi 10 1016 S0021 9258 18 74790 X Retrieved 2014 09 07 a b Thomas L Lemke David A Williams 2008 Foye s Principles of Medicinal Chemistry Lippincott Williams amp Wilkins pp 889 ISBN 978 0 7817 6879 5 The Nobel Prize in Physiology or Medicine 1950 The Nobel Prize The Nobel Foundation 2021 Retrieved 2 April 2021 Glyn J 1998 The discovery and early use of cortisone J R Soc Med 91 10 513 517 doi 10 1177 014107689809101004 PMC 1296908 PMID 10070369 Calvert DN 1962 Anti inflammatory steroids Wis Med J 61 403 4 PMID 13875857 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 PMID 16337555 Corticosteroid Dose Equivalents Medscape Retrieved 20 December 2016 Cossar 2011 p 273 Halliwell 2013 pp 159 162 Marshall Colin December 2 2013 A Young Jean Luc Godard Picks the 10 Best American Films Ever Made 1963 Open Culture Altman Lawrence October 6 1992 The doctor s world Disturbing Issue of Kennedy s Secret Illness The New York Times Bibliography editBonagura J DVM et al 2000 Current Veterinary Therapy Vol 13 pp 321 381 Cossar Harper 2011 Letterboxed The Evolution of Widescreen Cinema University Press of Kentucky ISBN 978 0 813 12651 7 Halliwell Martin 2013 Therapeutic Revolutions Medicine Psychiatry and American Culture 1945 1970 Rutgers University Press ISBN 978 0 813 56066 3 Ingle DJ October 1950 The biologic properties of cortisone a review J Clin Endocrinol Metab 10 10 1312 54 doi 10 1210 jcem 10 10 1312 PMID 14794756 permanent dead link Woodward R B Sondheimer F Taub D 1951 The Total Synthesis of Cortisone Journal of the American Chemical Society 73 8 4057 doi 10 1021 ja01152a551 Retrieved from https en wikipedia org w index php title Cortisone amp oldid 1191599668, wikipedia, wiki, book, books, library,

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