21-Deoxycortisol

21-Deoxycortisol
Names
IUPAC name
11β,17α-Dihydroxypregn-4-ene-3,20-dione
Systematic IUPAC name
(1R,3aS,3bS,9aR,9bS,10S,11aS)-1-Acetyl-1,10-dihydroxy-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9a,9b,10,11,11a-tetradecahydro-7H-cyclopenta[a]phenanthren-7-one
Other names
21-Desoxycortisol; 21-Dehydrohydrocortisone; 21-Deoxyhydrocortisone; 11β,17α-Dihydroxyprogesterone
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
KEGG
UNII
  • InChI=1S/C21H30O4/c1-12(22)21(25)9-7-16-15-5-4-13-10-14(23)6-8-19(13,2)18(15)17(24)11-20(16,21)3/h10,15-18,24-25H,4-9,11H2,1-3H3/t15-,16-,17-,18+,19-,20-,21-/m0/s1
    Key: LCZBQMKVFQNSJR-UJPCIWJBSA-N
  • CC(=O)[C@]1(CC[C@@H]2[C@@]1(C[C@@H]([C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)O)C)O
Properties
C21H30O4
Molar mass 346.467 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

21-Deoxycortisol, also known as 11β,17α-dihydroxyprogesterone or as 11β,17α-dihydroxypregn-4-ene-3,20-dione, is a naturally occurring, endogenous steroid related to cortisol (11β,17α,21-trihydroxyprogesterone) which is formed as a metabolite from 17α-hydroxyprogesterone via 11β-hydroxylase.[1]

Marker of 21-hydroxylase deficiency

[edit]

21-deoxycortisol is a marker of congenital adrenal hyperplasia due to 21-hydroxylase deficiency,[2][1][3] even in mild (non-classic) cases.[4][5] It can be also used for newborn screening.[6]

The deficiency of the 21-hydroxylase enzyme leads to excess of 17α-hydroxyprogesterone,[7][8] a 21-carbon (C21) steroid. This excess is accompanied by the accumulation of other C21 steroids, such as 21-deoxycortisol, which is formed by the 11β-hydroxylation of 17α-hydroxyprogesterone[7] via 11β-hydroxylase (CYP11B1).[1] The build-up of 21-deoxycortisol in patients with congenital adrenal hyperplasia have been described since at least 1955, this steroid was then called "21-desoxyhydrocortisone".[9][10] Unlike 17α-hydroxyprogesterone, 21-deoxycortisol is not produced in the gonads and is uniquely adrenal-derived. Hence, 21-deoxycortisol is a more specific biomarker of 21-hydroxylase deficiency than is 17α-hydroxyprogesterone.[11]

The corticosteroid activity of 21-deoxycortisol is lower than that of cortisol.[12][13]

As 21-deoxycortisol can be at high levels in congenital adrenal hyperplasia, and it has structural similarity to cortisol, it can cross-react in immunoassays,[14][15][16] resulting in a falsely normal or high cortisol result, when the true cortisol is actually low. Whereas immunoassays can suffer from cross-reactivity due to interactions with structural analogues, the selectivity offered by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has largely overcome these limitations.[17][18][19] Hence, the use of LC-MS/MS instead of immunoassays in cortisol measurement aims to provide greater specificity.[20]

Besides 21-deoxycortisol, another C21 steroid, 21-deoxycorticosterone (11β-hydroxyprogesterone), has been proposed as a marker for 21-hydroxylase deficiency,[21][22][23] but this marker did not gain acceptance due to the fact that testing for the levels of this steroid is not routinely offered by diagnostic laboratories.[24]

See also

[edit]

References

[edit]
  1. ^ a b c Cristoni S, Cuccato D, Sciannamblo M, Bernardi LR, Biunno I, Gerthoux P, Russo G, Weber G, Mora S (2004). "Analysis of 21-deoxycortisol, a marker of congenital adrenal hyperplasia, in blood by atmospheric pressure chemical ionization and electrospray ionization using multiple reaction monitoring". Rapid Commun. Mass Spectrom. 18 (1): 77–82. Bibcode:2004RCMS...18...77C. doi:10.1002/rcm.1284. PMID 14689562.
  2. ^ Greaves RF, Kumar M, Mawad N, Francescon A, Le C, O'Connell M, Chi J, Pitt J (October 2023). "Best Practice for Identification of Classical 21-Hydroxylase Deficiency Should Include 21 Deoxycortisol Analysis with Appropriate Isomeric Steroid Separation". Int J Neonatal Screen. 9 (4): 58. doi:10.3390/ijns9040058. PMC 10594498. PMID 37873849.
  3. ^ Miller WL (2019). "Congenital Adrenal Hyperplasia: Time to Replace 17OHP with 21-Deoxycortisol". Hormone Research in Paediatrics. 91 (6): 416–420. doi:10.1159/000501396. PMID 31450227. S2CID 201733086.
  4. ^ Ng JL, Lim EM, Zhang R, Beilby JP, Watts GF, Brown SJ, Stuckey BGA (June 2023). "Serum 21-deoxycortisol for diagnosis of non-classic congenital adrenal hyperplasia in women with androgen excess". J Clin Endocrinol Metab. 108 (12): e1560–e1570. doi:10.1210/clinem/dgad377. PMC 10655544. PMID 37358001. S2CID 259249719.
  5. ^ Oriolo C, Fanelli F, Castelli S, Mezzullo M, Altieri P, Corzani F, Pelusi C, Repaci A, Di Dalmazi G, Vicennati V, Baldazzi L, Menabò S, Dormi A, Nardi E, Brillanti G, Pasquali R, Pagotto U, Gambineri A (2020). "Steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency in a population of PCOS with suspicious levels of 17OH-progesterone". Journal of Endocrinological Investigation. 43 (10): 1499–1509. doi:10.1007/s40618-020-01235-3. PMID 32236851. S2CID 214715756.
  6. ^ Held PK, Bialk ER, Lasarev MR, Allen DB (March 2022). "21-Deoxycortisol is a Key Screening Marker for 21-Hydroxylase Deficiency". J Pediatr. 242: 213–219.e1. doi:10.1016/j.jpeds.2021.10.063. PMID 34780778. S2CID 244106268.
  7. ^ a b Turcu AF, Rege J, Chomic R, Liu J, Nishimoto HK, Else T, Moraitis AG, Palapattu GS, Rainey WE, Auchus RJ (2015). "Profiles of 21-Carbon Steroids in 21-hydroxylase Deficiency". The Journal of Clinical Endocrinology and Metabolism. 100 (6): 2283–2290. doi:10.1210/jc.2015-1023. PMC 4454804. PMID 25850025.
  8. ^ Speiser PW, Arlt W, Auchus RJ, Baskin LS, Conway GS, Merke DP, et al. (November 2018). "Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology and Metabolism. 103 (11): 4043–4088. doi:10.1210/jc.2018-01865. PMC 6456929. PMID 30272171.
  9. ^ JAILER JW, GOLD JJ, VANDE WIELE R, LIEBERMAN S (1955). "17alpha-hydroxyprogesterone and 21-desoxyhydrocortisone; their metabolism and possible role in congenital adrenal virilism". The Journal of Clinical Investigation. 34 (11): 1639–46. doi:10.1172/JCI103217. PMC 438744. PMID 13271547.
  10. ^ El-Farhan N, Rees DA, Evans C (May 2017). "Measuring cortisol in serum, urine and saliva - are our assays good enough?". Annals of Clinical Biochemistry. 54 (3): 308–322. doi:10.1177/0004563216687335. PMID 28068807. S2CID 206397561.
  11. ^ Merke DP, Auchus RJ (September 2020). "Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency". The New England Journal of Medicine. 383 (13): 1248–1261. doi:10.1056/NEJMra1909786. PMID 32966723. S2CID 221884108.
  12. ^ Endocrine Pharmacology: Physiological Basis and Therapeutic Applications. CUP Archive. 1980. pp. 158–. ISBN 978-0-521-22673-8.
  13. ^ Engels M, Pijnenburg-Kleizen KJ, Utari A, Faradz SM, Oude-Alink S, van Herwaarden AE, Span PN, Sweep FC, Claahsen-van der Grinten HL (November 2019). "Glucocorticoid Activity of Adrenal Steroid Precursors in Untreated Patients With Congenital Adrenal Hyperplasia". The Journal of Clinical Endocrinology and Metabolism. 104 (11): 5065–5072. doi:10.1210/jc.2019-00547. PMID 31090904.
  14. ^ Winter WE, Bazydlo L, Harris NS (2012). "Cortisol - Clinical Indications and Laboratory Testing". AACC Clinical Laboratory News. Archived from the original on 4 January 2018.
  15. ^ Krasowski MD, Drees D, Morris CS, Maakestad J, Blau JL, Ekins S (2014). "Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction". BMC Clinical Pathology. 14 (33): 33. doi:10.1186/1472-6890-14-33. PMC 4112981. PMID 25071417.
  16. ^ Agrawal N, Chakraborty PP, Sinha A, Maiti A (2020). "False elevation of serum cortisol in chemiluminescence immunoassay by Siemens Advia Centaur XP system in 21-hydroxylase deficiency: An 'endocrine laboma'". BMJ Case Reports. 13 (9): e235450. doi:10.1136/bcr-2020-235450. PMC 7477984. PMID 32900728. S2CID 221567576.
  17. ^ Tiulpakov MA, Nagaeva EV, Kalinchenko NY, Bezlepkina OB (January 2024). "[A promising approach for therapy control in congenital adrenal hyperplasia. Problems of Endocrinology]". Probl Endokrinol (Mosk) (in Russian). 69 (6): 102–108. doi:10.14341/probl13328. PMC 10848187. PMID 38311999.
  18. ^ Kurtoğlu S, Hatipoğlu N (7 March 2017). "Non-Classical Congenital Adrenal Hyperplasia in Childhood". Journal of Clinical Research in Pediatric Endocrinology. 9 (1): 1–7. doi:10.4274/jcrpe.3378. PMC 5363159. PMID 27354284.
  19. ^ Hawley JM, Keevil BG (September 2016). "Endogenous glucocorticoid analysis by liquid chromatography-tandem mass spectrometry in routine clinical laboratories". The Journal of Steroid Biochemistry and Molecular Biology. 162: 27–40. doi:10.1016/j.jsbmb.2016.05.014. PMID 27208627. S2CID 206501499.
  20. ^ D'aurizio F, Cantù M (September 2018). "Clinical endocrinology and hormones quantitation: the increasing role of mass spectrometry". Minerva Endocrinologica. 43 (3): 261–284. doi:10.23736/S0391-1977.17.02764-X. PMID 29083134. S2CID 12984040.
  21. ^ Gueux B, Fiet J, Galons H, Boneté R, Villette J, Vexiau P, Pham-Huu-Trung M, Raux-Eurin M, Gourmelen M, Brérault J, Julien R, Dreux C (1987). "The measurement of 11 beta-hydroxy-4-pregnene-3,20-dione (21-deoxycorticosterone) by radioimmunoassay in human plasma". Journal of Steroid Biochemistry. 26 (1): 145–50. doi:10.1016/0022-4731(87)90043-4. PMID 3546944.
  22. ^ Fiet J, Gueux B, Rauxdemay M, Kuttenn F, Vexiau P, Brerault J, Couillin P, Galons H, Villette J, Julien R, Dreux C (1989). "Increased plasma 21-deoxycorticosterone (21-DB) levels in late-onset adrenal 21-hydroxylase deficiency suggest a mild defect of the mineralocorticoid pathway". The Journal of Clinical Endocrinology and Metabolism. 68 (3): 542–7. doi:10.1210/jcem-68-3-542. PMID 2537337.
  23. ^ Fiet J, Le Bouc Y, Guéchot J, Hélin N, Maubert MA, Farabos D, Lamazière A (2017). "A Liquid Chromatography/Tandem Mass Spectometry [sic] Profile of 16 Serum Steroids, Including 21-Deoxycortisol and 21-Deoxycorticosterone, for Management of Congenital Adrenal Hyperplasia". Journal of the Endocrine Society. 1 (3): 186–201. doi:10.1210/js.2016-1048. PMC 5686660. PMID 29264476.
  24. ^ Sarathi V, Atluri S, Pradeep TV, Rallapalli SS, Rakesh CV, Sunanda T, Kumar KD (2019). "Utility of a Commercially Available Blood Steroid Profile in Endocrine Practice". Indian Journal of Endocrinology and Metabolism. 23 (1): 97–101. doi:10.4103/ijem.IJEM_531_18. PMC 6446682. PMID 31016162.
[edit]


Stub icon

This article about a steroid is a stub. You can help Wikipedia by expanding it.

Retrieved from "https://en.wikipedia.org/w/index.php?title=21-Deoxycortisol&oldid=1209184559"