Chemistry:21-Deoxycortisol

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21-Deoxycortisol
21-Deoxycortisol.svg
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
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).
Infobox references
Tracking categories (test):

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

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] Hence, the use of LC-MS/MS instead of immunoassays in cortisol measurement aims to provide greater specificity.[19]

Besides 21-deoxycortisol, another C21 steroid, 21-deoxycorticosterone (11β-hydroxyprogesterone), has been proposed as a marker for 21-hydroxylase deficiency,[20][21][22] 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.[23]

See also

References

  1. ↑ 1.0 1.1 1.2 "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. 2004. doi:10.1002/rcm.1284. PMID 14689562. Bibcode: 2004RCMS...18...77C. 
  2. ↑ "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. October 2023. doi:10.3390/ijns9040058. PMID 37873849. 
  3. ↑ "Congenital Adrenal Hyperplasia: Time to Replace 17OHP with 21-Deoxycortisol". Hormone Research in Paediatrics 91 (6): 416–420. 2019. doi:10.1159/000501396. PMID 31450227. 
  4. ↑ "Serum 21-deoxycortisol for diagnosis of non-classic congenital adrenal hyperplasia in women with androgen excess". J Clin Endocrinol Metab 108 (12): e1560–e1570. June 2023. doi:10.1210/clinem/dgad377. PMID 37358001. 
  5. ↑ "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. 2020. doi:10.1007/s40618-020-01235-3. PMID 32236851. 
  6. ↑ "21-Deoxycortisol is a Key Screening Marker for 21-Hydroxylase Deficiency". J Pediatr 242: 213–219.e1. March 2022. doi:10.1016/j.jpeds.2021.10.063. PMID 34780778. 
  7. ↑ 7.0 7.1 "Profiles of 21-Carbon Steroids in 21-hydroxylase Deficiency". The Journal of Clinical Endocrinology and Metabolism 100 (6): 2283–2290. 2015. doi:10.1210/jc.2015-1023. PMID 25850025. 
  8. ↑ "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. November 2018. doi:10.1210/jc.2018-01865. 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. PMID 13271547. 
  10. ↑ "Measuring cortisol in serum, urine and saliva - are our assays good enough?". Annals of Clinical Biochemistry 54 (3): 308–322. May 2017. doi:10.1177/0004563216687335. PMID 28068807. 
  11. ↑ "Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency". The New England Journal of Medicine 383 (13): 1248–1261. September 2020. doi:10.1056/NEJMra1909786. PMID 32966723. 
  12. ↑ Endocrine Pharmacology: Physiological Basis and Therapeutic Applications. CUP Archive. 1980. pp. 158–. ISBN 978-0-521-22673-8. https://books.google.com/books?id=W6M9AAAAIAAJ&pg=PA158. 
  13. ↑ "Glucocorticoid Activity of Adrenal Steroid Precursors in Untreated Patients With Congenital Adrenal Hyperplasia". The Journal of Clinical Endocrinology and Metabolism 104 (11): 5065–5072. November 2019. doi:10.1210/jc.2019-00547. PMID 31090904. 
  14. ↑ "Cortisol - Clinical Indications and Laboratory Testing". AACC Clinical Laboratory News. 2012. https://www.aacc.org/Publications/CLN/Articles/2012/september/Cortisol.aspx. 
  15. ↑ "Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction". BMC Clinical Pathology 14 (33): 33. 2014. doi:10.1186/1472-6890-14-33. PMID 25071417. 
  16. ↑ "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. 2020. doi:10.1136/bcr-2020-235450. PMID 32900728. 
  17. ↑ "Non-Classical Congenital Adrenal Hyperplasia in Childhood". Journal of Clinical Research in Pediatric Endocrinology 9 (1): 1–7. 7 March 2017. doi:10.4274/jcrpe.3378. PMID 27354284. 
  18. ↑ "Endogenous glucocorticoid analysis by liquid chromatography-tandem mass spectrometry in routine clinical laboratories". The Journal of Steroid Biochemistry and Molecular Biology 162: 27–40. September 2016. doi:10.1016/j.jsbmb.2016.05.014. PMID 27208627. 
  19. ↑ "Clinical endocrinology and hormones quantitation: the increasing role of mass spectrometry". Minerva Endocrinologica 43 (3): 261–284. September 2018. doi:10.23736/S0391-1977.17.02764-X. PMID 29083134. 
  20. ↑ "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. 1987. doi:10.1016/0022-4731(87)90043-4. PMID 3546944. 
  21. ↑ "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. 1989. doi:10.1210/jcem-68-3-542. PMID 2537337. 
  22. ↑ "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. 2017. doi:10.1210/js.2016-1048. PMID 29264476. 
  23. ↑ "Utility of a Commercially Available Blood Steroid Profile in Endocrine Practice". Indian Journal of Endocrinology and Metabolism 23 (1): 97–101. 2019. doi:10.4103/ijem.IJEM_531_18. PMID 31016162. 

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