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21-Deoxycortisol

(Synonyms: 脱氧皮质醇) 目录号 : GC46526

A corticosteroid metabolite of 17-hydroxyprogesterone

21-Deoxycortisol Chemical Structure

Cas No.:641-77-0

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产品描述

21-Deoxycortisol is a corticosteroid metabolite of 17-hydroxyprogesterone produced in the adrenal gland via 11-hydroxylation by 11β-hydroxylase.1,2 Serum levels of 21-deoxycortisol are elevated in patients with congenital adrenal hyperplasia that are heterozygous for mutations in CYP2A21, the gene encoding steroid 21-hydroxylase, and have been used as a biomarker for the detection of 21-hydroxylase deficiencies.

1.Fiet, J., Villette, J.-M., Galons, H., et al.The application of a new highly-sensitive radioimmunoassay for plasma 21-deoxycortisol to the detection of steroid-21-hydroxylase deficiencyAnn. Clin. Biochem.31(Pt. 1)56-64(1994) 2.Cristoni, S., Cuccato, D., Sciannamblo, M., et al.Analysis of 21-deoxycortisol, a marker of congenital adrenal hyperplasia, in blood by atmospheric pressure chemical ionization and electrospray ionization using multiple reaction monitoringRapid Commun. Mass Spectrom.18(1)77-82(2004)

Chemical Properties

Cas No. 641-77-0 SDF
别名 脱氧皮质醇
Canonical SMILES O=C(C)[C@@]1(O)CC[C@@]2([H])[C@]3([H])CCC4=CC(CC[C@]4(C)[C@@]3([H])[C@@H](O)C[C@@]21C)=O
分子式 C21H30O4 分子量 346.5
溶解度 DMSO : 100 mg/mL (288.63 mM; Need ultrasonic) 储存条件 Store at -20°C
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1 mg 5 mg 10 mg
1 mM 2.886 mL 14.43 mL 28.86 mL
5 mM 0.5772 mL 2.886 mL 5.772 mL
10 mM 0.2886 mL 1.443 mL 2.886 mL
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Research Update

Congenital Adrenal Hyperplasia: Time to Replace 17OHP with 21-Deoxycortisol

Horm Res Paediatr 2019;91(6):416-420.PMID:31450227DOI:10.1159/000501396.

Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency (21OHD) has a worldwide incidence of 1 in 15-20,000. Affected individuals have adrenal insufficiency and androgen excess; the androgen excess begins during fetal life, typically resulting in 46,XX disordered sexual development. In 21OHD, 17-hydroxyprogesterone (17OHP), the steroid proximal to 21-hydroxylase, accumulates. Most industrialized countries have newborn screening programs that measure 17OHP; such screening has permitted rapid detection of newborns with 21OHD, saving lives previously lost to mineralocorticoid deficiency and salt wasting. However, newborn screening is plagued by false positives. 17OHP is above most "cutoff values" in the first 24 h of life, is high in otherwise normal premature infants, and in many term infants with physiologic stress from unrelated diseases. In addition, newborn 17OHP may be elevated in other forms of CAH, including 11-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase deficiency, and P450 oxidoreductase deficiency. In 21OHD, some of the accumulated intra-adrenal 17OHP is converted to 21-Deoxycortisol (21-deoxy) by 11β-hydroxylase (CYP11B1); 21-deoxy is not elevated in premature infants or in other forms of CAH, and hence is a more specific marker for 21OHD. However, 21-deoxy assays have not been generally available until recently, hence experience is limited. We urge clinical investigators, commercial reference laboratories, and newborn screening programs to investigate replacing 17OHP with 21-deoxy as the analyte of choice for studies of 21OHD.

21-Deoxycortisol is a Key Screening Marker for 21-Hydroxylase Deficiency

J Pediatr 2022 Mar;242:213-219.e1.PMID:34780778DOI:10.1016/j.jpeds.2021.10.063.

Objectives: To assess whether 21-Deoxycortisol (21deoxy) can be used to predict 21-hydroxylase deficiency (21OHD) in newborns and to evaluate the influence of gestational age and the timing of collection on 21deoxy concentrations. Study design: 17-hydroxyprogesterone (17OHP) and 21deoxy levels were measured in 906 newborn screening specimens (851 unaffected newborns, 55 confirmed cases of 21OHD) to compare their ability to identify babies with 21OHD. In addition, these 2 steroids were assessed in the unaffected cohort to determine the influence of gestational age (ranging from 23 to 42 weeks) and the timing of specimen collection on the measured concentrations. Results: The gestational age of the newborn impacted both 17OHP and 21deoxy concentrations, but the degree of influence was more substantial for 17OHP. Timing of collection did not affect 21deoxy concentration. Moreover, 21deoxy was a better predictor of 21OHD status compared with 17OHP, with little overlap in concentrations between the unaffected population and confirmed cases of 21OHD. A streamlined decision tree using solely 21deoxy (cutoff value, 0.85 ng/mL) yielded a 91.7% positive predictive value for 21OHD screening. Conclusions: Our findings demonstrate that 21deoxy is a key disease marker of 21OHD and can be used to improve the accuracy of newborn screening for this disorder.

The High Relevance of 21-Deoxycortisol, (Androstenedione + 17α-Hydroxyprogesterone)/Cortisol, and 11-Deoxycortisol/17α-Hydroxyprogesterone for Newborn Screening of 21-Hydroxylase Deficiency

J Clin Endocrinol Metab 2022 Nov 25;107(12):3341-3352.PMID:36071550DOI:10.1210/clinem/dgac521.

Context: There are limited reports on the detailed examination of steroid profiles for setting algorithms for 21-hydroxylase deficiency (21OHD) screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Objective: We aimed to define an algorithm for newborn screening of 21OHD by LC-MS/MS, measuring a total of 2077 dried blood spot samples in Tokyo. Methods: Five steroids (17α-hydroxyprogesterone [17αOHP], 21-Deoxycortisol [21DOF], 11-deoxycortisol [11DOF], androstenedione [4AD], and cortisol [F]) were included in the panel of LC-MS/MS. Samples from 2 cohorts were assayed: Cohort A, 63 "screening positive" neonates who were referred to an endocrinologist (n = 26 with 21OHD; n = 37 false-positive; obtained from 2015 to 2020); and Cohort B, samples (n = 2014) with 17αOHP values in the 97th percentile or above, in the first-tier test with 17αOHP ELISA from 2020 to 2021. Results: Analysis of Cohort A revealed that the 3 indexes 21DOF, 11DOF/17αOHP, and (4AD + 17αOHP)/F had higher area under the curve (AUC) values (0.999, 0.997, 0.989, respectively), while the 17αOHP AUC was lower (0.970). Accordingly, in addition to 17αOHP, the 3 markers were included for defining the screening algorithm. The assay of Cohort B revealed that the new algorithm gave 92% of predicted positive predictive value without false-negative cases. We also determined the reference values for the 5 steroids at 4 to 7 days after birth, according to sex and gestational age (GA), revealing extremely low levels of 21DOF at any GA irrespective of sex differences. Conclusion: Our study demonstrated the high relevance of 21DOF, (4AD + 17αOHP)/F, and 11DOF/17αOHP, rather than 17αOHP, for 21OHD screening.

21-Deoxycortisol (21-DF) and 17-hydroxyprogesterone (17-OHP) responses to adrenalcorticotropic hormone in males with idiopathic oligozoospermia

Andrologia 1987 May-Jun;19(3):393-7.PMID:2820268DOI:10.1111/j.1439-0272.1987.tb02319.x.

Combined results of 21-DF (via the specific RIA method) and 17-OHP levels in plasma were used to support the evidence that some of the cases with idiopathic oligozoospermia (I.O.) are the result of 21-hydroxylase deficiency (C-21-HD). In our current tests, in four out of 19 males with I.O., elevated levels of 21-DF prior to ACTH stimulation (24.3 +/- 2.3 ng/dl) and after ACTH stimulation (81.2 +/- 5.2 ng/dl) in comparison to the controls (10.6 +/- 4.3 ng/dl and 36.9 +/- 10.1 ng/dl after ACTH) and other I.O. cases were observed. Only one out of these cases presented elevated 17-OHP levels prior and after ACTH stimulation in comparison to the controls and other I.O. cases. Measuring the 21-DF levels along with the 17-OHP in males suspected of C-21-HD, seems to aid the establishing of a correct diagnosis.

Radioimmunoassay for 21-Deoxycortisol: clinical applications

Acta Endocrinol (Copenh) 1985 Apr;108(4):537-44.PMID:2986404DOI:10.1530/acta.0.1080537.

A radioimmunoassay for 21-Deoxycortisol is described. The immunogen, 21-deoxycortisol-3-(0-carboxymethyl) oxime-bovine serum albumin, was prepared, the antisera raised against it were studied and the reliability of the assay was checked. The antiserum selected cross-reacted with 11-deoxycortisol (0.08%), corticosterone (0.25%), cortisol (0.6%) and 17-hydroxyprogesterone (1.6%). 21-Deoxycortisol was separated by celite partition chromatography and eluted in the 70/30 (v/v) isooctane/ethyl acetate fraction together with 11-deoxycortisol and corticosterone. The radioimmunoassay was used to measure 21-Deoxycortisol in the plasma of normal subjects and patients with androgen excess. In normal subjects, men (0.19 ng/ml +/- 0.08) and women (0.18 ng/ml +/- 0.09) had similar basal levels (mean +/- SD). One hour after ACTH stimulation, these levels were increased by a factor of 3.5. In 7 patients treated for classical congenital adrenal hyperplasia associated with 21-hydroxylase deficiency, basal values varied between 9.1 and 39.9 ng/ml (measured at 8 a.m.). In 7 untreated women with late-onset congenital adrenal hyperplasia (with 21-hydroxylase deficiency), ACTH-stimulated levels were increased to between 9 and 25.5 ng/ml. In 14 heterozygous carriers of 21-hydroxylase deficiency, diagnosed by HLA genotyping, all ACTH-stimulated levels were well above the highest corresponding levels in normal subjects, whereas 17-hydroxyprogesterone levels remained within the normal range in 9 of the cases.