Zona fasciculata 21-hydroxysteroids and precursor-to-product ratios in 21-hydroxylase deficiency: Further characterization of classic and non-classic patients and heterozygote carriers

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• 作者：F. A. Costa-Barbosa ; V. M. Carvalho…
• 关键词：21 ; deoxycortisol (21DF) ; 17 ; hydroxyprogesterone (17OHP) ; 11 ; deoxycortisol (S) ; 11 ; deoxycorticosterone (DOC) ; corticosterone (B) ; 21 ; hydroxylase deficiency (21OHD) ; 21OHD carriers ; precursor ; to ; product ratios ; wild ; type (WT)
• 刊名：Journal of Endocrinological Investigation
• 出版年：2011
• 出版时间：September 2011
• 年：2011
• 卷：34
• 期：8
• 页码：587-592
• 全文大小：
• 参考文献：1.Bartter F. Adrenogenital syndromes from physiology to chemistry. In: Lee PA, Plotnick LP, Kowarski AA, Migeon C, eds. Congenital adrenal hyperplasia. 1st ed. Baltimore: University Park Press. 1977, 9鈥?9.
  2.White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev 2000, 21: 245鈥?1.PubMed
  3.Speiser PW, White PC. Congenital adrenal hyperplasia. N Engl J Med 2003, 349: 776鈥?8.PubMed CrossRef
  4.Forest MG. Recent advances in the diagnosis and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Hum Reprod Update 2004, 10: 469鈥?5.PubMed CrossRef
  5.Tonetto-Fernandes V, Lemos-Marini S, Kuperman H, Ribeiro-Neto LM, Verreschi ITN, Kater CE. Serum 21-deoxycortisol, 17-hydrox-yprogesterone, and 11 -deoxycortisol in classic congenital adrenal hyperplasia: clinical and hormonal correlations and identification of patients with 11 beta-hydroxylase deficiency among a large group with alleged 21-hydroxylase deficiency. J Clin Endocrinol Metab 2006, 91: 2179鈥?4.PubMed CrossRef
  6.Fiet J, Gueux B, Gourmelen M, et al. Comparison of basal and adrenocoticotropin- stimulated plasma 21-deoxycortisol and 17-hydroxyprogesterone values as biological markers of late-onset adrenal hyperplasia. J Clin Endocrinol Metab 1988, 66: 659鈥?7.PubMed CrossRef
  7.Biglieri EG, Kater CE. Mineralocorticoids in congenital adrenal hyperplasia. J Steroid Biochem Mol Biol 1991, 40: 493鈥?.PubMed CrossRef
  8.Kater CE, Biglieri EG, Wajchenberg B. Effects of continued adrenocorticotropin stimulation on the mineralocorticoid hormones in classical and nonclassical simple virilizing types of 21 -hydroxylase deficiency. J Clin Endocrinol Metab 1985, 60: 1057鈥?2.PubMed CrossRef
  9.Speiser PW, Dupont J, Zhu D, et al. Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21- hydroxylase deficiency. J Clin Invest 1992, 90: 584鈥?5.PubMed Central PubMed CrossRef
  10.Bachega TA, Billerbeck AE, Marcondes JA, Madureira G, Arnhold IJ, Mendonca BB. Influence of different genotypes on 17-hydroxyprogesterone levels in patients with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency Clin Endocrinol 2000, 52: 601鈥?.CrossRef
  11.Azziz R, Dewailly D, Owerbach D. Nonclassic adrenal hyperplasia: current concepts. J Clin Endocrinol Metab 1994, 78: 810鈥?.PubMed
  12.Azziz R, Dewailly D. Diagnosis, screening, and treatment of non-classic 21 -hydroxylase deficiency. In: Azziz R, Nestler JE, Dewailly eds. Androgen excess disorders in women, 1st ed. Lippincott-Raven: Philadelphia. 1997, 181鈥?2.
  13.New MI. Extensive clinical experience: Nonclassical 21-hydroxylase deficiency. J Clin Endocrinol Metab 2006, 91: 4205鈥?4.PubMed CrossRef
  14.Pardini DP, Kater CE, Vieira JG, Biglieri EG. Impaired mineralocorticoid hormone responses to adrenocorticotropin stimulation: additional characterization of heterozigozity for the 21 鈥?hydroxylase deficiency type of congenital adrenal hyperplasia. J Clin Edocrinol Metab 1983, 57: 1061鈥?.CrossRef
  15.Peter M, Sippell WG, Lorenzen F, Willig R, Westphal E, Grosse-Wilde H. Improved test to identify heterozygotes for congenital adrenal hyperplasia without index case examination. Lancet 1990, 335: 1296鈥?.PubMed CrossRef
  16.Carvalho VM, Nakamura OH, Vieira JG. Simultaneous quantitation of seven endogenous C-21 adrenal steroids by liquid chromatography tandem mass spectrometry in human serum. J Chromatrogr B Analyt Technol Biomed Life Sci 2008, 872: 154鈥?1.CrossRef
  17.Hornsby PJ. Regulation of 21-hydroxylase activity by steroids in cultured bovine adrenocortical cells: possible significance for adrenocortical androgen synthesis. Endocrinology 1982, 111: 1092鈥?01.PubMed CrossRef
  18.Kater CE, Czepielewski MA, Biglieri EG. Androgen- and estrogen-producing adrenocortical tumors causing hypertension. In: Biglieri EG & Melby JC eds. Endocrine Hypertension, 1st ed. New York: Raven Press. 1990, 195鈥?06.
  19.Winkel CA, Simpson ER, Milewich L, MacDonald PC. Deoxycorticosterone biosynthesis in human kidney: potential for formation of a potent mineralocorticosteroid in its site of action. Proc Natl Acad Sci U S A 1980, 77: 7069鈥?3.PubMed Central PubMed CrossRef
  20.Casey ML, Winkel CA, MacDonald PC. Conversion of progesterone to deoxycorticosterone in the human fetus: steroid 21-hydroxylase activity in fetal tissues. J Steroid Biochem 1983, 18: 449鈥?2.PubMed CrossRef
  21.Franklin SO, Lieberman S, Greenfield NJ. Further evidence that there is more than one adrenal 21 hydroxylase system. J Steroid Biochem 1987, 28: 749鈥?7.PubMed CrossRef
  22.Mellon SH, Miller WL. Extraadrenal steroid 21-hydroxylation is not mediated by P450c21. J Clin Invest 1989, 84: 1497鈥?02.PubMed Central PubMed CrossRef
  23.Biglieri EG, Wajchenberg BL, Malerbi DA, Okada H, Leme CE, Kater CE. The zonal origins of the mineralocorticoid hormones in the 21-hydroxylation deficiency of congenital adrenal hyperplasia. J Clin Endocrinol Metab 1981, 53: 964鈥?.PubMed CrossRef
  24.Antonipillai I, Moghissi E, Frasier SD, Horton R. The origin of plasma deoxycorticosterone in the syndrome of congenital adrenal hyperplasia and acute states of adrenocorticotropin excess. J Clin Edocrinol Metab 1983, 57: 580鈥?.CrossRef
  25.Wajchenberg BL, Biglieri EG, Okada H, Malerbi DA, Achando SS, Kater CE. Supression and stimulation of mineralocorticoid hormones (MCH) in the simple virilizing form of congenital adrenal hyperplasia (CAH) evaluated by the quantitation in adrenal venous blood. J Steroid Biochem 1983, 19: 655鈥?1.PubMed CrossRef
  26.Speiser PW, Agdere L, Ueshiba H, White PC, New MI. Aldosterone synthesis in salt- wasting congenital adrenal hyperplasia with complete absence of adrenal 21 -hydroxylase. N Engl J Med 1991, 324: 145鈥?.PubMed CrossRef
  27.Koppens PF, Hoogenboezem T, Drop SL, de Muinck-Keizer-Schrama SM, Degenhart HJ. Aldosterone production despite absence or defectiveness of the CYP21 genes in two patients with salt-losing congenital adrenal hyperplasia caused by steroid 21-hydroxylase deficiency. Clin Endocrinol 1998, 49: 815鈥?2.CrossRef
  28.Yamazaki H, Shimada T. Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9 and 3A4 inhuman liver microsomes. Arch Biochem Biophys 1997, 346: 161鈥?.PubMed CrossRef
  29.Gomes LG, Huang N, Agrawal V, Mendon莽a BB, Bachega TA, Miller WL. Extraadrenal 21 -hydroxylation by CYP2C19 and CYP3A4: effect on 21- hydroxylase deficiency. J Clin Endocrinol Metab 2009, 94: 89鈥?5.PubMed Central PubMed CrossRef
  30.Bidet M, Bellann茅-Chantelot C, Galand-Portier MB, et al. Clinical and molecular characterization of a cohort of 161 unrelated women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency and 330 family members. J Clin Endocrinol Metab 2009, 94: 1570鈥?.PubMed CrossRef
  31.Tardy V, Forest M, De Rougemont A, Morel Y. Detection of heterozygotes for 21 -hydroxylase deficiency: Validation of 21 -deoxycortisol after ACTH test by sequencing of the entire CYP21 gene. Horm Res 2005, 64(Suppl 1): S41鈥?.
  32.Costa-Barbosa FA, Tonetto-Fernandes VF, Carvalho VM, et al. Superior discriminating value of ACTH-stimulated serum 21-deoxycortisol in identifying heterozygote carriers for 21-hydroxylase deficiency. Clin Endocrinol (Oxf) 2010, 73: 700鈥?.CrossRef
  33.Nelson EB, Bryan GT. Steroid hydroxylations by human adrenal cortex microsomes 1,2. J Clin Endocrinol Metab 1975, 41: 7鈥?2.PubMed CrossRef
  34.Barbaro M, Lajic S, Baldazzi L, Balsamo A, Pirazzoli P, Cicognani A, Wedell A, Cacciari E. Functional Analysis of Two Recurrent Amino Acid Substitutions in the CYP21 Gene from Italian Patients with Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab 2004, 89: 2402鈥?.PubMed CrossRef
  
• 作者单位：F. A. Costa-Barbosa (1)
  V. M. Carvalho (2)
  O. H. Nakamura (2)
  T. A. S. S. Bachega (3)
  J. G. H. Vieira (1) (2)
  C. E. Kater (1)
  
  1. Steroids Laboratory, Adrenal and Hypertension Unit, Division of Endocrinology, Department of Medicine, Federal University of S茫o Paulo, UNIFESP-EPM, Rua Pedro de Toledo, 781 - 13o. andar, 04039-032, S茫o Paulo, SP, Brazil
  2. Fleury Institute, S茫o Paulo, SP, Brazil
  3. Endocrinology and Development Unit, Division of Endocrinology (LIM-42) Hospital das Cl铆nicas, University of S茫o Paulo School of Medicine, S茫o Paulo, SP, Brazil
  
• 刊物类别：Medicine/Public Health, general; Endocrinology; Metabolic Diseases;
• 刊物主题：Medicine/Public Health, general; Endocrinology; Metabolic Diseases;
• 出版者：Springer International Publishing
• ISSN：1720-8386

文摘

Introduction: Although much is known about the increased levels of the 21-hydroxylase substrates 17-hydroxyprogesterone (17OHP) and 21-deoxycortisol (21 DF) 鈥?the biochemical markers of all forms of 21-hydroxylase deficiency (21OHD), only limited information is available on the zona fasciculata (ZF) products distal to the enzymatic block: 11 -deoxycortisol (S), 11 -deoxycorticosterone (DOC), and corticosterone (B). Objective: To investigate whether basal and post-ACTH levels of S, DOC, and B and the 21 -hydroxylase precursor-to-product ratios determined by tandem mass spectrometry preceded by high-performance liquid chromatography separation (liquid chromatography-tandem mass spectrometry) could disclose distinct profiles in genotypically confirmed classic (no.=14) and non-classic (NC) (no.=18) patients, heterozygote carriers (no.=61) and wild-types (WT) (no.=27) for 21OHD. Results: Salt wasting (SW) and simple virilizing (SV) had higher basal levels of DOC with no further increase in response to ACTH. Stimulated DOC was similar in 21OHD patients and carriers but was reduced as compared to WT. ACTH-stimulated B increased gradually from SW and SV through WT. The post-ACTH 21DF/B ratio was able to detect 92% of the carriers among WT. All NC patients could be detected by post-ACTH 17OHP/DOC and 21 DF/B, with no overlap with 21OHD carriers. Conclusion: Although 21-hydroxylase is a key enzymatic step in both 17-hydroxy and 17-deoxy pathways of ZF, the reaction is mostly affected in the latter pathway, leading to a significant impairment of B production, which may further characterize the 21OHD subtypes. Also, the precursor-to-product ratios, particularly 21 DF/B, can demonstrate the distinctive outline of 21OHD subtypes, including carriers and normal subjects. Key-words 21-deoxycortisol (21DF) 17-hydroxyprogesterone (17OHP) 11-deoxycortisol (S) 11-deoxycorticosterone (DOC) corticosterone (B) 21-hydroxylase deficiency (21OHD) 21OHD carriers precursor-to-product ratios wild-type (WT)