Congenital adrenal hyperplasia

New England Journal of Medicine

Volumn 349, Issue 8, 2003, Pages 776-788

  Speiser, Phyllis W ^a,b   White, Perrin C ^c  

^a SCHNEIDER CHILDREN'S HOSPITAL   (United States)

^b NEW YORK UNIVERSITY MEDICAL CENTER   (United States)

^c UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOCORTICOID; MINERALOCORTICOID; HYDROCORTISONE; SODIUM; STEROID;

AUTOSOMAL RECESSIVE DISORDER; CLINICAL FEATURE; CONGENITAL ADRENAL HYPERPLASIA; GENE MUTATION; HETEROZYGOTE; HUMAN; PRENATAL DIAGNOSIS; PRIORITY JOURNAL; REVIEW; SALT LOSING NEPHRITIS; STEROID 21 MONOOXYGENASE DEFICIENCY; VIRILIZATION; ALGORITHM; BIOSYNTHESIS; CONGENITAL MALFORMATION; FEMALE; FEMALE GENITAL SYSTEM; GENETICS; HYPONATREMIA; MALE; METABOLISM; MUTATION;

ADRENAL HYPERPLASIA, CONGENITAL; ALGORITHMS; FEMALE; GENITALIA, FEMALE; HUMANS; HYDROCORTISONE; HYPONATREMIA; MALE; MINERALOCORTICOIDS; MUTATION; PRENATAL DIAGNOSIS; SODIUM; STEROIDS;

EID: 0042466547     PISSN: 00284793     EISSN: None     Source Type: Journal    
DOI: 10.1056/NEJMra021561     Document Type: Review

References (87)

1. White PC, New MI, Dupont B. Congenital adrenal hyperplasia. N Engl J Med 1987;316:1519-24, 1580-6.
2. White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev 2000;21:245-91.
3. Therrell BL. Newborn screening for congenital adrenal hyperplasia. Endocrinol Metab Clin North Am 2001;30:15-30.
4. Speiser PW, Dupont B, Rubinstein P, Piazza A, Kastelan A, New MI. High frequency of nonclassical steroid 21-hydroxylase deficiency. Am J Hum Genet 1985;37:650-67.
5. Fitness J, Dixit N, Webster D, et al. Genotyping of CYP21, linked chromosome 6p markers, and a sex-specific gene in neonatal screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab 1999;84:960-6.
6. Oelkers WK. Effects of estrogens and progestogens on the renin-aldosterone system and blood pressure. Steroids 1996;61:166-71.
7. Lamberts SW, Bruining HA, de Jong FH. Corticosteroid therapy in severe illness. N Engl J Med 1997;337:1285-92.
8. Merke DP, Chrousos GP, Eisenhofer G, et al. Adrenomedullary dysplasia and hypofunction in patients with classic 21-hydroxylase deficiency. N Engl J Med 2000;343:1362-8.
9. Fukushige J, Simomura K, Ueda K. Influence of upright activity on plasma renin activity and aldosterone concentration in children. Eur J Pediatr 1994;153:284-6.
10. Eugster EA, Dimeglio LA, Wright JC, et al. Height outcome in congenital adrenal hyperplasia caused by 21-hydroxylase deficiency: a meta-analysis. J Pediatr 2001;138:26-32.
11. Jaaskelainen J, Voutilainen R. Growth of patients with 21-hydroxylase deficiency: an analysis of the factors influencing adult height. Pediatr Res 1997;41:30-3.
12. Yu AC, Grant DB. Adult height in women with early-treated congenital adrenal hyperplasia (21-hydroxylase type): relation to body mass index in earlier childhood. Acta Paediatr 1995;84:899-903.
13. Barnes RB, Rosenfield RL, Ehrmann DA, et al. Ovarian hyperandrogynism as a result of congenital adrenal virilizing disorders: evidence for perinatal masculinization of neuroendocrine function in women. J Clin Endocrinol Metab 1994;79:1328-33.
14. Deneux C, Tardy V, Dib A, et al. Phenotype-genotype correlation in 56 women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 2001;86:207-13.
15. Mulaikal RM, Migeon CJ, Rock JA. Fertility rates in female patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. N Engl J Med 1987;316:178-82.
16. Wilson JD. The role of androgens in male gender role behavior. Endocr Rev 1999;20:726-37.
17. Meyer-Bahlburg HF. Gender and sexuality in classic congenital adrenal hyperplasia. Endocrinol Metab Clin North Am 2001;30:155-71.
18. Lo JC, Grumbach MM. Pregnancy outcomes in women with congenital virilizing adrenal hyperplasia. Endocrinol Metab Clin North Am 2001;30:207-29.
19. Premawardhana LD, Hughes IA, Read GF, Scanlon MF. Longer term outcome in females with congenital adrenal hyperplasia (CAH): the Cardiff experience. Clin Endocrinol (Oxf) 1997;46:327-32.
20. Urban MD, Lee PA, Migeon CJ. Adult height and fertility in men with congenital virilizing adrenal hyperplasia. N Engl J Med 1978;299:1392-6.
21. Cabrera MS, Vogiatzi MG, New MI. Long term outcome in adult males with classic congenital adrenal hyperplasia. J Clin Endocrinol Metab 2001;86:3070-8.
22. Stikkelbroeck NM, Otten BJ, Pasic A, et al. High prevalence of testicular adrenal rest tumors, impaired spermatogenesis, and Leydig cell failure in adolescent and adult males with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2001;86:5721-8.
23. Srikanth MS, West BR, Ishitani M, Isaacs H Jr, Applebaum H, Costin G. Benign testicular tumors in children with congenital adrenal hyperplasia. J Pediatr Surg 1992;27:639-41.
24. Murphy H, George C, de Kretser D, Judd S. Successful treatment with ICSI of infertility caused by azoospermia associated with adrenal rests in the testes: case report. Hum Reprod 2001;16:263-7.
25. Walker BR, Skoog SJ, Winslow BH, Canning DA, Tank ES. Testis sparing surgery for steroid unresponsive testicular tumors of the adrenogenital syndrome. J Urol 1997;157:1460-3.
26. Balsamo A, Cacciari E, Piazzi S, et al. Congenital adrenal hyperplasia: neonatal mass screening compared with clinical diagnosis only in the Emilia-Romagna region of Italy, 1980-1995. Pediatrics 1996;98:362-7.
27. Tajima T, Fujieda K, Nakae J, et al. Molecular basis of nonclassical steroid 21-hydroxylase deficiency detected by neonatal mass screening in Japan. J Clin Endocrinol Metab 1997;82:2350-6.
28. Therrell BL Jr, Berenbaum SA, Manter-Kapanke V, et al. Results of screening 1.9 million Texas newborns for 21-hydroxylase-deficient congenital adrenal hyperplasia. Pediatrics 1998;101:583-90.
29. Moran C, Azziz R, Carmina E, et al. 21-Hydroxylase-deficient nonclassical adrenal hyperplasia is a progressive disorder: a multicenter study. Am J Obstet Gynecol 2000;183:1468-74.
30. Knochenhauer ES, Cortet-Rudelli C, Cunnigham RD, Conway-Myers BA, Dewailly D, Azziz R. Carriers of 21-hydroxylase deficiency are not at increased risk for hyperandrogenism. J Clin Endocrinol Metab 1997;82:479-85.
31. Ohkubo S, Shimozawa K, Matsumoto M, Kitagawa T. Analysis of blood spot 17 alpha-hydroxyprogesterone concentration in premature infants - proposal for cut-off limits in screening for congenital adrenal hyperplasia. Acta Paediatr Jpn 1992;34:126-33.
32. Cutfield WS, Webster D. Newborn screening for congenital adrenal hyperplasia in New Zealand. J Pediatr 1995;126:118-21.
33. Allen DB, Hoffman GL, Fitzpatrick P, Laessig R, Maby S, Slyper A. Improved precision of newborn screening for congenital adrenal hyperplasia using weight-adjusted criteria for 17-hydroxyprogesterone levels. J Pediatr 1997;130:128-33.
34. Gruneiro-Papendieck L, Prieto L, Chiesa A, Bengolea S, Bossi G, Bergada C. Neonatal screening program for congenital adrenal hyperplasia: adjustments to the recall protocol. Horm Res 2001;55:271-7.
35. Mikami A, Fukushi M, Oda H, Fujita K, Fujieda K. Newborn screening for congenital adrenal hyperplasia in Sapporo City: sixteen years experience. Southeast Asian J Trop Med Public Health 1999;30:Suppl 2:100-2.
36. Boudi A, Giton F, Galons H, et al. Development of a plasma 17alpha-hydroxyprogesterone time resolved-fluorescence immunoassay involving a new biotinylated tracer. Steroids 2000;65:103-8.
37. Minutti C, Magera MJ, Casetta BN, Zimmerman D, Rinaldo P, Matern D. Analysis of 17-OH progesterone (17OHP) by tandem mass spectrometry (MS/MS) for the detection of congenital adrenal hyperplasia (CAH) in newborn blood spots. J Inherit Metab Dis 2001;24:Suppl 1:10. abstract.
38. Zarkovic M, Ciric J, Stojanovic M, et al. Optimizing the diagnostic criteria for standard (250-microg) and low dose (1-microg) adrenocorticotropin tests in the assessment of adrenal function. J Clin Endocrinol Metab 1999;84:3170-3.
39. New MI, Lorenzen F, Lerner AJ, et al. Genotyping steroid 21-hydroxylase deficiency: hormonal reference data. J Clin Endocrinol Metab 1983;57:320-6.
40. Fiet J, Gueux B, Gourmelen M, et al. Comparison of basal and adrenocorticotropin-stimulated plasma 21-deoxycortisol and 17-hydroxyprogesterone values as biological markers of late-onset adrenal hyperplasia. J Clin Endocrinol Metab 1988;66:659-67.
41. Nordenstrom A, Thilen A, Hagenfeldt L, Larsson A, Wedell A. Genotyping is a valuable diagnostic complement to neonatal screening for congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. J Clin Endocrinol Metab 1999;84:1505-9.
42. Tajima T, Fujieda K, Nakae J, Mikami A, Cutler GB Jr. Mutations of the CYP21 gene in nonclassical steroid 21-hydroxylase deficiency in Japan. Endocr J 1998;45:493-7.
43. Day DJ, Speiser PW, White PC, Barany F. Detection of steroid 21-hydroxylase alleles using gene-specific PCR and a multiplexed ligation detection reaction. Genomics 1995;29:152-62.
44. Higashi Y, Yoshioka H, Yamane M, Gotoh O, Fujii-Kuriyama Y. Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: a pseudogene and a genuine gene. Proc Natl Acad Sci U S A 1986;83:2841-5.
45. White PC, New MI, Dupont B. Structure of human steroid 21-hydroxylase genes. Proc Natl Acad Sci U S A 1986;83:5111-5.
46. White PC, Vitek A, Dupont B, New MI. Characterization of frequent deletions causing steroid 21-hydroxylase deficiency. Proc Natl Acad Sci U S A 1988;85:4436-40.
47. Cytochrome P450, subfamily XXIA (steroid 21-hydroxylase, congenital adrenal hyperplasia), polypeptide 2. Cardiff, Wales: Human Gene Mutation Database. 2003. (Accessed July 25, 2003, at http://archive.uwcm.ac.uk/uwcm/mg/search/120605.html.)
48. Cargill M, Altshuler D, Ireland J, et al. Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet 1999;22:231-8.
49. Tusie-Luna MT, White PC. Gene conversions and unequal crossovers between CYP21 (steroid 21-hydroxylase gene) and CYP21P involve different mechanisms. Proc Natl Acad Sci U S A 1995;92:10796-800.
50. 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;90:584-95.
51. Higashi Y, Hiromasa T, Tanae A, et al. Effects of individual mutations in the P-450(C21) pseudogene on the P-450(C21) activity and their distribution in the patient genomes of congenital steroid 21-hydroxylase deficiency. J Biochem (Tokyo) 1991;109:638-44.
52. Mornet E, Crete P, Kuttenn F, et al. Distribution of deletions and seven point mutations on CYP21B genes in three clinical forms of steroid 21-hydroxylase deficiency. Am J Hum Genet 1991;48:79-88.
53. Owerbach D, Crawford YM, Draznin MB. Direct analysis of CYP21B genes in 21-hydroxylase deficiency using polymerase chain reaction amplification. Mol Endocrinol 1990;4:125-31.
54. Wedell A, Thilen A, Ritzen EM, Stengler B, Luthman H. Mutational spectrum of the steroid 21-hydroxylase gene in Sweden: implications for genetic diagnosis and association with disease manifestation. J Clin Endocrinol Metab 1994;78:1145-52.
55. Wilson RC, Mercado AB, Cheng KC, New MI. Steroid 21-hydroxylase deficiency: genotype may not predict phenotype. J Clin Endocrinol Metab 1995;80:2322-9.
56. Higashi Y, Tanae A, Inoue H, Hiromasa T, Fujii-Kuriyama Y. Aberrant splicing and missense mutations cause steroid 21-hydroxylase [P-450(C21)] deficiency in humans: possible gene conversion products. Proc Natl Acad Sci U S A 1988;85:7486-90.
57. Tusie-Luna MT, Traktman P, White PC. Determination of functional effects of mutations in the steroid 21-hydroxylase gene (CYP21) using recombinant vaccinia virus. J Biol Chem 1990;265:20916-22.
58. Tusie-Luna MT, Speiser PW, Dumic M, New MI, White PC. A mutation (Pro-30 to Leu) in CYP21 represents a potential non-classic steroid 21-hydroxylase deficiency allele. Mol Endocrinol 1991;5:685-92.
59. Amor M, Parker KL, Globerman H, New MI, White PC. Mutation in the CYP21B gene (Ile-172→Asn) causes steroid 21-hydroxylase deficiency. Proc Natl Acad Sci U S A 1988;85:1600-4.
60. Speiser PW, New MI. Genotype and hormonal phenotype in nonclassical 21-hydroxylase deficiency. J Clin Endocrinol Metab 1987;64:86-91.
61. Scriver CR, Waters PJ. Monogenic traits are not simple: lessons from phenylketonuria. Trends Genet 1999;15:267-72.
62. Dipple KM, McCabe ER. Phenotypes of patients with "simple" Mendelian disorders are complex traits: thresholds, modifiers, and systems dynamics. Am J Hum Genet 2000;66:1729-35.
63. Day DJ, Speiser PW, Schulze E, et al. Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees. Hum Mol Genet 1996;5:2039-48.
64. Metzger DL, Wright NM, Veldhuis JD, Rogol AD, Kerrigan JR. Characterization of pulsatile secretion and clearance of plasma cortisol in premature and term neonates using deconvolution analysis. J Clin Endocrinol Metab 1993;77:458-63.
65. Kerrigan JR, Veldhuis JD, Leyo SA, Iranmanesh A, Rogol AD. Estimation of daily cortisol production and clearance rates in normal pubertal males by deconvolution analysis. J Clin Endocrinol Metab 1993;76:1505-10.
66. Migeon CJ, Wisniewski AB. Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency: growth, development, and therapeutic considerations. Endocrinol Metab Clin North Am 2001;30:193-206.
67. Schnitzer JJ, Donahoe PK. Surgical treatment of congenital adrenal hyperplasia. Endocrinol Metab Clin North Am 2001;30:137-54.
68. Creighton SM, Minto CL, Steele SJ. Objective cosmetic and anatomical outcomes at adolescence of feminising surgery for ambiguous genitalia done in childhood. Lancet 2001;358:124-5.
69. Speiser PW. Congenital adrenal hyperplasia: transition from childhood to adulthood. J Endocrinol Invest 2001;24:681-91.
70. New MI, Carlson A, Obeid J, et al. Prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies. J Clin Endocrinol Metab 2001;86:5651-7.
71. Pang SY, Pollack MS, Marshall RN, Immken L. Prenatal treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. N Engl J Med 1990;322:111-5.
72. Chin D, Speiser PW, Imperato-McGinley J, et al. Study of a kindred with classic congenital adrenal hyperplasia: diagnostic challenge due to phenotypic variance. J Clin Endocrinol Metab 1998;83:1940-5.
73. Seckl JR, Miller WL. How safe is long-term prenatal glucocorticoid treatment? JAMA 1997;277:1077-9.
74. Newnham JP. Is prenatal glucocorticoid administration another origin of adult disease? Clin Exp Pharmacol Physiol 2001;28:957-61.
75. Pang S, Clark AT, Freeman LC, et al. Maternal side effects of prenatal dexamethasone therapy for fetal congenital adrenal hyperplasia. J Clin Endocrinol Metab 1992;75:249-53.
76. Clayton PE, Miller WL, Oberfield SE, Ritzen EM, Sippell WG, Speiser PW. Consensus statement on 21-hydroxylase deficiency from the Lawson Wilkins Pediatric Endocrine Society and The European Society for Pediatric Endocrinology. J Clin Endocrinol Metab 2002;87:4048-53.
77. Idem. Consensus statement on 21-hydroxylase deficiency from the European Society for Pediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society. Horm Res 2002;58:188-95.
78. Merke DP, Keil MF, Jones JV, Fields J, Hill S, Cutler GB Jr. Flutamide, testolactone, and reduced hydrocortisone dose maintain normal growth velocity and bone maturation despite elevated androgen levels in children with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2000;85:1114-20.
79. Merke DP, Bornstein SR, Avila NA, Chrousos GP. Future directions in the study and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Ann Intern Med 2002;136:320-34.
80. Quintos JB, Vogiatzi MG, Harbison MD, New MI. Growth hormone therapy alone or in combination with gonadotropin-releasing hormone analog therapy to improve the height deficit in children with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2001;86:1511-7.
81. Gunther DF, Bukowski TP, Ritzen EM, Wedell A, Van Wyk JJ. Prophylactic adrenalectomy of a three-year-old girl with congenital adrenal hyperplasia: pre- and postoperative studies. J Clin Endocrinol Metab 1997;82:3324-7.
82. Gmyrek GA, New MI, Sosa RE, Poppas DP. Bilateral laparoscopic adrenalectomy as a treatment for classic congenital adrenal hyperplasia attributable to 21-hydroxylase deficiency. Pediatrics 2002;109:E28.
83. Meyers RL, Grua JR. Bilateral laparoscopic adrenalectomy: a new treatment for difficult cases of congenital adrenal hyperplasia. J Pediatr Surg 2000;35:1586-90.
84. Warinner SA, Zimmerman D, Thompson GB, Grant CS. Study of three patients with congenital adrenal hyperplasia treated by bilateral adrenalectomy. World J Surg 2000;24:1347-52.
85. Van Wyk JJ, Gunther DF, Ritzen EM, et al. The use ofadrenalectomy as a treatment for congenital adrenal hyperplasia. J Clin Endocrinol Metab 1996;81:3180-90.
86. Hunt PJ, Gurnell EM, Huppert FA, et al. Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison's disease in a randomized, double blind trial. J Clin Endocrinol Metab 2000;85:4650-6.
87. Tajima T, Okada T, Ma XM, Ramsey W, Bornstein S, Aguilera G. Restoration of adrenal steroidogenesis by adenovirus-mediated transfer of human cytochrome P450 21-hydroxylase into the adrenal gland of 21-hydroxylase-deficient mice. Gene Ther 1999;6:1898-903.