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Congenital Adrenal Hyperplasia

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Pediatric Endocrinology

Abstract

Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders in which there is a deficiency of one of the enzymes necessary for cortisol synthesis. An abnormality in each of the enzymatic activities required for cortisol synthesis has been described. As a result of the disordered enzymatic step, there is decreased cortisol synthesis, increased ACTH via a negative feedback system, overproduction of the hormones prior to the enzymatic step or not requiring the deficient enzyme, and deficiency of the hormones distal to the disordered enzymatic step. Since several of the enzymatic steps are required for sex hormone synthesis by the gonad, a disordered enzymatic step in the gonad resulting in gonadal steroid hormone deficiency may also be present. This chapter presents an overview of all of the enzymatic deficiencies resulting in CAH with the most extensive review of 21-hydroxylase deficiency which is the most common, first described, and most intensively studied of the enzymatic disorders.

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References

  1. Levine LS. Congenital adrenal hyperplasia. Pediatr Rev. 2000;21:159–70.

    Article  CAS  PubMed  Google Scholar 

  2. Grumbach MM, Conte FA. Disorders of sex differentiation. In: Wilson JD, editor. Williams textbook of endocrinology. 9th ed. Philadelphia: Saunders; 1998. p. 1361–74.

    Google Scholar 

  3. Pang S. Congenital adrenal hyperplasia. Endocrinol Metab Clin N Am. 1997;26:853–91.

    Article  CAS  Google Scholar 

  4. Miller WL. Molecular biology of steroid hormone synthesis. Endocr Rev. 1998;9:295–318.

    Article  Google Scholar 

  5. White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev. 2000;21:245–91.

    CAS  PubMed  Google Scholar 

  6. New MI. Diagnosis and management of congenital adrenal hyperplasia. Annu Rev Med. 1998;49:311–28.

    Article  CAS  PubMed  Google Scholar 

  7. Bose HS, Sugawara T, Strauss JF III, et al. The pathophysiology and genetics of lipoid adrenal hyperplasia. N Engl J Med. 1996;355:1870–8.

    Article  Google Scholar 

  8. Miller WL. Disorders in the initial steps of steroid hormone synthesis. J Steroid Biochem Mol Biol. 2017;165:18–37.

    Article  CAS  PubMed  Google Scholar 

  9. Miller WL. Androgen biosynthesis from cholesterol to DHEA. Mol Cell Endocrinol. 2002;198(1–2):7–14.

    Article  CAS  PubMed  Google Scholar 

  10. Jean A, Mansukhani M, Oberfield SE, et al. Prenatal diagnosis of congenital lipoid adrenal hyperplasia (CLAH) by estriol amniotic fluid analysis and molecular genetic testing. Prenat Diagn. 2008;28(1):11–4.

    Article  CAS  PubMed  Google Scholar 

  11. Kim CJ. Congenital lipoid adrenal hyperplasia. Ann Pediatr Endocrinol Metab. 2014;19(4):179–83.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Abdulhadi-Atwan M, Jean A, Chung WK, et al. Role of a founder c.201_202delCT mutation and new phenotypic features of congenital lipoid adrenal hyperplasia in Palestinians. J Clin Endocrinol Metab. 2007;92(10):4000–8. [Epub 2007 Jul 31].

    Article  CAS  PubMed  Google Scholar 

  13. Saenger P, Klonari Z, Black SM, et al. Prenatal diagnosis of congenital lipoid adrenal hyperplasia. J Clin Endocrinol Metab. 1995;80:200–5.

    CAS  PubMed  Google Scholar 

  14. Bens S, Mohn A, Yüksel B, et al. Congenital lipoid adrenal hyperplasia: functional characterization of three novel mutations in the STAR gene. J Clin Endocrinol Metab. 2010;95(3):1301–8.

    Article  CAS  PubMed  Google Scholar 

  15. Sahakitrungruang T, Soccio R, Lang-Muritano M, et al. Clinical, genetic, and functional characterization of four patients carrying partial loss-of-function mutations in the steroidogenic acute regulatory protein (StAR). J Clin Endocrinol Metab. 2010;95(7):3352–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Tajima T, Fujieda K, Kouda N, et al. Heterozygous mutation in the cholesterol side chain cleavage enzyme (P450scc) gene in a patient with 46, XY sex reversal and adrenal insufficiency. J Clin Endocrinol Metab. 2001;86:3820–5.

    Article  CAS  PubMed  Google Scholar 

  17. Katsumata N, Ohtake M, Hojo T, et al. Compound heterozygous mutations in the cholesterol side-chain cleavage enzyme gene (CYP11A) cause congenital adrenal insufficiency in humans. J Clin Endocrinol Metab. 2002;87:3808–13.

    Article  CAS  PubMed  Google Scholar 

  18. Miller WL. Congenital lipoid adrenal hyperplasia: the human gene knockout for the steroidogenic acute regulatory protein. J Mol Endocrinol. 1997;19:227–40.

    Article  CAS  PubMed  Google Scholar 

  19. Fujieda K, Tajima T, Nakae J, et al. Spontaneous puberty in 46,XX subjects with congenital lipoid adrenal hyperplasia. J Clin Invest. 1997;99:1265–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bose HS, Sato S, Aisenberg J, et al. Mutations in the steroidogenic acute regulatory protein (StAR) in six patients with congenital lipoid adrenal hyperplasia. J Clin Endocrinol Metab. 2000;85:3636–9.

    CAS  PubMed  Google Scholar 

  21. Scott RR, Miller WL. Genetic and clinical features of P450 oxidoreductase deficiency. Horm Res. 2008;69:266–75.

    Article  CAS  PubMed  Google Scholar 

  22. Kaur J, Casas L, Bose HS. Lipoid congenital adrenal hyperplasia due to STAR mutations in a Caucasian patient. Endocrinol Diabetes Metab Case Rep. 2016;2016:150119. Epub 2016 Mar 2.

    PubMed  PubMed Central  Google Scholar 

  23. Huang Z, Ye J, Han L, Qiu W, Zhang H, Yu Y, Liang L, Gong Z, Gu X. Identification of five novel STAR variants in ten Chinese patients with congenital lipoid adrenal hyperplasia. Steroids. 2016;108:85–91. Epub 2016 Jan 28.

    Article  CAS  PubMed  Google Scholar 

  24. Baquedano MS, Guercio G, Marino R, Berensztein E, Costanzo M, Ramirez P, Bailez M, Vaiani E, Maceiras M, Rivarola MA, Belgorosky A. Novel heterozygous mutation in the steroidogenic acute regulatory protein gene in a 46,XY patient with congenital lipoid adrenal hyperplasia. Medicina (B Aires). 2013;73(4):297–302.

    CAS  Google Scholar 

  25. Yuksel B, Kulle AE, Gurbuz F, Welzel M, Kotan D, Mengen E, Holterhus PM, Topaloglu AK, Grotzinger J, Riepe FG. The novel mutation p.Trp147Arg of the steroidogenic acute regulatory protein causes classic lipoid congenital adrenal hyperplasia with adrenal insufficiency and 46, XY disorder of sex development. Horm Res Paediatr. 2013;80:163–9.

    Article  PubMed  CAS  Google Scholar 

  26. Simard J, Ricketts ML, Gingras S, Soucy P, Feltus FA, Melner MH. Molecular biology of the 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase gene family. Endocr Rev. 2005;26(4):525–82. [Epub 2005 Jan 4].

    Article  CAS  PubMed  Google Scholar 

  27. Benkert AR, Young M, Robinson D, Hendrickson C, Lee PA, Strauss KA. Severe salt-losing 3β-hydroxysteroid deydrogenase deficiency: treatment and outcomes of HSD3B2 c.35G>A homozygotes. J Clin Endocrinol Metab. 2015;100:E1105–15.

    Article  Google Scholar 

  28. Simard J, Moisan AM, Morel Y. Congenital adrenal hyperplasia due to 3β(beta)-hydroxysteroid dehydrogenase/Δ(delta)5-Δ(delta)4 isomerase deficiency. Semin Reprod Med. 2002;20(3):255–76.

    Article  CAS  PubMed  Google Scholar 

  29. Simard J, Rhéaume E, Sanchez R, et al. Molecular basis of congenital adrenal hyperplasia due to 3β(beta)-hydroxysteroid deficiency. Mol Endocrinol. 1993;7:716–28.

    CAS  PubMed  Google Scholar 

  30. Mason JI. The 3β(beta)-hydroxysteroid dehydrogenase gene family of enzymes. Trends Endocrinol Metab. 1993;6:199.

    Article  Google Scholar 

  31. Chang YT, Zhang L, Alkaddour HS, et al. Absence of molecular defect in the Type II 3β(beta)-hydroxysteroid dehydrogenase (3β(beta)-HSD) gene in premature pubarche children and hirsute female patients with moderately decreased adrenal 3β(beta)-HSD activity. Pediatr Res. 1995;37:820–4.

    Article  CAS  PubMed  Google Scholar 

  32. Pang S. Genetics of 3β(beta)-hydroxysteroid dehydrogenase deficiency disorder. Growth Genet Horm. 1996;12:5–9.

    Google Scholar 

  33. Moisan AM, Ricketts ML, Tardy V, et al. New insight into the molecular basis of 3β(beta)-hydroxysteroid dehydrogenase deficiency: identification of eight mutations in the HSD3B2 gene in eleven patients from seven new families and comparison of the functional properties of twenty-five mutant enzymes. J Clin Endocrinol Metab. 1999;84:4410–25.

    CAS  PubMed  Google Scholar 

  34. Marui S, Castro M, Latronico AC, et al. Mutations in the type II 3β(beta)-hydroxysteroid dehydrogenase (HSD3B2) gene can cause premature pubarche in girls. Clin Endocrinol. 2000;52:67–75.

    Article  CAS  Google Scholar 

  35. Grumbach MM, Hughes IA, Conte FA. Disorders of sex differentiation. In: Larsen PR, Kronenberg HM, Melmed S, Polonsky KS, editors. Williams textbook of endocrinology. 10th ed. Philadelphia: Saunders; 2003. p. 842–1002.

    Google Scholar 

  36. Kater CE, Biglieri EG. Disorders of steroid 17 alpha-hydroxylase deficiency. Endocrinol Metab Clin N Am. 1994;23(2):341–57.

    CAS  Google Scholar 

  37. Wolthers OD, Rumsby G, Techatraisak K, et al. 17-Hydroxylase/17,20 lyase deficiency diagnosed during childhood. Horm Res. 2002;57(3–4):133–6.

    CAS  PubMed  Google Scholar 

  38. Marsh CA, Auchus RJ. Fertility in patients with genetic deficiencies of cytochrome P450c17 (CYP17A1): combined 17-hydroxylase/17,20-lyase deficiency and isolated 17,200lyase deficiency. Fertil Steril. 2014;101(2):317–22.

    Article  CAS  PubMed  Google Scholar 

  39. Yanase T, Simpson ER, Waterman MR. 17Alpha-hydroxylase/17,20-lyase deficiency: from clinical investigation to molecular definition. Endocr Rev. 1991;12:91–108.

    Article  CAS  PubMed  Google Scholar 

  40. Zachmann M. Prismatic cases: 17,10-desmolase (17,20-lyase) deficiency. Clin Endocrinol. 1996;81:457–9.

    CAS  Google Scholar 

  41. Geller DH, Auchus RJ, Mendonca BB, et al. The genetic and functional basis of isolated 17,20-lyase deficiency. Nat Genet. 1997;17:201–5.

    Article  CAS  PubMed  Google Scholar 

  42. Turan S, Bereket A, Guran T, et al. Puberty in a case with novel 17-hydroxylase mutation and the putative role of estrogen in development of pubic hair. Eur J Endocrinol. 2009;160(2):325–30. [Epub 2008 Nov 7].

    Article  CAS  PubMed  Google Scholar 

  43. Müssig K, Kaltenbach S, Machicao F, et al. 17Alpha-hydroxylase/17,20-lyase deficiency caused by a novel homozygous mutation (Y27Stop) in the cytochrome CYP17 gene. J Clin Endocrinol Metab. 2005;90(7):4362–5.

    Article  PubMed  CAS  Google Scholar 

  44. Patocs A, Liko I, Varga I, et al. Novel mutation of the CYP17 gene in two unrelated patients with combined 17alpha-hydroxylase/17,20-lyase deficiency: demonstration of absent enzyme activity by expressing the mutant CYP17 gene and by three-dimensional modeling. J Steroid Biochem Mol Biol. 2005;97(3):257–65. [Epub 2005 Sep 19].

    Article  CAS  PubMed  Google Scholar 

  45. Turkkahraman D, Guran T, Ivison H, Griffin A, Vijzelaar R, Krone N. Identification of a novel large CYP17A1 deletion by MLPA analysis in a family with classic 17α-hydroxylase deficiency. Sex Dev. 2015;9(2):91–7.

    Article  CAS  PubMed  Google Scholar 

  46. Kim YM, Kang M, Choi JH, Lee BH, Kim GH, Ohn JH, Kim SY, Park MS, Yoo HW. A review of the literature on common CYP17A1 mutations in adults with 17-hydroxylase/17,20-lyase deficiency, a case series of such mutations among Koreans and functional characteristics of a novel mutation. Metabolism. 2014;63(1):42–9. Epub 2013 Oct 18.

    Article  CAS  PubMed  Google Scholar 

  47. Trakakis E, Basios G, Trompoukis P, Labos G, Grammatikakis I, Kassanos D. An update to 21-hydroxylase deficient congenital adrenal hyperplasia. Gynecol Endocrinol. 2010;26(1):63–71.

    Article  CAS  PubMed  Google Scholar 

  48. Speiser PW, Dupont B, Rubinstein P, et al. High frequency of nonclassical steroid 21-hydroxylase deficiency. Am J Hum Genet. 1985;37:650–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Armengaud JB, Charkaluk ML, Trivin C, et al. Precocious pubarche: distinguishing late-onset congenital adrenal hyperplasia from premature adrenarche. J Clin Endocrinol Metab. 2009;94:2835–40.

    Article  CAS  PubMed  Google Scholar 

  50. Witchel SF, Azziz R. Congenital adrenal hyperplasia. J Pediatr Adolesc Gynecol. 2011;24(3):116–26.

    Article  PubMed  Google Scholar 

  51. Choi JH, Kim GH, Yoo HW. Recent advances in biochemical and molecular analysis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Ann Pediatr Endocrinol Metab. 2016;21(1):1–6.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Concolino P, Mello E, Toscano V, Ameglio F, Zuppi C, Capoluongo E. Multiplex ligation-dependent probe amplification (MLPA) assay for the detection of CYP21A2 gene deletions/duplications in congenital adrenal hyperplasia: first technical report. Clin Chim Acta. 2009;402:164–70.

    Article  CAS  PubMed  Google Scholar 

  53. Reisch N, Hogler W, Parajes S, Rose IT, Dhir V, Gotzinger J, Arlt W, Krone N. A diagnosis not to be missed: nonclassic steroid 11β-hydroxylase deficiency presenting with premature adrenarche and hirsutism. J Clin Endocrinol Metab. 2013;98(10):E1620–5.

    Article  CAS  PubMed  Google Scholar 

  54. Krone N, Arlt W. Genetics of congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab. 2009;23(2):181–92.

    Article  CAS  PubMed  Google Scholar 

  55. Chabraoui L, Abid F, Menassa R, et al. Three novel CYP11B1 mutations in congenital adrenal hyperplasia due to steroid 11beta-hydroxylase deficiency in a Moroccan population. Horm Res Paediatr. 2010;74:182–9.

    Article  CAS  PubMed  Google Scholar 

  56. Krone N, Grischuk Y, Müller M, et al. Analyzing the functional and structural consequences of two point mutations (P48L and A368D) in the CYP11B1 gene causing congenital adrenal hyperplasia resulting from 11-hydroxylase deficiency. J Clin Endocrinol Metab. 2006;91(7):2682–8.

    Article  CAS  PubMed  Google Scholar 

  57. Parajes S, Loidi L, Reisch N, et al. Functional consequences of seven novel mutations in the CYP11B1 gene: four mutations associated with nonclassic and three mutations causing classic 11β(beta)-hydroxylase deficiency. J Clin Endocrinol Metab. 2010;95(2):779–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Krone N, Grötzinger J, Holterhus PM, et al. Congenital adrenal hyperplasia due to 11-hydroxylase deficiency-insights from two novel CYP11B1 mutations (p.M92X, p.R453Q). Horm Res. 2009;72:281–6.

    Article  CAS  PubMed  Google Scholar 

  59. Zheng-qin Y, Man-na Z, Hui-jie Z, et al. A novel missense mutation, GGC(Arg454) → TGC(Cys), of CYP11B1 gene identified in a Chinese family with steroid 11β(beta)-hydroxylase deficiency. Chin Med J. 2010;123(10):1264–8.

    Google Scholar 

  60. Kandemir N, Yilmaz DY, Gonc EN, Ozon A, Alikasifoglu A, Dursun A, Ozgul RK. Novel and prevalent CYP11B1 gene mutations in Turkish patients with 11-β hydroxylase deficiency. J Steroid Biochem Mol Biol. 2017;165:57–63.

    Article  CAS  PubMed  Google Scholar 

  61. Wang X, Nie M, Lu L, Tong A, Chen S, Lu Z. Identification of several novel CYP11B1 gene mutations in Chinese patients with 11β hydroxylase deficiency. Steroids. 2015;100:11–6.

    Article  CAS  PubMed  Google Scholar 

  62. Dumic K, Yuen T, Grubic Z, Kusec V, Barisic I, New MI. Two novel CYP11B1 gene mutations in patients from two Croatian families with 11β hydroxylase deficiency. Int J Endocrinol. 2014;2014:185974. Epub 2014 Jun 2.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Polat S, Kulle A, Karaca Z, Akkurt I, Kurtoglu S, Kelestimur F, Grotzinger J, Holterhus PM, Riepe FG. Characterisation of three novel CYP11B1 mutations in classic and non-classic 11β-hydroxylase deficiency. Eur J Endocrinol. 2014;170(5):697–706. Print 2014 May.

    Article  CAS  PubMed  Google Scholar 

  64. Geley S, Kapelari K, Jöhrer K, et al. CYP11B1 mutations causing congenital adrenal hyperplasia due to 11β(beta)-hydroxylase deficiency. J Clin Endocrinol Metab. 1996;81:2896–901.

    CAS  PubMed  Google Scholar 

  65. White PC, Curnow KC, Pascoe L. Disorders of steroid 11β(beta)-hydroxylase isozymes. Endocr Rev. 1994;15:421–38.

    CAS  PubMed  Google Scholar 

  66. Merke DP, Tajima T, Chhabra A, et al. Novel CYP11B1 mutations in congenital adrenal hyperplasia due to steroid 11β(beta)-hydroxylase deficiency. J Clin Endocrinol Metab. 1998;83:270–3.

    CAS  PubMed  Google Scholar 

  67. Zachmann M, Tassinari D, Prader A. Clinical and biochemical variability of congenital adrenal hyperplasia due to 11β(beta)-hydroxylase deficiency: a study of 25 patients. J Clin Endocrinol Metab. 1983;56:222–9.

    Article  CAS  PubMed  Google Scholar 

  68. Peterson RE, Imperato-McGinley J, Gautier T, Shackleton C. Male pseudohermaphroditism due to multiple defects in steroid-biosynthetic microsomal mixed-function oxidases: a new variant of congenital adrenal hyperplasia. N Engl J Med. 1985;313:1182–91.

    Article  CAS  PubMed  Google Scholar 

  69. Flück CE, Tajima T, Pandey AV, et al. Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Nat Genet. 2004;36:228–30.

    Article  PubMed  CAS  Google Scholar 

  70. Arlt W, Walker EA, Draper N, et al. Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study. Lancet. 2004;363:2128–35.

    Article  CAS  PubMed  Google Scholar 

  71. Adachi M, Tachibana K, Asakura Y, et al. Compound heterozygous mutations of cytochrome P450 oxidoreductase gene (POR) in two patients with Antley-Bixler syndrome. Am J Med Genet A. 2004;128:333–9.

    Article  Google Scholar 

  72. Miller WL. P450 oxidoreductase deficiency: a new disorder of steroidogenesis with multiple clinical manifestations. Trends Endocrinol Metab. 2004;15:311–5.

    Article  CAS  PubMed  Google Scholar 

  73. Burkhard FZ, Parween S, Udhane SS, Fluck CE, Pandey AV. P450 Oxidoreductase deficiency: analysis of mutations and polymorphisms. J Steroid Biochem Mol Biol. 2017;165:38–50.

    Article  CAS  PubMed  Google Scholar 

  74. Miller WL, Huang N, Agrawal V, Giacomini KM. Genetic variation in human P450 oxidoreductase. Mol Cell Endocrinol. 2009;300(1–2):180–4. [Epub 2008 Sep 26, Review].

    Article  CAS  PubMed  Google Scholar 

  75. Fukami M, Nishimura G, Homma K, et al. Cytochrome P450 oxidoreductase deficiency: identification and characterization of biallelic mutations and genotype-phenotype correlations in 35 Japanese patients. J Clin Endocrinol Metab. 2009;94(5):1723–31.

    Article  CAS  PubMed  Google Scholar 

  76. Antley R, Bixler D. Trapezoidocephaly, midfacial hypoplasia and cartilage abnormalities with multiple synostoses and skeletal fractures. Birth Defects Orig Artic Ser. 1975;11:397–401.

    CAS  PubMed  Google Scholar 

  77. Reardon W, Smith A, Honour JW, Hindmarsh P, Das D, Rumsby G, Nelson I, Malcolm S, Ades L, Sillence D, Kumar D, DeLoizier-Blanchet C, McKee S, Kelly T, McKeehan WL, Baraitser M, Winter RM. Evidence for digenic inheritance in some cases of Antley-Bixler syndrome? J Med Genet. 2000;37:26–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Crisponi G, Porcu C, Piu ME. Antley-Bixler syndrome: case report and review of the literature. Clin Dysmorphol. 1997;6:61–8.

    Article  CAS  PubMed  Google Scholar 

  79. Huang N, Pandey AV, Agrawal V, et al. Diversity and function of mutations in P450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis. Am J Hum Genet. 2005;76:729–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Miller WL, Agrawal V, Sandee D, Tee MK, Huang N, Choi JH, Morrissey K, Giocomini KM. Consequences of POR mutations and polymorphisms. Mol Cell Endocrinol. 2011;336(1–2):174–9.

    Article  CAS  PubMed  Google Scholar 

  81. Flück CE, Pandey AV, Huang N, et al. P450 oxidoreductase deficiency—a new form of congenital adrenal hyperplasia. Endocr Dev. 2008;13:67–81.

    Article  PubMed  Google Scholar 

  82. Sahakitrungruang T, Huang N, Tee MK, et al. Clinical, genetic, and enzymatic characterization of P450 oxidoreductase deficiency in four patients. J Clin Endocrinol Metab. 2009;94(12):4992–5000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Speiser PW, Azziz R, Baskin LS, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(9):4133–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Webb EA, Krone N. Current and novel approaches to children and young people with adrenal hyperplasia and adrenal insufficiency. Best Pract Res Clin Endocrinol Metab. 2015;29(3):449–68.

    Article  PubMed  Google Scholar 

  85. Johannsson G, Skrtic S, Lennernas H, Quinkler M, Stewart PM. Improving outcomes in patients with adrenal insufficiency: a review of current and future treatments. Curr Med Res Opin. 2014;30(9):1833–47.

    Article  CAS  PubMed  Google Scholar 

  86. Merke DP, Poppas DP. Management of adolescents with congenital adrenal hyperplasia. Lancet Diabetes Endocrinol. 2013;1(4):341–52.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Rivkees SA, Crawford JD. Dexamethasone treatment of virilizing congenital adrenal hyperplasia: the ability to achieve normal growth. Pediatrics. 2000;106:767–73.

    Article  CAS  PubMed  Google Scholar 

  88. Punthakee Z, Legault L, Polychronakos C. Prednisolone in the treatment of adrenal insufficiency: a re-evaluation of relative potency. J Pediatr. 2003;143:402–5.

    Article  CAS  PubMed  Google Scholar 

  89. Bonfig W, Schwarz HP. Blood pressure, fludrocortisone dose and plasma renin activity in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency followed from birth to 4 years of age. Clin Endocrinol. 2014;81(6):871–5.

    Article  CAS  Google Scholar 

  90. Schober JM. Feminizing genitoplasty for intersex. In: Stringer MD, Oldham KT, Moriquand PDE, Howard BR, editors. Pediatric surgery and urology: long term outcomes. Philadelphia: Saunders; 1998. p. 549–58.

    Google Scholar 

  91. Meyer-Bahlburg HFL. What causes low rates of child-bearing in congenital adrenal hyperplasia? J Clin Endocrinol Metab. 1999;84:1844–7.

    Article  CAS  PubMed  Google Scholar 

  92. Alizai NK, Thomas DFM, Lilford TRJ, et al. Feminizing genitoplasty for congenital adrenal hyperplasia: what happens at puberty? J Urol. 1999;161:1588–91.

    Article  CAS  PubMed  Google Scholar 

  93. Krege S, Walz KH, Hauffa BP, et al. Long-term follow-up of female patients with congenital adrenal hyperplasia from 21-hydroxylase deficiency, with special emphasis on the results of vaginoplasty. BJU Int. 2000;86:253–9.

    Article  CAS  PubMed  Google Scholar 

  94. Mouriguand PD, Gorduza DB, Gay CL, Meyer-Bahlburg HF, Baker L, Baskin LS, Bouvattier C, Braga LH, Caldamone AC, Duranteau L, El Ghoneimi A, Hensle TW, Hoebeke P, Kaefer M, Kalfa N, Kolon TF, Manzoni G, Mure PY, Nordenskjold A, Pippi Salle JL, Poppas DP, Ransley PG, Rink RC, Rodrigo R, Sann L, Schober J, Sibai H, Wisniewski A, Wolffenbuttel KP, Lee P. Surgery in disorders of sex development (DSD) with a gender issue: if (why), when, and how? J Pediatr Urol. 2016;12(3):139–49.

    Article  Google Scholar 

  95. Soliman AT, AlLamki M, AlSalmi I, et al. Congenital adrenal hyperplasia complicated by central precocious puberty: linear growth during infancy and treatment with gonadotropin-releasing hormone analog. Metabolism. 1997;46:513–7.

    Article  CAS  PubMed  Google Scholar 

  96. Guven A, Nurcan Cebeci A, Hancili S. Gonadotropin releasing hormone analog treatment in children with congenital adrenal hyperplasia complicated by precocious puberty. Hormones (Athens). 2015;14(2):265–71.

    Google Scholar 

  97. Laue L, Merke DP, Jones JV, et al. A preliminary study of flutamide, testolactone, and reduced hydrocortisone dose in the treatment of congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1996;81:3535–9.

    CAS  PubMed  Google Scholar 

  98. Merke DP, Keil MF, Jones JV, et al. 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.

    Article  CAS  PubMed  Google Scholar 

  99. Juan L, Huamei M, Zhe S, Yanhong L, Hongshan C, Qiuli C, Jun Z, Song G, Minlian D. Near-final health in 82 Chinese patients with congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency: a single-center study from China. J Pediatr Endocrinol Metab. 2016;29(7):841–8.

    Article  PubMed  CAS  Google Scholar 

  100. Alvi S, Shaw NJ, Rayner PHW, et al. Growth hormone and goserelin in congenital adrenal hyperplasia. Horm Res. 1997;48(Suppl 2):1–201.

    Google Scholar 

  101. Quintos JB, Vogiatzi MG, Harbison MD, et al. Growth hormone and depot leuprolide therapy for short stature in children with congenital adrenal hyperplasia. Annual Meeting Endocrine Society; 1999. [Program and Abstracts: 110].

    Google Scholar 

  102. Longui CA, Kochi C, Calliari LE, Modkovski MB, Soares M, Alves EF, Prudente FV, Monte O. Near-final height in patients with congenital adrenal hyperplasia treated with combined therapy using GH and GnRHa. Arg Bras Endocrinol Metab. 2011;55(8):661–4.

    Article  Google Scholar 

  103. Lin-Su K, Harbison MD, Lekarev O, Vogiatzi MG, New MI. Final adult height in children with congenital adrenal hyperplasia treated with growth hormone. J Clin Endocrinol Metab. 2011;96(6):1710–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. 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.

    CAS  PubMed  Google Scholar 

  105. Gallagher MP, Levine LS, Oberfield SE. A review of the effects of therapy on growth and bone mineralization in children with congenital adrenal hyperplasia. Growth Hormon IGF Res. 2005;15(Suppl A):26–30.

    Article  CAS  Google Scholar 

  106. Van Wyk JJ, Gunther DF, Ritzen EM, et al. Therapeutic controversies: the use of adrenalectomy as a treatment for congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1996;81:3180–90.

    PubMed  Google Scholar 

  107. Gunther DF, Bukowski TP, Titzen EM, et al. Prophylactic adrenalectomy of a three-year-old girl with congenital adrenal hyperplasia: pre- and postoperative studies. J Clin Endocrinol Metab. 1997;82:3324–7.

    CAS  PubMed  Google Scholar 

  108. Nasir J, Royston C, Walton C, et al. 11β(beta)-hydroxylase deficiency: management of a difficult case by laparoscopic bilateral adrenalectomy. Clin Endocrinol. 1996;45:225–8.

    Article  CAS  Google Scholar 

  109. Chabre O, Portrat-Doyen S, Chaffanjon P, et al. Bilateral laparoscopic adrenalectomy for congenital adrenal hyperplasia with severe hypertension, resulting from two novel mutations in splice donor sites of CYP11B1. J Clin Endocrinol Metab. 2000;85:4060–8.

    Article  CAS  PubMed  Google Scholar 

  110. Wudy SA, Choi MH. Steroid LC-MS has come of age. J Steroid Biochem Mol Biol. 2016;162:1–3.

    Article  CAS  PubMed  Google Scholar 

  111. Lo JC, Schwitzgebel VM, Tyrrell JB, et al. Normal female infants born of mothers with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab. 1999;84:930–6.

    CAS  PubMed  Google Scholar 

  112. Lim YJ, Batch JA, Warne GL. Adrenal 21-hydroxylase deficiency in childhood: 25 years’ experience. J Paediatr Child Health. 1995;31:222–7.

    Article  CAS  PubMed  Google Scholar 

  113. Rasat R, Espiner EA, Abbott GD. Growth patterns and outcomes in congenital adrenal hyperplasia: effects of chronic treatment regimens. N Z Med J. 1995;108:311–4.

    CAS  PubMed  Google Scholar 

  114. 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.

    Article  CAS  PubMed  Google Scholar 

  115. Hauffa BP, Winter A, Stolecke H. Treatment and disease effects on short-term growth and adult height in children and adolescents with 21-hydroxylase deficiency. Klin Padiatr. 1997;209:71–7.

    Article  CAS  PubMed  Google Scholar 

  116. 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.

    Article  CAS  PubMed  Google Scholar 

  117. Kandemir N, Yordam N. Congenital adrenal hyperplasia in Turkey: a review of 273 patients. Acta Paediatr. 1997;86:22–5.

    Article  CAS  PubMed  Google Scholar 

  118. Kuhnle U, Bullinger M. Outcome of congenital adrenal hyperplasia. Pediatr Surg Int. 1997;12:511–5.

    Article  CAS  PubMed  Google Scholar 

  119. Premawardhana LDKE, Hughes IA, Read GH, et al. Longer term outcome in females with congenital adrenal hyperplasia (CAH): the Cardiff experience. Clin Endocrinol. 1997;46:327–32.

    Article  CAS  Google Scholar 

  120. 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.

    Article  CAS  PubMed  Google Scholar 

  121. Schwartz RP. Back to basics: early diagnosis and compliance improve final height outcome in congenital adrenal hyperplasia. J Pediatr. 2001;138:3–5.

    Article  CAS  PubMed  Google Scholar 

  122. Diamond M. Prenatal predisposition and the clinical management of some pediatric conditions. J Sex Marital Ther. 1996;22:139.

    Article  CAS  PubMed  Google Scholar 

  123. Diamond M, Sigmundson HK. Sex reassignment at birth. Arch Pediatr Adolesc. 1997;151:298.

    Article  CAS  Google Scholar 

  124. Silveira MT, Knobloch F, Silva Janovsky CC, Kater CE. Gender dysphoria in a 62-year-old genetic female with congenital adrenal hyperplasia. Arch Sex Behav. 2016;45(7):1871–5.

    Article  PubMed  Google Scholar 

  125. Furtado PS, Moraes F, Lago R, Barros LO, Toralles MB, Barroso U Jr. Gender dysphoria associated with disorders of sex development. Nat Rev Urol. 2012;9(11):620–7.

    Article  CAS  PubMed  Google Scholar 

  126. Hagenfeldt K, Ritzen EM, Ringertz H, et al. Bone mass and body composition of adult women with congenital virilizing 21-hydroxylase deficiency after glucocorticoid treatment since infancy. Eur J Endocrinol. 2000;143:667–71.

    Article  CAS  PubMed  Google Scholar 

  127. Schulz J, Frey KR, Cooper MS, Zopf K, Ventz M, Diederich S, Quinkler M. Reduction in daily hydrocortisone dose improves bone health in primary adrenal insufficiency. Eur J Endocrinol. 2016;174(4):531–8.

    Article  CAS  PubMed  Google Scholar 

  128. Nimkarn S, New MI. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a paradigm for prenatal diagnosis and treatment. Ann N Y Acad Sci. 2010;1192:5–11.

    Article  CAS  PubMed  Google Scholar 

  129. New MI, Abraham M, Yuen T, Lekarev O. An update on prenatal diagnosis and treatment of congenital adrenal hyperplasia. Semin Reprod Med. 2012;30(5):396–9.

    Article  PubMed  Google Scholar 

  130. Tardy-Guidollet V, Menassa R, Costa JM, David M, Bouvattier-Morel C, Baumann C, Houang M, Lorenzini F, Philip N, Odent S, Guichet A, Morel Y. New management strategy of pregnancies at risk of congenital adrenal hyperplasia using fetal sex determination in maternal serum: French cohort of 258 cases (2002–2011). J Clin Endocrinol Metab. 2014;99(4):1180–8.

    Article  CAS  PubMed  Google Scholar 

  131. Lo YM, Tein MS, Lau TK, Haines CJ, Leung TN, Poon PM, Wainscoat JS, Johnson PJ, Chang AM, Hjelm NM. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet. 1998;62(4):768–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Chiu RW, Lau TK, Cheung PT, Gong ZQ, Leung TN, Lo YM. Noninvasive prenatal exclusion of congenital adrenal hyperplasia by maternal plasma analysis: a feasible study. Clin Chem. 2002;48(5):778–80.

    CAS  PubMed  Google Scholar 

  133. New MI, Tong YK, Yuen T, Jiang P, Pina C, Chan KC, Khattab A, Liao GJ, Yau M, Kim SM, Chiu RW, Sun L, Zaidi M, Lo YM. Noninvasive prenatal diagnosis of congenital adrenal hyperplasia using cell-free fetal DNA in maternal plasma. J Clin Endocrinol Metab. 2014;99(6):E1022–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Yau M, Khattab A, New MI. Prenatal diagnosis of congenital adrenal hyperplasia. Endocrinol Metab Clin N Am. 2016;45(2):267–81.

    Article  Google Scholar 

  135. Forest MG, Morel Y, David M. Prenatal treatment of congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. Front Endocrinol. 1996;17:77–89.

    Google Scholar 

  136. Carlson AD, Obeid JS, Kanellopoulou N, et al. Congenital adrenal hyperplasia: update on prenatal diagnosis and treatment. J Steroid Biochem Mol Biol. 1999;69:19–29.

    Article  CAS  PubMed  Google Scholar 

  137. Rosler A, Weshler N, Leiberman E, et al. 11β(Beta)-hydroxylase deficiency congenital adrenal hyperplasia: update of prenatal diagnosis. J Clin Endocrinol Metab. 1988;66:830–8.

    Article  CAS  PubMed  Google Scholar 

  138. Cerame BI, Newfield RS, Pascoe L, et al. Prenatal diagnosis and treatment of 11β(beta)-hydroxylase deficiency congenital adrenal hyperplasia resulting in normal female genitalia. J Clin Endocrinol Metab. 1999;84:3129–34.

    CAS  PubMed  Google Scholar 

  139. Izumi H, Saito N, Ichiki S, et al. Prenatal diagnosis of congenital lipoid adrenal hyperplasia. Obstet Gynecol. 1993;81:839–41.

    CAS  PubMed  Google Scholar 

  140. Saenger P. New developments in congenital lipoid adrenal hyperplasia and steroidogenic acute regulatory protein. Pediatr Clin N Am. 1997;44:397–421.

    Article  CAS  Google Scholar 

  141. David M, Forest MG. Prenatal treatment of congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency. J Pediatr. 1984;105:799–803.

    Article  CAS  PubMed  Google Scholar 

  142. White PC, Mune T, Agarwal AK. 11β(beta)-hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. Endocr Rev. 1997;18:135–56.

    CAS  PubMed  Google Scholar 

  143. 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.

    Article  CAS  PubMed  Google Scholar 

  144. Levine LS, Pang S. Prenatal diagnosis and treatment of congenital adrenal hyperplasia. In: Milunsky A, editor. Genetic disorders and the fetus: diagnosis, prevention and treatment. 4th ed. Baltimore: The Johns Hopkins University Press; 1998. p. 529–49.

    Google Scholar 

  145. 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.

    CAS  PubMed  Google Scholar 

  146. Forest MG, Dorr HG. Prenatal treatment of congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency: European experience in 253 pregnancies at risk. Clin Cour. 1993;11:2–3.

    Google Scholar 

  147. Lajic S, Wedell A, Bui T, et al. Long-term somatic follow-up of prenatally treated children with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1998;83:3872–80.

    CAS  PubMed  Google Scholar 

  148. Trautman PD, Meyer-Bahlburg HFL, Postelnek J, et al. Effects of early prenatal dexamethasone on the cognitive and behavioral development of young children: results of a pilot study. Psychoneuroendocrinology. 1995;20:439–49.

    Article  CAS  PubMed  Google Scholar 

  149. Meyer-Bahlburg HF, Dolezal C, Baker SW, et al. Cognitive and motor development of children with and without congenital adrenal hyperplasia after early-prenatal dexamethasone. J Clin Endocrinol Metab. 2004;89:610–4.

    Article  CAS  PubMed  Google Scholar 

  150. Hirvikoski T, Nordenström A, Lindholm T, et al. Long-term follow-up of prenatally treated children at risk for congenital adrenal hyperplasia: does dexamethasone cause behavioral problems? Eur J Endocrinol. 2008;159:309–16.

    Article  CAS  PubMed  Google Scholar 

  151. Hirvikoski T, Nordenström A, Lindholm T, et al. Cognitive functions in children at risk for congenital adrenal hyperplasia treated prenatally with dexamethasone. J Clin Endocrinol Metab. 2007;92:542–8.

    Article  CAS  PubMed  Google Scholar 

  152. Wallensteen L, Zimmermann M, Thomsen Sandberg M, Gezelius A, Nordenstrom A, Hirvikoski T, Lajic S. Sex-dimorphic effects of prenatal treatment with dexamethasone. J Clin Endocrinol Metab. 2016;101(10):3838–46.

    Article  CAS  PubMed  Google Scholar 

  153. Meyer-Bahlburg HF, Dolezal C, Haggerty R, Silverman M, New MI. Cognitive outcome of offspring from dexamethasone-treated pregnancies at risk for congenital adrenal hyperplasia due to 21-hydroxylate deficiency. Eur J Endocrinol. 2012;167(1):103–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Forest MG, Morel Y, David M. Prenatal treatment of congenital adrenal hyperplasia. Trends Endocrinol Metab. 1998;9:284–8.

    Article  CAS  PubMed  Google Scholar 

  155. Trautman PD, Meyer-Bahlburg HF, Postelnek J, et al. Mothers’ reactions to prenatal diagnostic procedures and dexamethasone treatment of congenital adrenal hyperplasia. J Psychosom Obstet Gynaecol. 1996;17:175–81.

    Article  CAS  PubMed  Google Scholar 

  156. Hirvikoski T, Nordenstrom A, Wedell A, Ritzen M, Lajic S. Prenatal dexamethasone treatment of children at risk for congenital adrenal hyperplasia: the Swedish experience and standpoint. J Clin Endocrinol Metab. 2012;97(6):1881–3.

    Article  CAS  PubMed  Google Scholar 

  157. Miller WL, Witchel SF. Prenatal treatment of congenital adrenal hyperplasia: risks outweigh benefits. Am J Obstet Gynecol. 2013;208(5):354–9.

    Article  PubMed  Google Scholar 

  158. Miller WL. Fetal endocrine therapy for congenital adrenal hyperplasia should not be done. Best Pract Res Clin Endocrinol Metab. 2015;29(3):469–83.

    Article  PubMed  Google Scholar 

  159. Miller WL. Prenatal treatment of congenital adrenal hyperplasia: a promising experimental therapy of unproven safety. Trends Endocrinol Metab. 1998;9:290–3.

    Article  CAS  PubMed  Google Scholar 

  160. Pang S, Hotchkiss J, Drash AL, et al. Microfilter paper method for 17α(alpha)-hydroxyprogesterone radioimmunoassay; its application for rapid screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1977;45:1003–8.

    Article  CAS  PubMed  Google Scholar 

  161. Pang S, Murphey W, Levine LS, et al. A pilot newborn screening for congenital adrenal hyperplasia in Alaska. J Clin Endocrinol Metab. 1982;55:413–20.

    Article  CAS  PubMed  Google Scholar 

  162. Pang S, Wallace MA, Hofman L, et al. Worldwide experience in newborn screening for classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Pediatrics. 1988;81:866–74.

    CAS  PubMed  Google Scholar 

  163. Pang S, Clark A. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: newborn screening and its relationship to the diagnosis and treatment of the disorder. Screening. 1993;2:105–39.

    Article  Google Scholar 

  164. 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. Pediatrics. 1996;98:362–7.

    CAS  PubMed  Google Scholar 

  165. Cutfield WS, Webster D. Newborn screening for congenital adrenal hyperplasia in New Zealand. J Pediatr. 1995;126:118–21.

    Article  CAS  PubMed  Google Scholar 

  166. Dotti G, Pagliardini S, Vuolo A, et al. Congenital adrenal hyperplasia in the experience of the Piemonte and Valle d’Aosta regions program (1987–1995). In: Programs & abstracts of the 3rd international newborn screening meeting, Boston, 22–23 Oct 1996 [Abstract No. P-82].

    Google Scholar 

  167. Nordenström A, Thilén A, Hagenfeldt L, et al. Benefits of screening for congenital adrenal hyperplasia (CAH) in Sweden. In: Levy HL, Hermos RJ, Grady GF, editors. Proceedings, third meeting of the international society for neonatal screening, Boston, 22–23 Oct 1996. p. 211–216.

    Google Scholar 

  168. Sack J, Front H, Kaiserman I, et al. Screening for 21-hydroxylase deficiency in Israel. In: Programs & abstracts of the 3rd international newborn screening meeting, Boston, 22–23 Oct 1996 [Abstract No. P-87].

    Google Scholar 

  169. Al-Nuaim AA. Newborn screening program (NSP) in Saudi Arabia (SA). In: Programs & abstracts of the 3rd international newborn screening meeting, Boston 22–23 Oct 1996 [Abstract No. P-90].

    Google Scholar 

  170. Pang S, Shook M. Current status of newborn screening for congenital adrenal hyperplasia. Curr Opin Pediatr. 1997;9:419–23.

    Article  CAS  PubMed  Google Scholar 

  171. 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.

    Article  CAS  PubMed  Google Scholar 

  172. Herrel 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.

    Article  Google Scholar 

  173. Allen DB, Hoffman GL, Mahy SL, et al. Improved precision of newborn screening for congenital adrenal hyperplasia using weight adjusted criteria for 17-hydroxyprogesterone levels. J Pediatr. 1997;130:120–33.

    Article  Google Scholar 

  174. Brosnan PG, Brosnan CA, Kemp SF, et al. Effect of newborn screening for congenital adrenal hyperplasia. Arch Pediatr Adolesc Med. 1999;153:1272–8.

    Article  CAS  PubMed  Google Scholar 

  175. Kwon C, Farrell PM. The magnitude and challenge of false-positive newborn screening test results. Arch Pediatr Adolesc Med. 2000;154:714–8.

    Article  CAS  PubMed  Google Scholar 

  176. Matern D, Tortorelli S, Oglesbee D, et al. Reduction of the false-positive rate in newborn screening by implementation of MS/MS-based second-tier tests: the Mayo Clinic experience (2004–2007). J Inherit Metab Dis. 2007;30:585–92.

    Article  CAS  PubMed  Google Scholar 

  177. Lacey JM, Minutti CZ, Magera MJ, et al. Improved specificity of newborn screening for congenital adrenal hyperplasia by second-tier steroid profiling using tandem mass spectrometry. Clin Chem. 2004;50:621–5.

    Article  CAS  PubMed  Google Scholar 

  178. Rauh M, Gröschl M, Rascher W, Dorr HG. Automated, fast and sensitive quantification of 17α(alpha)-hydroxy-progesterone, androstenedione and testosterone by tandem mass spectrometry with on-line extraction. Steroids. 2006;71:450–8.

    Article  CAS  PubMed  Google Scholar 

  179. Janzen N, Sander S, Terhardt M, et al. Fast and direct quantification of adrenal steroids by tandem mass spectrometry in serum and dried blood spots. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;861:117–22.

    Article  CAS  PubMed  Google Scholar 

  180. Boelen A, Ruiter AF, Classhsen-van der Grinten HL, Endert E, Ackermans MT. Determination of a steroid profile in heel prick blood using LC-MS/MS. Bioanalysis. 2016;8(5):375–84.

    Article  CAS  PubMed  Google Scholar 

  181. Tajima T, Fukushi M. Neonatal mass screening for 21-hydroxylase deficiency. Clin Pediatr Endocrinol. 2016;25(1):1–8.

    Article  PubMed  PubMed Central  Google Scholar 

  182. Monostori P, Szabo P, Marginean O, Bereczki C, Karg E. Concurrent confirmation and differential diagnosis of congenital adrenal hyperplasia from dried blood spots: application of a second-tier LC-MS/MS assay in a cross-border cooperation for newborn screening. Horm Res Paediatr. 2015;84(5):311–8.

    Article  CAS  PubMed  Google Scholar 

  183. Seo JY, Park HD, Kim JW, Oh HJ, Yang JS, Chang YS, Park WS, Lee SY. Steroid profiling for congenital adrenal hyperplasia by tandem mass spectrometry as a second-tier test reduces follow-up burdens in a tertiary care hospital: a retrospective and prospective evaluation. J Perinat Med. 2014;42(1):121–7.

    Article  CAS  PubMed  Google Scholar 

  184. Miller WL, Levine LS. Molecular and clinical advancements in congenital adrenal hyperplasia. J Pediatr. 1987;111:1.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

We acknowledge Dr. Selma Witchel for her thoughtful review and discussion of this chapter. We also thank Hailey Roumimper, ScB for her editorial assistance with manuscript preparation.

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Authors and Affiliations

  1. Pediatrics, University of Connecticut School of Medicine, Hartford, CT, USA

    Christine M. Trapp MD

  2. Division of Pediatric Diabetes and Endocrinology, Hartford, CT, USA

    Christine M. Trapp MD

  3. Pediatrics, College of Physicians & Surgeons of Columbia University, New York, NY, USA

    Lenore S. Levine MD

  4. Division of Pediatric Endocrinology, Diabetes and Metabolism, Morgan Stanley Children’s Hospital, NY Presbyterian/Columbia University, New York, NY, USA

    Sharon E. Oberfield MD

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  1. Christine M. Trapp MD
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  3. Sharon E. Oberfield MD
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Correspondence to Christine M. Trapp MD .

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Editors and Affiliations

  1. Department of Pediatrics, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

    Sally Radovick

  2. Pediatric Endocrinology, Massachusetts General Hospital for Children, Boston, Massachusetts, USA

    Madhusmita Misra

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Trapp, C.M., Levine, L.S., Oberfield, S.E. (2018). Congenital Adrenal Hyperplasia. In: Radovick, S., Misra, M. (eds) Pediatric Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-73782-9_14

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