Hiperplasia adrenal congénita por déficit de 21 hidroxilasa: un reto diagnóstico y terapéutico
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a therapeutic and diagnosis challenge
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Latorre, S., Garzón, C., Manosalva, G., Merchán, S., Jacomussi, L., & Maldonado, S. (2016). Hiperplasia adrenal congénita por déficit de 21 hidroxilasa: un reto diagnóstico y terapéutico. Revista Repertorio De Medicina Y Cirugía, 25(2), 79–88. Recuperado a partir de https://revistas.fucsalud.edu.co/index.php/repertorio/article/view/81
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Jun 1, 2016
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La hiperplasia adrenal congénita es un conjunto de anomalías con herencia autosómica recesiva por el déficit de una de las cinco enzimas necesarias para la síntesis de cortisol en la corteza adrenal. La causa más frecuente es la deficiencia de 21 hidroxilasa, que explica más del 95% de los casos. La presentación es heterogénea y depende de cuán afectada está la función enzimática y el sexo del paciente. Se clasifica en una variante no clásica y clásica, esta se subclasifica en una forma con pérdidas salinas y virilizante simple. El tratamiento se fundamenta en el uso de glucocorticoides y mineralocorticoides, con un seguimiento estricto para minimizar las reacciones adversas.
Objetivo: Revisión descriptiva sobre el estado del arte de la hiperplasia adrenal congénita.
Materiales y métodos: Revisión no sistemática de la literatura mediante los buscadores Medline, PubMed, LILACS y la herramienta Clinical Key de publicaciones en los últimos diez años. Se usaron las palabas: hiperplasia adrenal congénita, déficit de 21 hidroxilasa y ambigüedad sexual.
Discusión y conclusión: Como es una enfermedad de gran variabilidad en la presentación clínica y las características paraclínicas, es necesario que los profesionales de la salud tengan amplio conocimiento en cuanto a su forma de presentación, diagnóstico y manejo en situaciones especiales (crisis adrenal, dosis de estrés, embarazo), además de realizar seguimiento regular e intervenciones tempranas con el fin de mermar las consecuencias deletéreas, derivadas del tratamiento con corticoides en forma crónica.
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Referencias
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2. New M, Ghizzoni L, Lin-Su K. An update of congenital adrenal hyperplasia. En: Lifshitz F, editor. Pediatric endocronology. New York: Informa Healthcare; 2007. p. 227–45.
3. Charmandari E, Weise M, Bornstein SR, Eisenhofer G, Keil MF, Chrousos GP, et al. Children with classic congenital adrenal hyperplasia have elevated serum leptin concentrations and insulin resistance: potential clinical implications. J Clin Endocrinol Metab. 2002;87:2114–20.
4. Lambert SM, Vilain EJ, Kolon TF. A practical approach to ambiguous genitalia in the newborn period. Urol Clin North Am. 2010;37:195–205.
5. Witchel SF, Azziz R. Congenital adrenal hyperplasia. J Pediatr Adolesc Gynecol. 2011;24:6–26.
6. Mnif MF, Kamoun M, Mnif F, Charfi N, Kallel N, Ben Naceur B, et al. Long-term outcome of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Am J Med Sci. 2012;344:363–73.
7. Falhammar H, Thorén M. Clinical outcomes in the management of congenital adrenal hyperplasia. Endocrine. 2012;41:355–73.
8. Nimkarn S, Lin-Su K, New MI. Steroid 21 hydroxylase deficiency congenital adrenal hyperplasia. Pediatr Clin North Am. 2011;58:1281–300.
9. Sharma R, Seth A. Congenital adrenal hyperplasia: issues in diagnosis and treatment in children. Indian J Pediatr. 2013, http://dx.doi.org/10.1007/s12098-013-1280-8.
10. Speiser PW, White PC. Congenital adrenal hyperplasia. N Engl J Med. 2003;349:776–88.
11. The Endocrine Society. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2010;95:4133–60.
12. Fernández B, Roldán M, Rodríguez A, Ezquieta B. Consejo genético en la hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa. An Pediatr. 2012;76:51–2.
13. Trapp CM, Speiser PW, Oberfield SE. Congenital adrenal hyperplasia: an update in children. Curr Opin Endocrinol Diabetes Obes. 2011;18:166–70.
14. Kim MS, Ryabets-Lienhard A, Geffner ME. Management of congenital adrenal hyperplasia in childhood. Curr Opin Endocrinol Diabetes Obes. 2012;19:483–8.
15. Cordeiro GV, Silva IN, Goulart EMA, Chagas AJ, Kater CE. Final height in congenital adrenal hyperplasia: the dilemma of hypercortisolism versus hyperandrogenism. Arq Bras Endocrinol Metabol. 2013;57:126–31.
16. Weil AP. La diversidad del sistema endocrino. En: Murray R, Bender D, Botham K, Kennelly P, Rodwell V, Weil P, editores. Harper bioquímica ilustrada. México D.F: McGrawHill; 2009. p. 429–32.
17. Alonso M, Ezquieta B. Hiperplasia suprarrenal congénita no clásica o tardía. Rev Esp Endocrinol Pediatr. 2012;3 Suppl 1:65–73.
18. White PC, Bachega TA. Congenital adrenal hyperplasia due to 21 hydroxylase deficiency: from birth to adulthood. Semin Reprod Med. 2012;30:400–9.
19. Labarta JI, de Arriba A, Ferrández Á. Hiperplasia suprarrenal congénita. Protoc diagn ter pediatr. 2011;1:117–28.
20. Chen Chen W, Xu Z, Sullivan A, Finkielstain GP, Van Ryzin C, Merke DP, et al. Junction site analysis of chimeric CYP21A1P/CYP21A2 genes in 21-hydroxylase deficiency. Clin Chem. 2012;58:421–30.
21. Licourt D, Pérez MM. Déficit de 21-hidroxilasa: aspectos actuales. Rev Ciencias Médicas. 2009;13:116–29.
22. New MI, Abraham M, Gonzalez B, Dumic M, Razzaghy-Azar M, Chitayat D, et al. Genotype-phenotype correlation in 1,507 families with congenital adrenal hyperplasia owing to
21-hydroxylase deficiency. Proc Natl Acad Sci U S A. 2013;110:2611–6.
23. Bidet M, Bellanné-Chantelot C, Galand-Portier M-B, Tardy V, Billaud L, Laborde K, 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;94:1570–8.
24. Haider S, Islam B, D’Atri V, Sgobba M, Poojari C, Sun L, et al. Structure-phenotype correlations of human CYP21A2 mutations in congenital adrenal hyperplasia. Proceedings of the National Academy of Sciences of the United States of America. 2013;110:2605–10.
25. Finkielstain GP, Chen W, Mehta SP, Fujimura FK, Hanna RM, Van Ryzin C, et al. Comprehensive genetic analysis of 182 unrelated families with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2011;96:E161–72.
26. Rodríguez-Arnao M, Rodríguez A, Badillo K, Velasco A, Dulín E, Ezquieta B. Déficit de 21-hidroxilasa: aspectos actuales. Rev Endocrinol Nutr. 2006;53:124–36.
27. al-Attia HM. Male pseudohermaphroditism due to 5 alpha-reductase-2 deficiency in an Arab kindred. Postgrad Med J. 1997;73:802–7.
28. Toscano J, Padilla J, Becerra L, Díaz M, Bañuelos O, Rivas F, et al. Hermafroditismo verdadero y secuencias del cromosoma Y. Implicaciones a propósito de dos casos. Rev Med Inst Mex Seguro Soc. 2008;46:539–42.
29. Falen J, Mio F, del Aguila C, Rojas M, Lu R, Meza M, et al. Características clínicas y hormonales del síndrome de insensibilidad a andrógenos. Rev. Perú. Pediatr. 2008;61:16–21.
30. Sepúlveda J, Sanguino L, Jaimes H. Hiperplasia adrenal congénita. Rev. Colomb. Obstet. Ginecol. 2001;28:52.
31. Hughes IA. Management of congenital adrenal hyperplasia. Arch Dis Child. 1988;63:1399–404.
32. Sanfilippo JS. Congenital adrenal hyperplasia pearls you should know–globally. J Pediatr Adolesc Gynecol. 2013;26:295.
33. Soriano L, Velázquez M. Hiperplasia suprarrenal congénita. Unidad de Endocrinología Infantil. Servicio de Pediatría. Fundación Jiménez Díaz. Madrid. Pediatr Integral. 2007;11:601–10.
34. Ghizzoni L, Cappa M, Vottero A, Ubertini G, Carta D, Di Iorgi N, et al. Relationship of CYP21A2 genotype and serum 17-hydroxyprogesterone and cortisol levels in a large cohort of Italian children with premature pubarche. Eur J Endocrinol. 2011;165:307–14.
35. Cánovas B, González-Albarrán O, Garcia R. Hiperplasia suprarrenal congénita. Medicine. 2000;8:1120–5.
36. New MI, Abraham M, Yuen T, Lekarev O. An update on prenatal diagnosis and treatment of congenital adrenal hyperplasia. Semin Reprod Med. 2012;30:396–9.
37. Botelho C, Novato I, Leite I, Nélio J. Neonatal screening for congenital adrenal hyperplasia. Rev. Assoc. Med. Bras. 2012;58:459–64.
38. Hayashi G, Faure C, Brondi MF, Vallejos C, Soares D, Oliveira E, et al. Weight-adjusted neonatal 17OH-progesterone cutoff levels improve the efficiency of newborn screening for congenital adrenal hyperplasia. Arq Bras Endocrinol Metab. 2011;55:632–7.
39. Kösel S, Burggraf S, Fingerhut R, Dörr HG, Roscher AA, Olgermöller B. Rapid second-tier molecular genetic analysis for congenital adrenal hyperplasia attributable to steroid 21-hydroxylase deficiency. Clin Chem. 2005;51:298–304.
40. Nordenström A, Wedell A, Hagenfeldt L, Marcus C, Larsson A. Neonatal screening for congenital adrenal hyperplasia: 17-hydroxyprogesterone levels and CYP21 genotypes in preterm infants. Pediatrics. 2001;108:e68.
41. Van der Kamp HJ, Oudshoorn CG, Elvers BH, van Baarle M, Otten BJ, Wit JM, et al. Cutoff levels of 17-alfa-hydroxyprogesterone in neonatal screening for congenital adrenal hyperplasia should be based on gestational age rather than on birth weight. J Clin Endocrinol Metab. 2005;90:3904–7.
42. Banks K, Pittock S, Sarafoglou K, Kyllo J, Thomas W. Cases of congenital adrenal hyperplasia missed by newborn screening in minnesota. JAMA. 2012;307:2371–4.
43. Sarafoglou K, Banks K, Gaviglio A, Hietala A, McCann M, Thomas W. Comparison of one-tier and two-tier newborn screening metrics for congenital adrenal hyperplasia. Pediatrics. 2012;130:1261–8.
44. Ryckman K, Cook D, Berberich S, Shchelochkov O, Copeland S, Berends S, et al. Replication of clinical associations with 17-hydroxyprogesterone in preterm newborns. J Pediatr Endocrinol Metab. 2012;25:301–5.
45. Cavarzere P, Samara-Boustani D, Flechtner I, Dechaux M, Elie C, Tardy V, et al. Transient hyper-17-hydroxyprogesteronemia: a clinical subgroup of patients diagnosed at neonatal screening for congenital adrenal hyperplasia. Eur J Endocrinol. 2009;161:285–92.
46. Hindmarsh PC. Management of the child with congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab. 2009;23:193–208.
47. 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;97:1881–3.
48. Fernandez-Balsells M, Muthusamy K, Smushkin G, Lampropulos JF, Elamin MB, Elnour N, et al. Prenatal dexamethasone use for the prevention of virilization in pregnancies at risk for classical congenital adrenal hiperplasia because of 21-hydroxylase (CYP21A2) deficiency: a systematic review and meta-analyses. Clin Endocrinol. 2010;73:436–44.
49. Mesogitis S, Daskalakis G, Papapetrou P, Mavroudis K, Papandroulaki F, Papantoniou N, et al. The effect on the fetal pituitary-adrenal axis of dexamethasone administration early in the second trimester of pregnancy. J Matern Fetal Neonatal Med. 2011;24:109–11.
50. New M. Vidication of prenatal diagnosis and treatment of congenital adrenal hyperplasia with low-dose dexametasone. Am J Bioeth. 2010;10:67–8.
51. Bryan SM, Honour JW, Hindmarsh PC. Management of altered hydrocortisone pharmacokinetics in a boy with congenital adrenal hyperplasia using a continuous subcutaneous hydrocortisone infusión. J Clin Endocrinol Metab. 2009;94:3477–80.
52. Moreira RP, Jorge AL, Gomes LG, Kaupert LC, Massud J, Mendonca BB, et al. Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clinics. 2011;66:1361–5.
53. Takasawa K, Ono M, Miyai K, Matsubara Y, Takizawa F, Onishi T, et al. Initial high dose hydrocortisone (HDC) treatment for 21-hydroxylase deficiency (21-OHD) does not affect linear growth during the first three years of life. Endocr J. 2012;59:1001–6.
54. Gomes LG, Madureira G, Mendonca BB, Bachega T. Mineralocorticoid replacement during infancy for salt wasting congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clinics. 2013;68:147–51.
55. Merke DP, Chrousos GP, Eisenhofer G, Weise M, Keil MF, Rogol AD, et al. Adrenomedullary displasia and hypofunction in patients with classic 21–hydroxylase deficiency. N Engl J Med. 2000;343:1362–8.
56. Loechner K, McLaughlin JT, Calikoglu AS. Alternative strategies for the treatment of classical congenital adrenal hyperplasia: pitfalls and promises. Int J Pediatr Endocrinol. 2010. Article ID 670960.
57. Romao R, Pippi J, Wherrett D. Update on the management of disorders of sex development. Pediatr Clin N Am. 2012;59:853–69.
58. Longui CA, Kochi C, Procópio LE, Rosa MB, Soares M, Ferreira E, et al. Near-final height in patients with congenital adrenal hyperplasia treated with combined therapy using GH and GnRHa. Arq Bras Endocrinol Metab. 2011;55:661–4.
59. Muthusamy K, Elamin MB, Smushkin G, Murad MH, Lampropulos JF, Elamin KB, et al. Clinical review: Adult height in patients with congenital adrenal hyperplasia: A systematic review and metaanalysis. J Clin Endocrinol Metab. 2010;95:4161–72.
60. Völkl T, Simm D, Beier C, Dörr H. Obesity among children and adolescents with classic congenital adrenal hyperplasia due to 21–hydroxylase deficiency. Pediatrics. 2006;117:e98–105.
61. Falhammar H, Filipsson H, Wedell A, Brismar K, Thorén M. Bone mineral density, bone markers and fractures in adult males with congenital adrenal hyperplasia. Eur J Endocrinol. 2013;168:331–41.
62. Arlt W, Willis D, Wild SH, Krone N, Doherty EJ, Hahner S, et al. Health status of adults with congenital adrenal hyperplasia: a cohort study of 203 patients. J Clin Endocrinol Metab. 2010;95:5110–21.
63. Megan C, Crouch N, Rumsby G, Creighton SM, Liao LM, Conway GS. Congenital adrenal hyperplasia in adults: a review of medical, surgical and psychological issues. Clin Endocrinol. 2006;64:2–11.
2. New M, Ghizzoni L, Lin-Su K. An update of congenital adrenal hyperplasia. En: Lifshitz F, editor. Pediatric endocronology. New York: Informa Healthcare; 2007. p. 227–45.
3. Charmandari E, Weise M, Bornstein SR, Eisenhofer G, Keil MF, Chrousos GP, et al. Children with classic congenital adrenal hyperplasia have elevated serum leptin concentrations and insulin resistance: potential clinical implications. J Clin Endocrinol Metab. 2002;87:2114–20.
4. Lambert SM, Vilain EJ, Kolon TF. A practical approach to ambiguous genitalia in the newborn period. Urol Clin North Am. 2010;37:195–205.
5. Witchel SF, Azziz R. Congenital adrenal hyperplasia. J Pediatr Adolesc Gynecol. 2011;24:6–26.
6. Mnif MF, Kamoun M, Mnif F, Charfi N, Kallel N, Ben Naceur B, et al. Long-term outcome of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Am J Med Sci. 2012;344:363–73.
7. Falhammar H, Thorén M. Clinical outcomes in the management of congenital adrenal hyperplasia. Endocrine. 2012;41:355–73.
8. Nimkarn S, Lin-Su K, New MI. Steroid 21 hydroxylase deficiency congenital adrenal hyperplasia. Pediatr Clin North Am. 2011;58:1281–300.
9. Sharma R, Seth A. Congenital adrenal hyperplasia: issues in diagnosis and treatment in children. Indian J Pediatr. 2013, http://dx.doi.org/10.1007/s12098-013-1280-8.
10. Speiser PW, White PC. Congenital adrenal hyperplasia. N Engl J Med. 2003;349:776–88.
11. The Endocrine Society. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2010;95:4133–60.
12. Fernández B, Roldán M, Rodríguez A, Ezquieta B. Consejo genético en la hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa. An Pediatr. 2012;76:51–2.
13. Trapp CM, Speiser PW, Oberfield SE. Congenital adrenal hyperplasia: an update in children. Curr Opin Endocrinol Diabetes Obes. 2011;18:166–70.
14. Kim MS, Ryabets-Lienhard A, Geffner ME. Management of congenital adrenal hyperplasia in childhood. Curr Opin Endocrinol Diabetes Obes. 2012;19:483–8.
15. Cordeiro GV, Silva IN, Goulart EMA, Chagas AJ, Kater CE. Final height in congenital adrenal hyperplasia: the dilemma of hypercortisolism versus hyperandrogenism. Arq Bras Endocrinol Metabol. 2013;57:126–31.
16. Weil AP. La diversidad del sistema endocrino. En: Murray R, Bender D, Botham K, Kennelly P, Rodwell V, Weil P, editores. Harper bioquímica ilustrada. México D.F: McGrawHill; 2009. p. 429–32.
17. Alonso M, Ezquieta B. Hiperplasia suprarrenal congénita no clásica o tardía. Rev Esp Endocrinol Pediatr. 2012;3 Suppl 1:65–73.
18. White PC, Bachega TA. Congenital adrenal hyperplasia due to 21 hydroxylase deficiency: from birth to adulthood. Semin Reprod Med. 2012;30:400–9.
19. Labarta JI, de Arriba A, Ferrández Á. Hiperplasia suprarrenal congénita. Protoc diagn ter pediatr. 2011;1:117–28.
20. Chen Chen W, Xu Z, Sullivan A, Finkielstain GP, Van Ryzin C, Merke DP, et al. Junction site analysis of chimeric CYP21A1P/CYP21A2 genes in 21-hydroxylase deficiency. Clin Chem. 2012;58:421–30.
21. Licourt D, Pérez MM. Déficit de 21-hidroxilasa: aspectos actuales. Rev Ciencias Médicas. 2009;13:116–29.
22. New MI, Abraham M, Gonzalez B, Dumic M, Razzaghy-Azar M, Chitayat D, et al. Genotype-phenotype correlation in 1,507 families with congenital adrenal hyperplasia owing to
21-hydroxylase deficiency. Proc Natl Acad Sci U S A. 2013;110:2611–6.
23. Bidet M, Bellanné-Chantelot C, Galand-Portier M-B, Tardy V, Billaud L, Laborde K, 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;94:1570–8.
24. Haider S, Islam B, D’Atri V, Sgobba M, Poojari C, Sun L, et al. Structure-phenotype correlations of human CYP21A2 mutations in congenital adrenal hyperplasia. Proceedings of the National Academy of Sciences of the United States of America. 2013;110:2605–10.
25. Finkielstain GP, Chen W, Mehta SP, Fujimura FK, Hanna RM, Van Ryzin C, et al. Comprehensive genetic analysis of 182 unrelated families with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2011;96:E161–72.
26. Rodríguez-Arnao M, Rodríguez A, Badillo K, Velasco A, Dulín E, Ezquieta B. Déficit de 21-hidroxilasa: aspectos actuales. Rev Endocrinol Nutr. 2006;53:124–36.
27. al-Attia HM. Male pseudohermaphroditism due to 5 alpha-reductase-2 deficiency in an Arab kindred. Postgrad Med J. 1997;73:802–7.
28. Toscano J, Padilla J, Becerra L, Díaz M, Bañuelos O, Rivas F, et al. Hermafroditismo verdadero y secuencias del cromosoma Y. Implicaciones a propósito de dos casos. Rev Med Inst Mex Seguro Soc. 2008;46:539–42.
29. Falen J, Mio F, del Aguila C, Rojas M, Lu R, Meza M, et al. Características clínicas y hormonales del síndrome de insensibilidad a andrógenos. Rev. Perú. Pediatr. 2008;61:16–21.
30. Sepúlveda J, Sanguino L, Jaimes H. Hiperplasia adrenal congénita. Rev. Colomb. Obstet. Ginecol. 2001;28:52.
31. Hughes IA. Management of congenital adrenal hyperplasia. Arch Dis Child. 1988;63:1399–404.
32. Sanfilippo JS. Congenital adrenal hyperplasia pearls you should know–globally. J Pediatr Adolesc Gynecol. 2013;26:295.
33. Soriano L, Velázquez M. Hiperplasia suprarrenal congénita. Unidad de Endocrinología Infantil. Servicio de Pediatría. Fundación Jiménez Díaz. Madrid. Pediatr Integral. 2007;11:601–10.
34. Ghizzoni L, Cappa M, Vottero A, Ubertini G, Carta D, Di Iorgi N, et al. Relationship of CYP21A2 genotype and serum 17-hydroxyprogesterone and cortisol levels in a large cohort of Italian children with premature pubarche. Eur J Endocrinol. 2011;165:307–14.
35. Cánovas B, González-Albarrán O, Garcia R. Hiperplasia suprarrenal congénita. Medicine. 2000;8:1120–5.
36. New MI, Abraham M, Yuen T, Lekarev O. An update on prenatal diagnosis and treatment of congenital adrenal hyperplasia. Semin Reprod Med. 2012;30:396–9.
37. Botelho C, Novato I, Leite I, Nélio J. Neonatal screening for congenital adrenal hyperplasia. Rev. Assoc. Med. Bras. 2012;58:459–64.
38. Hayashi G, Faure C, Brondi MF, Vallejos C, Soares D, Oliveira E, et al. Weight-adjusted neonatal 17OH-progesterone cutoff levels improve the efficiency of newborn screening for congenital adrenal hyperplasia. Arq Bras Endocrinol Metab. 2011;55:632–7.
39. Kösel S, Burggraf S, Fingerhut R, Dörr HG, Roscher AA, Olgermöller B. Rapid second-tier molecular genetic analysis for congenital adrenal hyperplasia attributable to steroid 21-hydroxylase deficiency. Clin Chem. 2005;51:298–304.
40. Nordenström A, Wedell A, Hagenfeldt L, Marcus C, Larsson A. Neonatal screening for congenital adrenal hyperplasia: 17-hydroxyprogesterone levels and CYP21 genotypes in preterm infants. Pediatrics. 2001;108:e68.
41. Van der Kamp HJ, Oudshoorn CG, Elvers BH, van Baarle M, Otten BJ, Wit JM, et al. Cutoff levels of 17-alfa-hydroxyprogesterone in neonatal screening for congenital adrenal hyperplasia should be based on gestational age rather than on birth weight. J Clin Endocrinol Metab. 2005;90:3904–7.
42. Banks K, Pittock S, Sarafoglou K, Kyllo J, Thomas W. Cases of congenital adrenal hyperplasia missed by newborn screening in minnesota. JAMA. 2012;307:2371–4.
43. Sarafoglou K, Banks K, Gaviglio A, Hietala A, McCann M, Thomas W. Comparison of one-tier and two-tier newborn screening metrics for congenital adrenal hyperplasia. Pediatrics. 2012;130:1261–8.
44. Ryckman K, Cook D, Berberich S, Shchelochkov O, Copeland S, Berends S, et al. Replication of clinical associations with 17-hydroxyprogesterone in preterm newborns. J Pediatr Endocrinol Metab. 2012;25:301–5.
45. Cavarzere P, Samara-Boustani D, Flechtner I, Dechaux M, Elie C, Tardy V, et al. Transient hyper-17-hydroxyprogesteronemia: a clinical subgroup of patients diagnosed at neonatal screening for congenital adrenal hyperplasia. Eur J Endocrinol. 2009;161:285–92.
46. Hindmarsh PC. Management of the child with congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab. 2009;23:193–208.
47. 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;97:1881–3.
48. Fernandez-Balsells M, Muthusamy K, Smushkin G, Lampropulos JF, Elamin MB, Elnour N, et al. Prenatal dexamethasone use for the prevention of virilization in pregnancies at risk for classical congenital adrenal hiperplasia because of 21-hydroxylase (CYP21A2) deficiency: a systematic review and meta-analyses. Clin Endocrinol. 2010;73:436–44.
49. Mesogitis S, Daskalakis G, Papapetrou P, Mavroudis K, Papandroulaki F, Papantoniou N, et al. The effect on the fetal pituitary-adrenal axis of dexamethasone administration early in the second trimester of pregnancy. J Matern Fetal Neonatal Med. 2011;24:109–11.
50. New M. Vidication of prenatal diagnosis and treatment of congenital adrenal hyperplasia with low-dose dexametasone. Am J Bioeth. 2010;10:67–8.
51. Bryan SM, Honour JW, Hindmarsh PC. Management of altered hydrocortisone pharmacokinetics in a boy with congenital adrenal hyperplasia using a continuous subcutaneous hydrocortisone infusión. J Clin Endocrinol Metab. 2009;94:3477–80.
52. Moreira RP, Jorge AL, Gomes LG, Kaupert LC, Massud J, Mendonca BB, et al. Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clinics. 2011;66:1361–5.
53. Takasawa K, Ono M, Miyai K, Matsubara Y, Takizawa F, Onishi T, et al. Initial high dose hydrocortisone (HDC) treatment for 21-hydroxylase deficiency (21-OHD) does not affect linear growth during the first three years of life. Endocr J. 2012;59:1001–6.
54. Gomes LG, Madureira G, Mendonca BB, Bachega T. Mineralocorticoid replacement during infancy for salt wasting congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clinics. 2013;68:147–51.
55. Merke DP, Chrousos GP, Eisenhofer G, Weise M, Keil MF, Rogol AD, et al. Adrenomedullary displasia and hypofunction in patients with classic 21–hydroxylase deficiency. N Engl J Med. 2000;343:1362–8.
56. Loechner K, McLaughlin JT, Calikoglu AS. Alternative strategies for the treatment of classical congenital adrenal hyperplasia: pitfalls and promises. Int J Pediatr Endocrinol. 2010. Article ID 670960.
57. Romao R, Pippi J, Wherrett D. Update on the management of disorders of sex development. Pediatr Clin N Am. 2012;59:853–69.
58. Longui CA, Kochi C, Procópio LE, Rosa MB, Soares M, Ferreira E, et al. Near-final height in patients with congenital adrenal hyperplasia treated with combined therapy using GH and GnRHa. Arq Bras Endocrinol Metab. 2011;55:661–4.
59. Muthusamy K, Elamin MB, Smushkin G, Murad MH, Lampropulos JF, Elamin KB, et al. Clinical review: Adult height in patients with congenital adrenal hyperplasia: A systematic review and metaanalysis. J Clin Endocrinol Metab. 2010;95:4161–72.
60. Völkl T, Simm D, Beier C, Dörr H. Obesity among children and adolescents with classic congenital adrenal hyperplasia due to 21–hydroxylase deficiency. Pediatrics. 2006;117:e98–105.
61. Falhammar H, Filipsson H, Wedell A, Brismar K, Thorén M. Bone mineral density, bone markers and fractures in adult males with congenital adrenal hyperplasia. Eur J Endocrinol. 2013;168:331–41.
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