title: Neonatal screening for congenital adrenal hyperplasia.
abstract: Congenital adrenal hyperplasia (CAH) caused by steroid 21-hydroxylase deficiency occurs in 1:16,000-1:20,000 births. If not promptly diagnosed and treated, CAH can cause death in early infancy from shock, hyponatremia and hyperkalemia. Affected girls usually have ambiguous genitalia but boys appear normal; therefore, newborn babies are commonly screened for CAH in the US and many other countries. By identifying babies with severe, salt-wasting CAH before they develop adrenal crises, screening reduces morbidity and mortality, particularly among affected boys. Diagnosis is based on elevated levels of 17-hydroxyprogesterone, the preferred substrate for steroid 21-hydroxylase. Initial testing usually involves dissociation-enhanced lanthanide fluorescence immunoassay that has a low positive predictive value (about 1%), which leads to many follow-up evaluations that have negative results. The positive predictive value might be improved by second-tier screening using DNA-based methods or liquid chromatography followed by tandem mass spectrometry, but these methods are not widely adopted. Cost estimates for such screening range from US$20,000 to $300,000 per life-year saved. In babies with markedly abnormal screen results, levels of serum electrolytes and 17-hydroxyprogesterone should be immediately determined, but the most reliable way to diagnose CAH is measurement of levels of steroid precursors after stimulation with cosyntropin.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9063, USA. perrin.white@utsouthwestern.edu
authors.forename: Perrin C
authors.initials: PC
authors.lastname: White
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood / Q000175:diagnosis*; D004573:Electrolytes / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening / Q000191:economics
chemical_list: D004573:Electrolytes; D019326:17-alpha-Hydroxyprogesterone
references.citation: J Pediatr. 2005 Oct;147(4):493-8
references.pmid: 16227036
references.citation: Eur J Pediatr. 1996 Nov;155(11):928-31
references.pmid: 8911890
references.citation: J Clin Endocrinol Metab. 2007 Jul;92(7):2581-9
references.pmid: 17456574
references.citation: Eur J Endocrinol. 2005 Jun;152(6):869-74
references.pmid: 15941926
references.citation: J Pediatr. 1989 Mar;114(3):400-4
references.pmid: 2784166
references.citation: Pediatrics. 2006 May;117(5 Pt 2):S287-95
references.pmid: 16735255
references.citation: Adv Exp Med Biol. 2002;511:107-19; discussion 119-20
references.pmid: 12575758
references.citation: Arch Pediatr Adolesc Med. 2001 Sep;155(9):1038-42
references.pmid: 11529806
references.citation: Arch Pediatr Adolesc Med. 1999 Dec;153(12):1272-8
references.pmid: 10591305
references.citation: Clin Chem. 2006 Aug;52(8):1559-67
references.pmid: 16777916
references.citation: Pediatrics. 1988 Jun;81(6):866-74
references.pmid: 3259306
references.citation: Clin Chem. 2002 Jun;48(6 Pt 1):818-25
references.pmid: 12028996
references.citation: Mol Diagn. 2001 Sep;6(3):193-9
references.pmid: 11571713
references.citation: Horm Res. 2001;55(6):271-7
references.pmid: 11805430
references.citation: Pediatrics. 1998 Apr;101(4):E11
references.pmid: 9521977
references.citation: Clin Chem. 2005 Feb;51(2):298-304
references.pmid: 15608154
references.citation: J Clin Endocrinol Metab. 2005 Jul;90(7):3904-7
references.pmid: 15797960
references.citation: Pediatrics. 2006 Jun;117(6):1915-21
references.pmid: 16740831
references.citation: Horm Res. 2008;69(4):253-6
references.pmid: 18204274
references.citation: Eur J Endocrinol. 2004 Nov;151 Suppl 3:U71-5
references.pmid: 15554889
references.citation: Cytogenet Genome Res. 2008;123(1-4):131-41
references.pmid: 19287147
references.citation: J Clin Endocrinol Metab. 2002 Sep;87(9):4106-10
references.pmid: 12213856
references.citation: Pediatrics. 1996 Sep;98(3 Pt 1):362-7
references.pmid: 8784357
references.citation: N Engl J Med. 2003 Aug 21;349(8):776-88
references.pmid: 12930931
references.citation: Public Health Genomics. 2009;12(2):67-72
references.pmid: 19039250
references.citation: Endocrinol Metab Clin North Am. 2001 Mar;30(1):15-30
references.pmid: 11344933
references.citation: Curr Opin Pediatr. 1997 Aug;9(4):419-23
references.pmid: 9300201
references.citation: Cochrane Database Syst Rev. 2007 Jul 18;(3):CD003935
references.pmid: 17636741
references.citation: J Inherit Metab Dis. 2007 Aug;30(4):430-8
references.pmid: 17616847
references.citation: J Clin Endocrinol Metab. 1983 Aug;57(2):320-6
references.pmid: 6306039
references.citation: J Clin Endocrinol Metab. 1999 Mar;84(3):960-6
references.pmid: 10084579
references.citation: J Clin Endocrinol Metab. 2002 Sep;87(9):4048-53
references.pmid: 12213842
references.citation: J Clin Endocrinol Metab. 2002 Feb;87(2):735-41
references.pmid: 11836313
references.citation: Endocr J. 1998 Aug;45(4):493-7
references.pmid: 9881898
references.citation: Early Hum Dev. 1997 Oct 10;49(3):225-33
references.pmid: 9378083
references.citation: Hum Mol Genet. 1996 Dec;5(12):2039-48
references.pmid: 8968761
references.citation: Pediatrics. 1996 Jan;97(1):100-2
references.pmid: 8545200
references.citation: Am J Hum Genet. 1985 Jul;37(4):650-67
references.pmid: 9556656
references.citation: Clin Chem. 2004 Mar;50(3):621-5
references.pmid: 14656905
references.citation: Horm Res. 2005;63(1):22-8
references.pmid: 15627780
references.citation: Arch Pediatr Adolesc Med. 2008 Sep;162(9):870-6
references.pmid: 18762606
references.citation: J Pediatr. 1997 Jan;130(1):128-33
references.pmid: 9003862
references.citation: J Clin Endocrinol Metab. 1999 May;84(5):1505-9
references.pmid: 10323369
references.citation: J Clin Endocrinol Metab. 1977 Nov;45(5):1003-8
references.pmid: 925125
references.citation: Anal Chem. 2008 Dec 1;80(23):9363-8
references.pmid: 19551952
references.citation: Pediatrics. 2001 Dec;108(6):1320-4
references.pmid: 11731654
references.citation: J Clin Endocrinol Metab. 1999 Mar;84(3):838-43
references.pmid: 10084558
references.citation: J Child Neurol. 1991 Oct;6(4):306-12
references.pmid: 1940131
references.citation: Clin Chem. 1990 Sep;36(9):1667-72
references.pmid: 2208708
references.citation: Nat Genet. 2004 Mar;36(3):228-30
references.pmid: 14758361
references.citation: Horm Res. 2007;67(6):284-91
references.pmid: 17199092
references.citation: J Clin Endocrinol Metab. 2003 Dec;88(12):5790-4
references.pmid: 14671170
references.citation: Mol Endocrinol. 1991 May;5(5):685-92
references.pmid: 2072928
references.citation: Pediatrics. 1998 Apr;101(4 Pt 1):583-90
references.pmid: 9521938
references.citation: J Inherit Metab Dis. 2007 Aug;30(4):585-92
references.pmid: 17643193
references.citation: Steroids. 2006 Jun;71(6):450-8
references.pmid: 16569417
references.citation: Eur J Pediatr. 2007 Jan;166(1):1-4
references.pmid: 17024350
references.citation: Pediatr Res. 2004 Nov;56(5):701-5
references.pmid: 15371568
references.citation: Endocr Rev. 2000 Jun;21(3):245-91
references.pmid: 10857554
references.citation: Acta Paediatr Jpn. 1992 Apr;34(2):126-33
references.pmid: 1621517
references.citation: Clin Chem. 1992 Sep;38(9):1830-7
references.pmid: 1526021
references.citation: J Clin Endocrinol Metab. 2004 Aug;89(8):3687-93
references.pmid: 15292289
references.citation: J Clin Endocrinol Metab. 2005 Feb;90(2):775-8
references.pmid: 15572419
references.citation: Pediatrics. 2006 Aug;118(2):e488-500
references.pmid: 16882788
references.citation: Acta Paediatr Scand. 1990 Feb;79(2):168-75
references.pmid: 2321478
references.citation: Arch Dis Child. 1994 Mar;70(3):214-8
references.pmid: 8135566