title: Superior discriminating value of ACTH-stimulated serum 21-deoxycortisol in identifying heterozygote carriers for 21-hydroxylase deficiency.
abstract: BACKGROUND
  Congenital adrenal hyperplasia caused by classic 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder with a high prevalence of asymptomatic heterozygote carriers (HTZ) in the general population, making case detection desirable by routine methodology. HTZ for classic and nonclassic (NC) forms have basal and ACTH-stimulated values of 17-hydroxyprogesterone (17OHP) that fail to discriminate them from the general population. 21-Deoxycortisol (21DF), an 11-hydroxylated derivative of 17OHP, is an alternative approach to identify 21OHD HTZ.
  
  
  OBJECTIVE
  To determine the discriminating value of basal and ACTH-stimulated serum levels of 21DF in comparison with 17OHP in a population of HTZ for 21OHD (n = 60), as well as in NC patients (n = 16) and in genotypically normal control subjects (CS, n = 30), using fourth generation tandem mass spectrometry after HPLC separation (LC-MS/MS).
  
  
  RESULTS
  Basal 21DF levels were not different between HTZ and CS, but stimulated values were increased in the former and virtually nonresponsive in CS. Only 17·7% of the ACTH-stimulated 21DF levels overlapped with CS, when compared to 46·8% for 17OHP. For 100% specificity, the sensitivities achieved for ACTH-stimulated 21DF, 17OHP and the quotient [(21DF + 17OHP)/F] were 82·3%, 53·2% and 87%, using cut-offs of 40, 300 ng/dl and 46 (unitless), respectively. Similar to 17OHP, ACTH-stimulated 21DF levels did not overlap between HTZ and NC patients. A positive and highly significant correlation (r = 0·846; P < 0·001) was observed between 21DF and 17OHP pairs of values from NC and HTZ.
  
  
  CONCLUSIONS
  This study confirms the superiority of ACTH-stimulated 21DF, when compared to 17OHP, both measured by LC-MS/MS, in identifying carriers for 21OHD. Serum 21DF is a useful tool in genetic counselling to screen carriers among relatives in families with affected subjects, giving support to molecular results.
authors.affiliation: Steroids Laboratory, Adrenal and Hypertension Unit, Division of Endocrinology and Metabolism, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Flávia A
authors.initials: FA
authors.lastname: Costa-Barbosa
authors.forename: Vânia F
authors.initials: VF
authors.lastname: Tonetto-Fernandes
authors.forename: Valdemir M
authors.initials: VM
authors.lastname: Carvalho
authors.forename: Odete H
authors.initials: OH
authors.lastname: Nakamura
authors.forename: Vivian
authors.initials: V
authors.lastname: Moura
authors.forename: Tânia A S S
authors.initials: TA
authors.lastname: Bachega
authors.forename: José G H
authors.initials: JG
authors.lastname: Vieira
authors.forename: Claudio E
authors.initials: CE
authors.lastname: Kater
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D000324:Adrenocorticotropic Hormone / Q000737:chemistry*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid; D003350:Cortodoxone / Q000097:blood*; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: C003556:21-deoxycortisol; D000324:Adrenocorticotropic Hormone; D013255:Steroid 21-Hydroxylase; D003350:Cortodoxone