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Superior discriminating value of ACTH‐stimulated serum 21‐deoxycortisol in identifying heterozygote carriers for 21‐hydroxylase deficiency
Author(s) -
CostaBarbosa Flávia A.,
TonettoFernandes Vânia F.,
Carvalho Valdemir M.,
Nakamura Odete H.,
Moura Vivian,
Bachega Tânia A. S. S.,
Vieira José G. H.,
Kater Claudio E.
Publication year - 2010
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2010.03871.x
Subject(s) - medicine , congenital adrenal hyperplasia , endocrinology , 21 hydroxylase , basal (medicine) , population , asymptomatic , heterozygote advantage , adrenocorticotropic hormone , chemistry , genotype , biochemistry , gene , environmental health , hormone , insulin
Summary 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. Conclusion 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.