Correlation between genotype and hormonal levels in heterozygous mutation carriers and non carriers of 21-OH deficiency

Congenital Adrenal Hyperplasia, both in its classic (CCAH) and in non classic form (NCAH), is a morbid condition sustained by the absent or reduced function of one of the enzymes involved in cortisol biosynthesis – mainly 21 hydroxylase – associated with different levels of clinical androgenization. In a wide group of relatives of patients affected by CCAH and NCAH (N= 222) or healthy volunteers (N= 30) a clinical, hormonal and genetic evaluation had been performed in order to differentiate the condition of heterozygous mutation carrier or not of any among 21 hydroxylase gene (CYP 21) mutations. This study shows that clinical presentation and basal 17α-OHP are not able to differentiate between heterozygous carriers and non carriers whereas 17α-OHP value after ACTH bolus is significantly different between heterozygous carriers and non carriers: p<0.001 with a “cut-off” value of 3 ng/ml (90% sensitivity and 74,3% specificity). Moreover, our data indicate that 17α-OHP response to ACTH may be a useful tool to select subjects for genetic analysis.