The prevalence of non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Russian women with hyperandrogenism

Abstract

The aim of the study was to determine the prevalence of non-classic congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase (21-OH) deficiency among hyperandrogenic women in a Russian population and to evaluate diagnostic value of basal serum 17-hydroxyprogesterone (17-OHP) level to diagnose this disease. A total of 800 consecutive Caucasian women presenting with elevation of at least one serum androgen and/or manifestation of one of the clinical androgenic symptoms were prospectively recruited and evaluated by basal 17-OHP. The diagnosis of NCAH due to 21-OH deficiency was considered in patients when basal level exceeded 5.0 nmol/L and CYP21A2 gene mutation analysis was performed in this case. Eight (1.0%) of the patients had NCAH due to 21-OH deficiency confirmed by genotyping. These women had a V281L mutation: five homozygous and three compound heterozygous with genotypes V281L/P453S, V281L/I2splice and V281L/I2splice. One patient was diagnosed with NCAH (genotype V281L/I2splice) before the study and was excluded from the analysis. Thus, the unbiased prevalence of NCAH was 0.9%. The 17-OHP basal level ranges from 16.8 to 17.7 nmol/L predicted NCAH with 100% sensitivity and 100% specificity.

17-Hydroxyprogesterone Response to Standard Dose Synacthen Stimulation Test in CYP21A2 Heterozygous Carriers and Non-carriers in Symptomatic and Asymptomatic Groups: Meta-analyses

“…These studies were carried out in Europe, the United States of America, and Russia. Three studies were carried out in Greece ( 15 , 30 , 31 ), three in the United States of America ( 18 , 32 , 33 ), two in Italy ( 34 , 35 ), two in Brazil ( 36 , 37 ), two in France ( 38 , 39 ), one in Turkey ( 21 ), one in Russia ( 40 ) and one in Israel ( 41 ). CYP21A2 mutation analysis and basal and/or stimulated 17-OHP measurements were available in all study subjects.…”

“…Among the included studies, two were added to the relevant sub-analysis since they only included basal 17-OHP measurements ( 31 , 40 ). Two different control groups were identified in the included studies; a mutation-free asymptomatic healthy volunteer group (asymptomatic heterozygous vs. asymptomatic mutation-free healthy control), and a mutation-free but clinically symptomatic volunteer group (symptomatic heterozygous vs. symptomatic mutation-free control).…”

“…Firstly, a genetic analysis was performed in all the subjects. Secondly, almost all 17-OHP measurements were performed by using the same hormone measurement method (RIA), with the exception of two studies ( 37 , 40 ).…”

EMQN best practice guidelines for molecular genetic testing and reporting of 21-hydroxylase deficiency

“…The genotype/phenotype correlation decreases with diminished severity of the disease [ 71 , 72 ] or depends on the patient’s background with respect to other genes regulating androgen and oestrogen metabolism. In that context it is of note that Grodnitskaya and Kurtser [ 73 ] published only recently that out of 800 women with hyperandrogenism only 1% had non-classical CAH due to 21-OH deficiency. There are also many papers reporting symptomatic patients with clinical signs of hyperandrogenism (hirsutism, precocious puberty, cycle abnormalities in women) and only heterozygous 21-OH function impairing variants and that heterozygotes are more likely to have signs of androgen excess than would genetically-unaffected subjects [ 74 – 76 ].…”