Introduction: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in adult women. Syndrome is characterised by hiperandrogenism, oligo/amenorrhoea and polycystic ovary morphology in ultrasound. Clinical signs of the syndrome usually start already during adolescent years. Non-classic congenital adrenal hyperplasia (NCAH), caused by several mutations in CYP21A2 (6p21.3) gene, is the most common differential diagnosis for girls presented with symptoms of PCOS. Level of 17 OH progesterone and AKTH stimulation test is the main diagnostic tool. Nevertheless, genetic testing provides more accurate diagnosis.
Aim: To asess prevalence of NCAH causing alleles among adolescent patients with PCOS according to Rotterdam criteria.
Methods: 40 adolescent patients at least two years after menarche attending paediatric gyneacologist with PCOS according to Rotterdam criteria were included in the study. Hyperandrogenism was defined as Ferriman Gallway score more than seven or elevated testosterone, androstendione or DHEASO4 levels. DNA was extracted from venous blood using fenole chloroform methode. Genetic variations in the CYP21A2 gene were tested by using standart Multiplex Ligation-dependent Probe Amplification test (SALSA MLPA probemix P050-C1 CAH, MRC Holland), according to methodology established by producers. Research was approved by Central Medical Ethics Committee of Latvia.
Results: Median age of the study group was 16 (S.D. 1.4) years. Average score in Ferriman-Gallway scale was 10.8 (S.D. 6.3). We detected pathogenic variants in CYP21A2 for four patients, that constitutes 10% of the tested alleles. All discovered variants were in heterozygous state, that does not establish definitive diagnosis of NCAH. Two patients had c.-113 A>G, I172N (rs6475) and other two I2G (rs6467). Interestingly, all of the patients had normal 17 OH level below 2 ng/ml.
Conlusions: NCAH is one of the reasons for hiperandrogenism that is masked by clinical appereance of PCOS. Genetical testing is an important tool to distinguish between these two conditions. Prevalence of NCAH among PCOS patients in our study was lower than in literature (usually around 10%). Further studies in this area are required in order to test less prevalent mutations.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology