Non-classic 21-Hydroxylase deficiency among women with PCOS: Study from western Indian population

Non-classic 21-hydroxylase deficiency (NCCAH) is one of the most common autosomal recessive disorders and is caused due to mutations in CYP21A2 gene with 20-50% residual enzyme activity. These present with subtle clinical features of hyperandrogenism like hirsutism, menstrual irregularities and infertility, and hence, are differential diagnoses of polycystic ovary syndrome (PCOS). Older studies from India have shown NCCAH to be present amongst 1-5% of women with PCOS or hirsutism. However, the diagnosis of these patients was based on clinical and biochemical characteristics without genetic confirmation. The aim of this study was to estimate the prevalence of NCCAH amongst women with PCOS from western India.

All women > 18 years of age diagnosed with PCOS based Rotterdam criteria will be screened for inclusion in the study. Patients will be called during the follicular phase of the menstrual cycle if having regular cycles or on a random day if the patient is amenorrhoic blood samples will be drawn for FSH, LH, prolactin, testosterone and TSH following which Inj. Tetracosactide acetate 250 mcg of (ACTH 1-24) will be given intramuscularly and blood samples will be drawn at an interval of 60 mins for steroid panel by LC-MS/MS including 11-deoxycortisol, cortisol, 11-deoxycorticosterone, corticosterone, Progesterone, 17-hydroxyprogesterone, 21-Deoxycortisol, androstenedione and Testosterone, cortisone, DHEA and DHEAS. Venous blood sample will also be taken for Genetic analysis for CYP21A2 gene for targeted next generation sequencing. The values of steroid panel so obtained will be analysed to evaluate the differences in patients with PCOS vs those with NCCAH.