Abstract 137

Abstract

Introduction: Aromatase deficiency might produce “non-classic” phenotypes due to variable degrees of residual enzyme activity. Aim: To describe clinical, biochemical, radiological, management and outcomes in patients with 46 XX genetically proven aromatase deficiency from our center and systematic review the hormonal profile of patients with pathogenic variants of CYP19A1. Methods: This retrospective study was conducted at Seth G.S. Medical college and K.E.M. Hospital, which includedall patients with genetically diagnosed aromatase deficiency. We searched the PubMed database with no date restrictions until October 2022 with the following search items “(aromatase deficiency) AND (46, XX OR ovaries). 35 46XX DSD patients harboring CYP19A1 pathogenic variants from the literature and seven patients from our center, a cohort of 42 patients was considered for final analysis. Results: Our cohort - Out of seven patients, three (3/7) presented in prepubertal age [0.03 (0.019-0.75) years], three (3/7) in pubertal age [12.7 (9.7-13.0) years] and one (1/7) in adulthood (16 years). Atypical genitalia are the most common presenting complaint (6/7) and is present in all the seven patients (Prader II- 1/7, Prader III- 4/7, Prader IV- 2/7), one patient presented with absent secondary sexual characters.6/7 patients were reared as female child and one child was initially reared as male and switched to female after diagnosis. None of the children had gender dysphoria. Maternal virilization was evident in four patients (4/7). One patient (1/4) had spontaneous breast development with regular menses. Ultrasound pelvis shows cystic ovaries (2/7), hypoplastic ovaries (3/7) and normal ovaries (2/7). Systematic review of hormonal profile: Patients are categorized in to four subgroups [0-0.5 yrs, 0.6-8 yrs, 8.1-13.0 yrs, >13.1 yrs]. All the values are expressed in median (IQR). Follicular stimulating hormone levels (mIU/ml) were consistently elevated in all the subgroup patients [37.4 (17.1-67.3), 21.7 (12.2-38.1), 14.2 (8.8-49.9), 28.4 (18.8-45.2) respectively]. Luteinizing hormone (LH) levels are predominantly elevated in group 1 and group 4 patients [4.9 (1.4-17.7), 1.0 (0.3-2.7), 1.5 (1.3-11.5), 23.7 (16.2-33.9)]. Testosterone (ng/ml) levels [0.37 (0.09-0.9), 0.07 (0.04-0.1), 0.29 (0.1-0.9), 0.6 (0.4-0.8)] and androstenedione [0.63 (0.17-1.4), 0.30 (0.2-0.4), 1.44 (0.8 -1.5), 2.8] have a biphasic pattern similar to LH, elevated during minipuberty and puberty. Estradiol levels are constant in all the subgroups [10 (3.0-11.5), 10 (5.0-18.6), 46.9 (n = 1), 19.4 (8.7-28.1)]. Conclusion: Ambiguous genitalia, maternalantenatal virilization, and markedly elevated FSH levels are important diagnostic indicators. Absence of multicystic ovaries and maternal virilization should not rule out the diagnosis.