ESPE Abstracts

Introduction: Androgen Insensitivity Syndrome (AIS) is the most common cause of Differences of Sexual Development (DSD) in 46, XY individuals. It is an X-linked genetic disease caused by allelic variants in the Androgen Receptor Gene (Xq11-12). Methods: Patients with clinical suspicion of AIS performed hormonal serum measurements (LH, FSH, estradiol, testosterone) and molecular sequencing of the AR gene, including exons and the 5’UTR region. Psychosexual variables (gender identity, gender role and sexual orientation) were evaluated through psychological questionnaires and tests. Histopathological and immunostainining of CD240 and OCT3/4 studies were carried out for all individuals submitted to gonadectomy.

Results: This cohort is made up of 64 individuals: CAIS (n=25) and PAIS (n=39), from 46 different families. The inguinal hernia was the first clinical presentation in 35% of CAIS. Among the PAIS, 20 (52%) were assigned as females at birth, while 18 (48%) as male. Among PAIS, the degree of external genitalia virilization (Sinnecker score) influenced sex assignment (P<0.01). Standing final height and weight were similar between PAIS and CAIS. The bone mineral apparent density (BMAD) by DXA was similar between individuals who had or not gonadectomy as well as between CAIS and PAIS. Furthermore, gender identity in adulthood, gender role at childhood, and sexual orientation agreed with sex assignment in virtually all cases of both PAIS and CAIS. No gender change was observed. Molecular diagnosis was obtained in 96% of CAIS and 87% of PAIS. Ten novels AR variants (4 in CAIS - 2 small deletions, one missense and one at splicing site and PAIS - 5 missense and two synonymous (both causing a new exonic splicing site leading to an aberrant AR protein). LH ranged from 9 to 48 UI/l (mean 19), testosterone from 190 to 1500 ng/dl (mean 438), without phenotype differences. Gonadal tumors were identified in 3 out 25 (12%) among CAIS. There were two cases of Seminoma and a rare case of a borderline serous tumor. All CAIS tumors were identified after puberty. Among PAIS, there were 2 cases of NICG (at 3 and 19 years of age).

Conclusion: Hormonal levels did not enable us to differ from PAIS and CAIS. Inguinal hernia is the commonest clinical presentation of AIS. External genitalia appearance in PAIS influenced sex assignment. The psychosexual development in AIS is usually aligned with sex assignment. There is a risk of gonadal tumors in CAIS, especially after puberty, which is not low enough to be ignored.