ESPE Abstracts

Background: Loss-of-function mutations of the androgen receptor (AR) gene result in androgen insensitivity syndrome (AIS) in 46,XY individuals, causing a disorder of sex development. AIS has a clinical continuum according to the resistance severity, being classified into three main categories: complete (CAIS), partial (PAIS), and mild (MAIS). The authors present a female phenotype patient with CAIS.

Case Report: An otherwise healthy 16-year-old girl was sent to a paediatric clinic for primary amenorrhea investigation. She had thelarche and pubarche at 10 and 12 years old, respectively, and a normal pubertal growth spurt. Her family history was unremarkable. Examination showed a female phenotype with breast Tanner stage IV, and thin and scarce pubic and axillary hair. There were no abdominal palpable masses, and the remaining observation was otherwise normal. Laboratory testing revealed LH 32,6 mUI/ml, FSH 9,5 mUI/ml, oestradiol 53 pg/ml, and total testosterone 0.13 ng/mL. Abdominal ultrasound showed no uterus or ovaries. Pelvic magnetic resonance imaging confirmed the uterus and ovaries' absence, unveiling a short and blind-ending vagina, as well as images consistent with testes adjacent to the inguinal canals' inner rings. As the whole constellation was suggestive of CAIS, she was then referred to our hospital center, where a paediatric multidisciplinary approach has taken place: endocrinology, surgery, genetics, and psychology. Genetic exams revealed a karyotype 46,XY, and a hemizygous likely pathogenic allelic variant in the AR gene (c.2086G>A). Gonadectomy was performed and histologic evaluation presented features of undescended testes, such as hyperplasia of Leydig cells and no spermatogenesis. There were no findings of malignancy. Hormone therapy with oestrogen was then started and gradually increased according to serial blood testing.

Discussion: In individuals with CAIS, there is no therapy able to prevent or reverse the effects that occur during embryogenesis. For this reason, management is focused on gonadectomy, hormone replacement, and psychological support for the patients and their families. Since these individuals have a normal growth spurt and feminize at the time of expected puberty, gonadectomy should be performed after sexual maturation is complete, given the risk of malignancy. After surgery, hormone replacement is ought to be started. These patients should be followed in a center with expertise, enabling a multidisciplinary approach, and always providing counseling, not only at diagnosis but also as required along the way.