Endocrine Abstracts

Introduction: Androgen insensitivity syndrome rare X linked disorder that is typically characterized by evidence of feminization of the external genitalia at birth, abnormal secondary sexual development in puberty, and infertility in individuals with a 46,XY karyotype. Complete androgen insensitivity syndrome (CAIS) usually is recognized only at the teenage age due to primary amenorrhea. Recently, gonadectomy for patients with CAIS are postponed due to a mild risk of malignancy.

Case report: This report refers 15.3-year-old patient, assigned as female, who presents with primary amenorrhea. Physical examination observed the female appearance and normal external genitalia with a 4 cm length of vagina, puberty maturation was evaluated B4P1-2 (by Tanner stage). Laboratory examination showed high levels of testosterone and anti-Müllerian hormone, and normal levels of gonadotropins and estradiol; the uterus was absent but observed bilateral solid formations in the pelvic MRI. Chromosome analysis confirmed a 46,XY karyotype. Sanger sequencing of AR (NM_000044.6) gene from blood leukocytes DNA was performed and a novel hemizygous likely pathogenic variant c.232_241del p.(Gln78ArgfsTer94) was detected. This variant also confirmed in the testicular tissue DNA. The diagnostic laparoscopy was performed, and histological analysis of the bilateral gonads showed the immature testis tissue with Sertoli and Leydig’s cells. During laparoscopy, also open processus vaginalis was found. Contralateral inguinal hernia was operated on in infant age. The CAIS was confirmed. Gender was assigned as female, but gonadectomy was postponed and hormonal therapy by estrogen did not initiate due to normal level of estrogen and bone mineral density (BMD).

Conclusions: Historically, the gonadectomy for individuals with CAIS was performed after conforming diagnosis at various ages to avert the risk of gonadal malignancy. Recently, gonadectomy is postponed until early adulthood age (25–30 y.o.). Postponed gonadectomy prevents postsurgical hypogonadism which might have negative effects on cardiovascular health and BMD [1].

Reference: 1. Weidler EM, Linnaus ME, Baratz AB, Goncalves LF, Bailey S, Hernandez SJ, Gomez-Lobo V, van Leeuwen K. A Management Protocol for Gonad Preservation in Patients with Androgen Insensitivity Syndrome. J Pediatr Adolesc Gynecol. 2019 Dec;32(6):605-611. doi: 10.1016/j.jpag.2019.06.005. Epub 2019 Jun 21.