Background: Complete androgen insensitivity syndrome (CAIS) is an X-linked recessive disorder of sex development (DSD) where affected individuals are phenotypically female but have a XY karyotype and testes. With increasing age there is an increased risk of malignant gonadal change, with incidence rates variously reported from 3.6 to 14%. Consequently, gonadectomy is recommended either during childhood or after puberty is complete, although there is no consensus on the optimal timing for this procedure.
Objective and hypotheses: To establish the frequency of histological abnormalities in CAIS in relation to the age and timing of gonadectomy.
Method: Data was collected from the Cambridge DSD database on patients with CAIS (n=225; age range 388 years) undergoing gonadectomy, including age and pubertal status at gonadectomy, gonadal histology, and immunohistochemistry.
Results: Evaluable data was obtained from 139 patients. At time of gonadectomy, median (range) age=12.8 years (18 days 68 years); pubertal status n=63 pre-puberty; 70 post-puberty; six unknown. Gonadal abnormalities were reported in 26 cases: benign tumour n=18 (seven sertoli cell adenoma (SCA); eight testicular hamartoma (TH); two mixed SCA/TH; and one sex cord tumour with annular tubules)/malignant changes n=8 (one Sertoli cell tumour; one sex cord tumour; one seminoma; and five intra-tubular germ cell neoplasia). Pre-malignant changes were all confirmed on immunohistochemistry. In malignant/pre-malignant cases, median (range) age at gonadectomy=18 years (168 years) with two out of eight individuals undergoing this procedure before puberty.
Conclusion: In this large case-series of CAIS patients undergoing gonadectomy evidence of malignant or pre-malignant change was found in 5.7% of cases and occurred before puberty in 1.4%. Consequently, it may be advisable to perform gonadectomy before puberty in those who present in early childhood, if there is a lack of tumour marker evidence to exclude malignancy.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology