Background: Androgen insensitivity syndrome (AIS) is an X-linked hereditary disease with AR gene loss-of-function mutations in 46,XY patients. They undergoes poor development of secondary sex characteristics, except for breast development at puberty. AIS patients are prone to develop germ cell cancer, even though with lower incidence than in dysgenetic gonads secondary to defects in organogenesis.
Case presentation: We described a 3-years-old girl referred because growth acceleration and progressive breast development. She had fully developed female phenotype without sexual ambiguity. Pelvic ultrasound (PU) revealed Mullerian structures and two gonads resembling ovaries. Physical examination revealed: Height (H): 116.3 cm (HSDS: +3.8), Bone age (BA): 7 years, Breast development (Tanner IV) and scarce pubic hair. Endocrine studies revealed serum basal pubertal oestradiol (25 pg/ml) but pre-pubertal testosterone, LH and FSH levels failing to respond to acute GnRH stimulation. Diagnosis of pseudo precocious puberty (PPPUB) secondary to excessive steroid production was made. The source of the abnormal sex steroids was undetermined. At 8.2 years she was readmitted to the Hospital. H: 148.1 cm (HSDS: +4), BA: 16 years. The diagnosis of central precocious puberty was made. However; the aetiology of her early sexual development remained undetermined. Patient was lost in follow-up until 20y of age. H: 150 cm (HSDS: −1.75) Referred because of primary amenorrhea. CAIS diagnosis was suspected. PU discarded the presence of Mullerian structures. Karyotype was 46,XY. Molecular studies revealed a loss-of-function mutation in the androgen receptor gene, c.1972delC (p.Q658fs*2). Bilateral gonadectomy was performed. Histologic study of both gonads showed abundant signs of testicular dysgenesis and in one, a tubular structure with cylindrical epithelium, characteristic of a Sertoli cell tumour (SCT), was observed. Positive inmunoexpression of CYP11A1 and CYP19 aromatase was found only in the SCT.
Conclusion: In conclusion, we are reporting for the first time PPPU in an AIS patient. Early sex development can be secondary to oestrogen synthesis by a SCT.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology