Preponderance of ovarian tissue in a 47,XXY/46,XX patient with a predominant XXY cell line in the gonads

VENARA M; BASTIDA G; GRINSPON R P; AVILA S; CASTERA R; MAC DONELL M; PODESTA MIGUEL; DE CARLI C; CAMPAÑA R; REY R.; DRUT M; DIAZ S; BERGADA IGNACIO

Copenhaguen

Simposio; 6th International DSD Symposium; 2017

I-DSD

Background Clitoromegaly in a newborn or infant girl may be a manifestation of excess virilization in an XX patient, owing to abnormally elevated adrenal or gonadal androgen secretion, or a mild virilization in patients carrying an XY cell lineage, due to testicular dysgenesis or to specific defects in androgen synthesis or action. Case presentation: A female patient was referred to us for clitoromegaly at 1.1 years of age. She had a moderately enlarged clitoris (14 mm x 8 mm) with normal vulvae and separated urethral and vaginal orifices. No gonads were palpable. Ultrasonography showed the existence of a uterus, and a Fallopian tube with a structure compatible with gonad only in the right side. Congenital adrenal hyperplasia was ruled out based on normal 17OHP (0.10 ng/ml; NR 0.10-0.73). Basal serum steroid levels were uninformative (testosterone <10 ng/dl and estradiol <10 pg/mL), and elevated gonadotrophins with FSH predominance, LH 0.60 IU/L (NR 0.10-0.30), FSH 11.51 IU/L (NR 0.57-7.50). AMH was in the upper range of the female normal reference (45 pmol/l; NR 7-55) and hCG-stimulated testosterone was higher than expected for a girl (79 ng/dl), suggesting the presence of scarce testicular tissue. Peripheral blood karyotype was 47,XXY[34]/46,XX[18]. Ovotesticular DSD was suspected. Laparoscopy confirmed the presence of uterus and Fallopian tubes. Unexpectedly, histology of both gonadal biopsies exclusively showed the presence of bilateral ovaries with abundant primordial and primary follicles (Figure 1a). Fluorescence in situ hybridization (FISH) for the centromeric regions of the X (DXZ1) and Y (DYZ23) chromosomes from both gonads described a clear predominance of XXY cell lines; XXY[74%]/XX[26%] in the right gonad and XXY[65%]/XX[35%] in the left gonad (Figure 1b). Conclusion and Discussion: We report the unexpected finding of a clear preponderance of ovarian tissue in a 47,XXY/46,XX patient with a predominant XXY cell line in gonadal cells. On the other hand, this case poses a clinical dilemma regarding the decision whether or not to perform gonadectomy, owing to the presence of a Y chromosome. Although tumor risk is low in ovotesticular DSD with a 46,XX karyotype, scarce information is available in patients with ovotesticular DSD with a Y chromosome.