Endocrine Abstracts

JOINT2232

Background: Inherited 17βhydroxysteroid dehydrogenase type 3 (17βHSD3) deficiency causes 46, XY disorders of sexual development (DSD) with extremely variable clinical presentation: from female genitalia appearance to ambiguous genitalia (AG). 17βHSD3 enzyme is primarily expressed in the Leydig cells where it catalyses the conversion of 4-androstenedione (δ4) into testosterone (T). The 17βHSD enzyme family includes 14 isoforms which are active in multiple tissues controlling final steps of androgen and estrogen biosynthesis. T/δ4 ratio and genetic testing are necessary for early diagnosis.

Case Report: A 16-year-old girl was referred to our clinic due to primary amenorrhea. Her mother was from Poland and her father from Italy. In her past medical story, no relevant information was reported. No prenatal investigations were performed during her gestation. At her physical examination AG were observed: a 5.0- cm phallus, palpable gonads were found in both inguinal canals and a single perineal urethral opening with a short vagina. She exhibited facial hair and pubertal development corresponding to Tanner stage B1 and PH5. Virilization had occurred during puberty. Weight was 74.8 kg and height 172.3 cm. Laboratory tests showed: total basal T 268 ng/dl, basal δ4 911 ng/dl, basal T/δ4 0.29 (similar after HCG stimulation), normal DHEAS, 19OHP and slightly increased FSH, LH, 17β-estradiol, DHT levels. Karyotype: 46XY in all metaphases. Abdominal MRI revealed gonads located in the inguinal canals, cavernous body and seminal vesicles; no uterus or ovaries were identified. HSD17B3 gene sequencing showed the c.277+4A>T homozygous mutation within intron 3 resulting in a splicing defect. She identified herself as female and after psychological evaluation, according to her parents, she decided to maintain the female gender. Bilateral gonadectomy, feminizing genitoplasty, vaginal dilatation, additive mammoplasty and facial sculpture were performed. She is now on hormonal replacement therapy with estrogens.

Conclusion: The clinical manifestations of our patient emerged during puberty and sex assignment was guided by her self-determination. Previous data reported that female-to-male gender assignment occurs in 39-64% if diagnosis is made after virilization. However, diagnosis during puberty has become rarer: 10% of cases according to a French study. Over the time, the initial decision regarding sex rearing has shifted to male gender assignment. Nonetheless, data remain inconsistent: early orchiectomy seems may allow retention of a female gender identity. The process of sex assignment, recognizing predictors of gender identity development, and determining the optimal timing for surgery remain challenging in these patients.