MON-197 - Late-Presenting 46,XY Disorder of Sex Development Due to 17Β-Hydroxysteroid Dehydrogenase Type 3 Deficiency with Complex Endocrine and Psychosocial Outcomes.

Background: 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency is a rare autosomal recessive cause of 46,XY disorder of sex development (DSD) characterized by impaired conversion of androstenedione to testosterone. Delayed diagnosis and fragmented care can significantly affect long-term outcomes.

Case: A patient assigned female at birth presented at age 12 with clitoromegaly (6 cm) and virilization. Puberty was Tanner stage III for breasts and pubic hair. Imaging revealed an absent uterus and ovaries, structures resembling seminal vesicles, and bilateral inguinal masses consistent with undescended testes. Pelvic ultrasound showed a 2-cm vaginal cuff without Müllerian structures. Genetic testing revealed compound heterozygous mutations in HSD17B3 consisting of one known missense and one novel splice-site variant. ACTH testing revealed elevated androstenedione (804→818 ng/dL), DHEA (292→490 ng/dL), and 11-deoxycortisol (172→398 ng/dL) with appropriate cortisol response (4.0→29.4 mcg/dL). Testosterone was 222 ng/dL, estradiol 32 pg/mL, LH 18.9 mIU/mL, and FSH 17.8 mIU/mL. Following a multidisciplinary discussion with the patient and guardian's consent, female gender was affirmed. The patient underwent gonadectomy with leuprolide and estrogen therapy. Estrogen was discontinued at age 17 due to weight concerns and psychiatric comorbidity, and the patient was lost to endocrine follow-up.
At age 30, the patient re-established care, reported living as male for 15 years, and demonstrated hypergonadotropic hypogonadism (FSH 48 mIU/mL, LH 41 mIU/mL) with low total testosterone (19 ng/dL) and estradiol (25 pg/mL). Testosterone therapy normalized gonadotropins and androgen levels. The course was complicated by osteoporosis, obesity, hyperlipidemia, hypertension, and severe psychiatric illness.

Discussion: Adult management of 17β-HSD3 deficiency emphasizes lifelong sex steroid replacement aligned with gender identity, targeting physiologic testosterone or estradiol levels, regular bone mineral density monitoring, cardiometabolic risk assessment/mitigation, fertility/sexual counseling, and psychosocial support. Gonadectomy is recommended when gonads are retained due to malignancy risk. This case demonstrates how a disrupted transition to adult endocrinology can result in prolonged hypogonadism with preventable morbidity.

Conclusion: This case highlights 17β-HSD3 deficiency presented with pubertal virilization, early gonadectomy, adult gender transition, and long-term sequelae. Emphasizing the importance of early diagnosis, structured transition, and guideline-aligned longitudinal multidisciplinary care.

Reference: Hughes IA, et al. LWPES Consensus Group, ESPE Consensus Group: Consensus statement on management of intersex disorders. Arch Dis Child 2006;91:554–563.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*