(136) Voice Deepening and Primary Amenorrhea in an Adolescent Female: A Case of 17-Beta-Hydroxysteroid Dehydrogenase Type 3 Deficiency in a 46XY Individual

Background: Disorders of Sexual Development (DSD) occur approximately 1 in 20,000 live births. Common causes of DSD include androgen insensitivity syndrome, gonadal dysgenesis, and 5-reductase deficiency. 17β-Hydroxysteroid Dehydrogenase 3 (17β-HSD3) deficiency, estimated to affect 1/147,000 individuals, is a rare autosomal recessive disorder due to a mutation in the HSD17B3 gene which is vital for the conversion of androstenedione to testosterone. This condition affects XY individuals where impaired testicular production of testosterone leads to either a phenotypic female or ambiguous genitalia at birth.

Case: A 15-year-old phenotypically female patient presented to pediatric gynecology due to primary amenorrhea, lack of breast development, and subtle voice deepening. Initial evaluation revealed an absent uterus on ultrasound and elevated LH, FSH, 17-OHP, androstenedione, and testosterone. The testosterone-to-androstenedione ratio was 0.1. Subsequent genetic testing confirmed 17β-HSD3 deficiency and sex reversal. An MRI was performed to assess location of internal gonads and discussions were had regarding gonadectomy. Interestingly, there is no standardization regarding gonadectomy in this specific patient population. Therefore, as this patient continued to identify as female and desired further female phenotypic features, she was started on leuprolide to suppress further virilization, estrogen for feminization, and specifically referred to a DSD counsellor prior to finalizing a surgical decision. Given her age, the ethics committee was consulted prior to offering surgical interventions.

Comments: The deficiency of 17β-HSD3 is a rare cause of 46XY DSD, which can be screened by assessment of the androstenedione-to-testosterone ratio in cases with ambiguous genitalia or pubertal delay followed by confirmation of diagnosis with genetic testing. Early diagnosis and psychosocial management of such patients along with medical management is essential. Multidisciplinary care by Pediatric Endocrinology, Gynecology, and Psychology played an essential role in aligning patient gender identity, hormonal therapy management, and crucial emotional support through the course of her care.