(7) A Unique Presentation of Primary Amenorrhea: Bilateral Ovarian Hyperthecosis in an Adolescent with Bardet-Biedl Syndrome

Background: Ovarian hyperthecosis (OH) is a cause of hyperandrogenism (HA) primarily occurring in postmenopausal women; extensive literature review shows no cases of OH occurring in a premenarchal patient. Bardet-Biedel Syndrome (BBS) is a genetic disorder associated with a constellation of symptoms including obesity and metabolic disorders; there has been one other documented case of BBS associated with OH occurring in a 40-year-old. We present a case of OH causing primary amenorrhea and virilization in a teen with BBS.

Case: IRB exempt status was confirmed through our IRB process. A 15-year-old female with history of BBS presented with primary amenorrhea and HA. Exam notable for Tanner stage IV breast development, clitoromegaly, moderate acne, and hirsutism. Laboratory workup notable for significantly elevated total testosterone (TT) of 394, confirmed on repeat. No identifiable source of exogenous testosterone. Imaging studies with normal post-pubertal uterus; negative for ovarian or adrenal masses. Congenital adrenal hyperplasia and genetic testing were normal. Negative progestin challenge. Gonadal vein sampling performed, with right ovarian vein TT 4780 and all other sites TT 500-600, raising suspicion for unilateral OH. Due to medical co-morbidities, most medication options were contraindicated. Patient underwent laparoscopic right oophorectomy; OH confirmed on pathology. Following oophorectomy, TT levels initially dropped but then rose again and remained persistently elevated over 1 year. After extensive counseling and shared decision-making with the patient and family, decision was made to proceed with left oophorectomy, and pathology confirmed OH of the left ovary. IUD was placed during surgery for endometrial protection; she was started on estradiol patches for hormone replacement. FT and TT down trended to normal levels, and hirsutism and acne improved; she also reported significant improvement in her mood. Monitoring of TT levels is ongoing.

Comments: Identifying the etiology for HA in young patients can be difficult; PCOS is often used as a catch-all diagnosis, especially in the setting of obesity and other metabolic disorders. Our case highlights a rare cause of HA, which easily could have been mistaken for severe PCOS; in addition, treatment was particularly difficult given her co-morbidities which precluded most medication management options. We hope this case can offer an example of extended work up of HA, especially when lab values and clinical manifestations do not align, as well as one management option in a medically complex patient when standard guidelines cannot be followed.