Endocrine Abstracts

Introduction

Severe hyperandrogenism is a warning sign in young women. Differential diagnosis includes neoplastic, non-neoplastic and iatrogenic causes. The association of hyperandrogenism and congenital or acquired portosystemic shunt (PSS) has been rarely described, with its pathophysiology being unclear.

Case 1

A 22 year-old woman with diagnosis of autoimmune hepatitis, portal hypertension and PSS since 15 years old, presented with a 4 years history of oligomenorrhea and hirsutism [Ferriman-Gallwey (FG) score 12]. Examination revealed BMI 30.7 Kg/m² and virilization signs. Total testosterone (TT) was 3.60 ng/ml (0.1–0.56) and androstenedione 12.4 ng/ml (0.5–4.7). 17OHP, S-DHEA and SHBG were normal. Serum glucose 83 mg/dl, insulin 20 uUI/ml (1.9–23), HOMA-IR 0.7. CT scan excluded adrenal lesions. Ultrasound showed “ovaries with 56 and 58 mm and multiple peripheral follicles”. In view of the severe hyperandrogenism of probable ovarian etiology, catheterization of the ovarian veins was performed, excluding ovarian lateralization or central/peripheral gradient of androgen levels. The patient completed 17 months of goserrelin acetate with slight improvement in hyperandrogenism (TT 1.88 ng/ml, androstenedione 8.58 ng/ml). Due to poor therapeutic adherence and necessary contraception, an ethonogestrel implant was applied.

Case 2

A 18 year old woman, with portal hypertension due to portal vein agenesis diagnosed at 4 years old, presented with menstrual irregularities and hirsutism (FG score 10) since menarche at 14. She had a BMI 28.9 Kg/m² and no signs of virilization. TT was 2.12 ng/ml and androstenedione 5.27 ng/ml. 17OHP, S-DHEA and SHBG were normal. Serum glucose was 71 mg/dl and insulin 12.57 uUi/ml, HOMA-IR 2.2. On ultrasound, “right ovary (30.4 × 26.4 mm) with functional cyst and multifollicular left ovary (31.4 x16 mm)” stood out. Abdominal-pelvic MRI confirmed portal vein agenesis and excluded ovarian and adrenal lesions. In view of the mild clinical symptoms and the need for contraception, a levonorgestrel IUD was inserted.

Conclusion

PSS can cause hyperinsulinemia by direct passage of secreted insulin to the systemic circulation and consequent insulin resistance by downregulation mechanisms. This is a possible explanation for the hyperandrogenism associated with PSS, similarly to what happens in polycystic ovary syndrome. Decreased hepatic clearance of androgens, in particular testosterone, may be an additional factor. Treatment depends on age, degree of virilization and pregnancy goal which justified the different approach in these patients.