Endocrine Abstracts

Backgound: We report a case of a 63-year-old postmenopausal female diagnosed with ovarian hyperthecosis masked by concurrent use of an aromatase inhibitor.

Following diagnosis of breast cancer in 2009, requiring mastectomy with adjunctive chemotherapy, she was commenced on anastrozole. Later she noted gradual onset of frontal balding and hirsutism. Biochemistry revealed elevated serum levels of testosterone 13.2 nmol/l (range: <1.9 nmol/l) and androstenedione 25.6 nmol/l (range: 1.0–8.5 nmol/l) with normal DHEA levels. Raised androgen levels were presumed to be a consequence of concurrent use of anastrazole, an aromatase inhibitor. Despite switching to tamoxifen her testosterone levels continued to rise (13.8 nmol). MRI pelvis showed a right adnexal mass without any hallmark diagnostic features. Selective venous catheterisation of ovarian veins confirmed a right to left androgen gradient. Histology following bilateral salpingo-oophorectomy showed focal mild stromal hyperplasia with hyperthecosis. Subsequently both testosterone and androstenedione returned within normal limits.

Discussion: Ovarian hyperthecosis underpins an abnormal production of androgens from luteinized theca cells within the ovary. Primarily in postmenopausal women, it is characterised by severe hyperandrogenism and insulin resistance. Patients present with slowly, progressive hirsutism and virilization with raised testosterone levels. Although elevated testosterone levels with hyperthecosis on imaging confirm diagnosis, additional investigations including ovarian venous sampling and GnRH agonist testing may be required. Treatment of hyperthecosis depends on age, degree of virilisation, and pregnancy goals. In postmenopausal women and premenopausal women not planning future pregnancies, treatment options are bilateral oophorectomy or long-term GnRH-agonist treatment. In premenopausal women, symptomatic treatment of hirsutism and ovulation induction for infertility may be indicated.

Summary: Ovarian hyperthecosis should be considered in post-menopausal women with hyperandrogenism. Furthermore, with concurrent use of aromatase inhibitors, it should be considered as a differential if testosterone levels fail to decline following discontinuation of potential incriminating drug.