A case of postmenopausal ovarian hyperandrogenism of uncertain etiology

Introduction New onset hyperandrogenism in postmenopausal female is a rare occurrence, presenting with hirsutism or signs and symptoms of virilization. The causes of hyperandrogenism in postmenopausal female can be categorized into tumorous (androgen-secreting ovarian or adrenal tumors) and non-tumorous in origin (Hyperthecosis, Cushing’s syndrome, Acromegaly, Congenital Adrenal Hyperplasia, and iatrogenic). Here we present a case of severe hyperandrogenism of ovarian origin in a postmenopausal female where definite etiology could not be ascertained either by imaging or pathology. Case A 72-year-old female was referred to endocrinology clinic for complaints of worsening alopecia and hirsutism for the past 4 years. History was positive for weight gain of 80 lbs in the last ten years, menstrual irregularities since menarche, and recent deepening of voice. She denied exposure to exogenous androgenic steroid. Physical examination was remarkable for android obesity, severe male pattern alopecia, hirsutism involving face and deepening of voice, no clitoromegaly was noted. Lab evaluation showed elevated total testosterone level 261 ng/dl (normal value: 2-45 ng/dL) and free testosterone 14.1 pg/mL (normal value: 0.2-3.7 pg/mL ). Estradiol level was elevated and FSH and LH were low for a post-menopausal state. 17 hydroxy progesterone, TSH, and 1 mg overnight dexamethasone suppression test were normal ruling out congenital adrenal hyperplasia, thyroid dysfunction and Cushing’s syndrome. IGF-1 was not elevated ruling out acromegaly. DHEAS level was normal and CT abdomen and pelvis showed no evidence of an adrenal tumor, excluding adrenal source of androgen excess. Transvaginal Ultrasound showed normal volume of the ovaries, thickened endometrium and uterine myomas. Given markedly elevated testosterone levels and exclusion of adrenal tumor, suspicion for an ovarian source remained high. An MRI of the pelvis was done that showed 1.9 cm left adnexal cyst. She was then referred to Gynecology and underwent total hysterectomy with bilateral salpingo-oophorectomy. Interestingly surgical pathology was negative for tumor, showed unremarkable ovaries and right fallopian tube, left fallopian tube with hydrosalpinx, and showed atypical hyperplasia of the endometrium. However, testosterone levels decreased to normal two months after surgery; Free testosterone 1.8 pg/ml (normal values: 0.2-3.7 pg/mL), total testosterone 31 ng/dl (normal value: 2-45 ng/dL) indicating removal of ovarian source of testosterone production. Discussion Although relatively rare, severe hyperandrogenism (total testosterone \u3e150 ng/dL, DHEAS \u3e700 mcg/dL, signs of virilization) in postmenopausal women is caused either by adrenal or ovarian androgen secreting tumor or ovarian hyperthecosis, which is characterized by a hyperplastic ovarian stroma. Severity of symptoms, degree of androgen excess followed by imaging studies lead to identification of source of excessive androgen secretion in most cases. Diagnosis of ovarian virilizing tumors can be difficult since size of such tumors is often too small to allow detection on imaging studies, but are generally detected on surgical pathology and therefore bilateral salpingo-oophorectomy is recommended after exclusion of adrenal cause. However, rarely etiology may remain undetermined in some cases with conventional histology as in our patient