Ovarian Hyperthecosis: Hyperandrogenism in a Post-Menopausal Woman

Abstract

Introduction: Ovarian Hyperthecosis (OH) is a disorder characterized by severe hyperandrogenism and insulin resistance. It is a rare cause of hyperandrogenism primarily among postmenopausal women. We present a case report about a patient with adrenal incidentalomas and later found to have ovarian hyperthecosis during her evaluation. Case Description: 62-year-old post-menopausal female was referred to the Endocrinology clinic for evaluation of adrenal incidentalomas which were discovered on imaging work-up for hematuria. MRI Abdomen and Pelvis revealed a 17mm right and 14mm left sided adrenal nodules, with signal dropout suggesting benign adenomas. Patient stated she had menopause at age 39 years old, one child, and multiple miscarriages during her reproductive years. Examination revealed BMI of 31.1 kg/m2, moderate hirsutism, and skin tags near the neck. There was no evidence of hyperpigmentation or abdominal striae. Patient had phenotype suggestive of insulin resistance-without diagnosis of diabetes. Results: Laboratory workup revealed normal levels of 24-hour metanephrines, cortisol, renin, aldosterone, and DHEA-S suggesting that the adrenal adenomas were not hyperfunctioning. Further workup revealed: Total Testosterone: 220 [2 - 45 ng/dL]; Free Testosterone 23.8 [0.1 - 6.4 pg/mL]; DHEA-S 43 [12 - 133 mcg/dL]. Prolactin 6.3 [Postmenopausal 2.0-20.0 ng/mL]. A1c 5.4 [<5.7%]. Serum FSH, LH, PRL, and IGF-1 were within normal reference ranges. The patient, with adrenal adenomas, elevated testosterone, and a normal DHEA-S suggested a non-adrenal source. Patient was evaluated by OB/GYN with finding of normal postmenopausal ovaries on transvaginal ultrasonography. Based on a high suspicion for OH, patient underwent hysterectomy with bilateral salpingo-oophorectomy which confirmed pathological diagnosis of Bilateral OH. On follow-up 2 months post-op, Total/Free Testosterone had normalized 36 [2 - 45 ng/dL] and 3 [0.1 - 6.4 pg/mL] respectively). Conclusion: In women presenting with elevated testosterone (>150 ng/dL) and clinical features of hyperandrogenism, proper laboratory and imaging evaluation is imperative to determine the source of excess androgen production. Untreated, OH is associated with increased mortality from type 2 diabetes, cardiovascular disease, and endometrial carcinoma. The diagnosis of OH can be confirmed only by histologic examination of the ovaries. Often, ovarian imaging is negative, therefore, surgical intervention is recommended. Hence, clinicians should rely on the clinical assessment in making management decisions in patients with OH.