Severe Hyperandrogenism in A Premenopausal Woman With An Imaging-Negative Leydig Cell Tumor

ABSTRACT Objective Hirsutism and hyperandrogenism in premenopausal women are most often associated with polycystic ovarian syndrome. We present a case of progressive, severe hyperandrogenism with negative imaging identified on surgical histopathology as being due to a Leydig cell tumor (LCT), thus illustrating localization challenges associated with these small tumors. Methods Laboratory investigations included testosterone, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, 24-hour urine cortisol, and prolactin. Imaging included pelvic ultrasound, adrenal magnetic resonance imaging, and computed tomography. Ovarian vein sampling was not available. Results A 42-year-old woman presented with frontal alopecia, voice deepening, coarse facial hair, and amenorrhea on a background of lifelong oligomenorrhea. Peak testosterone was 30.2 nmol/L (female normal range is <2.0 nmol/L) with normal dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, prolactin, 24-hour urine cortisol, and thyroid-stimulating hormone. Transvaginal ultrasound, adrenal magnetic resonance imaging, and computed tomography of the thorax and abdomen revealed no androgen source. Testosterone failed to suppress with gonadotropin-releasing hormone agonist. Although no abnormality was seen during oophorectomy, surgical pathology documented a 1.8-cm, well-circumscribed hilar LCT. Postoperative testosterone was <0.5 nmol/L. Conclusion Although this patient had testosterone levels well into the masculine range, multiple imaging results were negative with a LCT found only after oophorectomy. LCTs are rare ovarian stromal tumors and while 50 to 70% of these tumors produce androgen, size and clinical severity may not be well correlated. This case report illustrates that despite an association with substantially elevated androgen levels, the small size of LCTs can result in localization challenges. Abbreviations FSH follicle-stimulating hormone GnRH gonadotropin-releasing hormone LCT Leydig cell tumor LH luteinizing hormone PCOS polycystic ovarian syndrome