Ashley B. Humrickhouse: No financial relationships to disclose
Title Negative Imaging Does Not Exclude Ovarian Androgen-Secreting Tumors in Severe Postmenopausal Hyperandrogenism
Introduction Virilizing ovarian tumors are rare, accounting for < 1% of ovarian tumors and < 0.2% of hyperandrogenism cases in women. In postmenopausal patients, rapid-onset virilization with testosterone levels >150–200 ng/dL is highly suggestive of an androgen-secreting neoplasm, even when initial imaging is unrevealing. Up to 25% of ovarian androgen-producing tumors are not visualized on CT or ultrasound. This case highlights the limitations of initial imaging and reinforces that surgery is indicated based on biochemical severity alone, with imaging serving as an adjunct, not a prerequisite, for diagnosis.
Case A 77-year-old woman presented with one year of progressive virilization (deepening voice, clitoromegaly, hirsutism, alopecia). She had no exogenous hormone exposure. Laboratory evaluation revealed markedly elevated total testosterone measured by LC–MS/MS at 873 ng/dL (reference 7–40 ng/dL), increasing to 936.9 ng/dL on repeat testing. DHEA-S was normal at 71.3 µg/dL (13.9–142.8 µg/dL), and cortisol appropriately suppressed following a 1-mg overnight dexamethasone suppression test (1.1 µg/dL). Androstenedione was elevated at 149 ng/dL (17–99 ng/dL). This was supportive of a non-adrenal source of androgen excess. CT of the abdomen and pelvis with and without contrast showed no adrenal or ovarian mass. Despite the negative imaging, the severity of virilization and degree of testosterone elevation were strongly suggestive of an ovarian source. Pelvic MRI subsequently identified a subtle 1.7-cm right ovarian lesion. The patient underwent total robotic hysterectomy with bilateral salpingo-oophorectomy. Pathology confirmed a benign Leydig cell tumor. Postoperatively, testosterone and androstenedione normalized (18.7 ng/dL and 44 ng/dL), with resolution of virilization.
Discussion Biochemical severity should guide management. In postmenopausal women, testosterone levels >150–200 ng/dL are highly suggestive of an androgen-secreting neoplasm, regardless of whether CT or ultrasound identifies a lesion. Ovarian Leydig and Sertoli–Leydig cell tumors are frequently < 2 cm and may be occult on cross-sectional imaging. Although MRI offers superior soft-tissue resolution and may identify small stromal tumors, definitive surgical management should not be delayed when clinical and biochemical suspicion is high. Multiple reports describe successful surgical intervention despite negative imaging, with pathology subsequently confirming small ovarian neoplasms.
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