Pelvic ultrasonography was suspicious for an ovarian pathology. Follow-up pelvic magnetic resonance imaging (MRI) demonstrated a 2.5-cm mass abutting the left ovary (Figure 2). The patient was given a diagnosis of stage IIIA high-grade ovarian serous carcinoma with lymph node involvement. Other notable findings from the workup included a BRCA2 mutation and concurrent renal cell carcinoma. After bilateral salpingo-oophorectomy, partial nephrectomy, and chemotherapy with carboplatin and paclitaxel, the testosterone level returned to within reference range and remained stable for the next 2 years of follow-up.
Figure 2. A and B, Axial T1–weighted and sagittal T2–weighted pelvic magnetic resonance imaging, respectively, demonstrated a 2.5-cm mass (red arrows) abutting the left ovary.
Female pattern hair loss is common in postmenopausal women and is a frequent concern in patients presenting to dermatology. Although most cases of androgenetic alopecia are isolated or secondary to benign conditions, such as polycystic ovary syndrome or nonclassic congenital adrenal hyperplasia, a small minority(<1% of women presenting with signs of hyperandrogenism) have an androgen-secreting tumor.6
Rapid onset or worsening of clinical hyperandrogenism, as seen in our patient, should raise concern for pathology; serum total testosterone and DHEA-S levels should be evaluated. Abnormally elevated serum androgens are associated with malignancy; however, there is variability in the recommended cutoff levels to prompt suspicion for an androgen-producing tumor and further workup in postmenopausal women.7 In the case of testosterone elevation, classic teaching designates a testosterone level greater than 200 ng/dL as the appropriate threshold for concern, but this level is now debated. In a series of women with hyperandrogenism referred to a center for suspicion of an androgen-secreting tumor, those with a tumor had, on average, a significantly higher (260 ng/dL) testosterone level than women who had other causes (90 ng/dL)(P<.05).6 The authors of that study proposed a cutoff of 1.4 ng/mL because women in their series who had a tumor were 8.4 times more likely to have a testosterone level of 1.4 ng/mL or higher than women without a tumor. However, this cutoff was only 92% sensitive and 70% specific.6 The degree of androgen elevation is highly variable in both tumorous and benign pathologies with notable overlap, challenging the notion of a clear cutoff.
Imaging is indicated for a patient presenting with both clinical and biochemical hyperandrogenism. Patients with an isolated testosterone level elevation can be evaluated with transvaginal ultrasonography; however, detection and characterization of malignancies is highly dependent on the skill of the examiner.8,9 The higher sensitivity and specificity of pelvic MRI reduces the likelihood of missing a malignancy and unnecessary surgery. Tumors too small to be visualized by MRI rarely are malignant.10
Sex cord-stromal cell tumors, despite representing fewer than 10% of ovarian tumors, are responsible for the majority of androgen-secreting malignancies. Our patient presented with clinical hyperandrogenism with an elevated testosterone level in the setting of a serous ovarian carcinoma, which is an epithelial neoplasm. Epithelial tumors are the most common type of ovarian tumor and typically are nonfunctional, though they have been reported to cause hyperandrogenism through indirect mechanisms. It is thought that both benign and malignant epithelial tumors can induce stromal hyperplasia or luteinization, leading to an increase in androgen levels.6
Due to the high prevalence of androgenetic alopecia and hirsutism in aging women, identification of androgen-secreting neoplasms by clinical presentation is challenging. A wide range of serum testosterone levels is possible at presentation, which complicates diagnosis. This case highlights the importance of correlating clinical and biochemical hyperandrogenism in raising suspicion of malignancy in older women presenting with hair loss.