Diagnostic thresholds for androgen-producing tumors or pathologic hyperandrogenism in women by use of total testosterone concentrations measured by liquid chromatography-tandem mass spectrometry

BACKGROUND: Previously defined thresholds for total testosterone (TT) concentrations to screen for androgenproducing tumors (APTs) have used RIA, which can be less accurate in women. We aimed to define diagnostic thresholds to screen for APTs or postmenopausal pathologic hyperandrogenism using TT concentrations measured by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). METHODS: We performed a retrospective cohort study on all women with TT > 3.5 nmol/L and all postmenopausal women presenting with hyperandrogenism between 2004 and 2014 at the Mayo Clinic in Rochester, MN. RESULTS: Of the 369 women with TT > 3.5 nmol/L, 89 were included and subdivided into 3 groups based on their clinical diagnosis [21 (24%), APT; 16 (18%), postmenopausal pathologic hyperandrogenism; 52 (58%), polycystic ovary syndrome]. The source of the APT was more frequently ovarian (81%, n = 17) than adrenal (19%, n4). The diagnostic threshold usingROCanalysis for TT to identify APT in women with severe biochemical hyperandrogenemia was =5.1 nmol/L (sensitivity, 90%; specificity, 81%). In a second analysis of a cohort of postmenopausal women only presenting with symptoms or signs of hyperandrogenism, median TT was significantly higher in the postmenopausal pathologic hyperandrogenism group (APT and ovarian hyperthecosis) vs the idiopathic hyperandrogenism group (4.9 vs 0.8 nmol/L; P < 0.01). In postmenopausal women, the diagnostic threshold for pathologic hyperandrogenism was TT >2.2 nmol/L (sensitivity, 100%; specificity, 86%). CONCLUSIONS: The diagnostic threshold for TT concentration as measured by LC-MS/MS to identify APT in women with biochemical severe hyperandrogenemia was TT > 5.1 nmol/L. In postmenopausal women, the diagnostic threshold for pathologic hyperandrogenism was lower (TT > 2.2 nmol/L).