Steroid hormone analysis of adolescents and young women with polycystic ovarian syndrome and adrenocortical dysfunction using UPC(2) -MS/MS

BACKGROUND: We recently identified 35 women with PCOS that exhibited features of micronodular adrenocortical hyperplasia. Steroid hormone analysis can be more accurate using state-of-the-art ultra-performance-convergence-chromatography-tandem-mass-spectrometry (UPC(2)-MS/MS). We hypothesized that UPC(2)-MS/MS may be used to better define hormonally this distinct subgroup of patients with PCOS. METHODS: Plasma from PCOS patients (n=35) and healthy volunteers (HV, n=19) who all received dexamethasone testing was analyzed. Samples were grouped per dexamethasone responses and UPC(2)-MS/MS analysis followed. When insufficient, samples were pooled from patients with similar responses to allow quantification over the low end of the assay. RESULTS: The C11-oxy C(19) (11β-hydroxyandrostenedione, 11keto-androstenedione, 11β-hydroxytestosterone, 11keto-testosterone): C(19) (androstenedione, testosterone) steroid ratio was decreased by 1.75-fold in PCOS compared to HV. Downstream steroid metabolites 11β-hydroxyandrosterone and 11keto-androsterone metabolites were also measurable. The C11-oxy C(21) steroids, 11-hydroxyprogesterone and 11keto-dihydroprogesterone levels were 1.2- and 1.7-fold higher in PCOS compared to HV, respectively. CONCLUSIONS: We hypothesized that UPC(2)-MS/MS may accurately quantify steroids, in vivo, and identify novel metabolites in a subgroup of patients with PCOS with adrenal abnormalities. Indeed, it appears that adrenal C11-oxy steroids have the potential of being used diagnostically to identify younger women and adolescents with PCOS who also have some evidence of micronodular adrenocortical hyperplasia.