BACKGROUND We recently identified 35 women with polycystic ovarian syndrome (PCOS) who 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 (HVs, n = 19) who all received dexamethasone testing was analyzed. Samples were grouped per dexamethasone responses and followed by UPC 2 -MS/MS analysis. 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 patients compared to HVs. Downstream steroid metabolites 11β-hydroxyandrosterone and 11keto-androsterone 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 patients compared to HVs, 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 and 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. Impact Adrenal C11-oxy steroids may be clinically important in identifying young patients with PCOS and adrenal abnormalities. The steroids presented in our manuscript have not yet been considered in the clinical setting so far, and we believe that this study could represent a first focused step towards the characterization of a distinct subgroup of women with PCOS who may in fact be treated differently than the average patient with PCOS. This paper can change the understanding of PCOS as one disorder: it is in fact a heterogeneous condition. In addition, for the subgroup of patients with PCOS associated with adrenocortical dysfunction, our paper provides novel hormonal markers that can be used diagnostically. Finally, the paper also adds to the basic pathophysiological understanding of adrenocortical-ovarian interactions in steroidogenesis of young women and adolescent girls with PCOS.

中文翻译：

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使用 UPC2-MS/MS 分析患有多囊卵巢综合征和肾上腺皮质功能障碍的青少年和年轻女性的类固醇激素

背景 我们最近确定了 35 名患有多囊卵巢综合征 (PCOS) 的女性，她们表现出微结节性肾上腺皮质增生的特征。使用最先进的超高效会聚色谱-串联质谱 (UPC 2 -MS/MS) 可以更准确地分析类固醇激素。我们假设 UPC 2 -MS/MS 可用于更好地定义这一独特的 PCOS 患者亚组的激素水平。方法 分析了所有接受地塞米松检测的 PCOS 患者（n = 35）和健康志愿者（HV，n = 19）的血浆。样品按地塞米松反应分组，然后进行 UPC 2 -MS/MS 分析。当不足时，从具有相似反应的患者中收集样本，以允许在检测的低端进行量化。结果 C11-oxy C 19（11β-羟基雄烯二酮、11酮-雄烯二酮、与 HV 相比，PCOS 患者的 11β-羟基睾酮、11 酮-睾酮）：C 19（雄烯二酮、睾酮）类固醇比率降低了 1.75 倍。下游类固醇代谢物 11β-羟基雄酮和 11 酮-雄酮也是可测量的。与 HV 相比，PCOS 患者的 C11-oxy C 21 类固醇、11-羟基孕酮和 11-酮-二氢孕酮水平分别高 1.2 倍和 1.7 倍。结论 我们假设 UPC 2 -MS/MS 可以在体内准确量化类固醇，并在患有 PCOS 和肾上腺异常的患者亚组中鉴定新的代谢物。事实上，似乎肾上腺 C11-氧基类固醇有可能被用于诊断患有 PCOS 的年轻女性和青少年，这些女性和青少年也有一些微结节性肾上腺皮质增生的证据。影响 肾上腺 C11-氧基类固醇在识别患有 PCOS 和肾上腺异常的年轻患者方面可能具有重要的临床意义。到目前为止，我们手稿中的类固醇尚未在临床环境中考虑过，我们认为，这项研究可能代表着对多囊卵巢综合征女性的不同亚组进行表征的第一个重点步骤，这些女性实际上可能会受到不同的治疗普通多囊卵巢综合征患者。这篇论文可以改变对 PCOS 是一种疾病的理解：它实际上是一种异质性疾病。此外，对于与肾上腺皮质功能障碍相关的 PCOS 患者亚组，我们的论文提供了可用于诊断的新型激素标志物。最后，