Swart Amanda C, du Toit Therina, Gourgari Evgenia, Kidd Martin, Keil Meg, Faucz Fabio R, Stratakis Constantine A
Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa.
Section on Genetics and Endocrinology (SEGEN), Intramural Research Program (IRP), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD, USA.
Pediatr Res. 2021 Jan;89(1):118-126. doi: 10.1038/s41390-020-0870-1. Epub 2020 Apr 4.
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-MS/MS). We hypothesized that UPC-MS/MS may be used to better define hormonally this distinct subgroup of patients with PCOS.
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-MS/MS analysis. When insufficient, samples were pooled from patients with similar responses to allow quantification over the low end of the assay.
The C11-oxy C (11β-hydroxyandrostenedione, 11keto-androstenedione, 11β-hydroxytestosterone, 11keto-testosterone):C (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 steroids, 11-hydroxyprogesterone and 11keto-dihydroprogesterone levels, were 1.2- and 1.7-fold higher in PCOS patients compared to HVs, respectively.
We hypothesized that UPC-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.
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.
我们最近鉴定出35例患有多囊卵巢综合征（PCOS）且表现出微结节性肾上腺皮质增生特征的女性。使用最先进的超高效合相色谱 - 串联质谱法（UPC-MS/MS）进行类固醇激素分析可能会更准确。我们推测UPC-MS/MS可用于更好地从激素水平上界定这一独特的PCOS患者亚组。
对接受地塞米松检测的PCOS患者（n = 35）和健康志愿者（HV，n = 19）的血浆进行分析。样本根据地塞米松反应分组，然后进行UPC-MS/MS分析。如果样本量不足，则将反应相似的患者样本合并，以便在检测下限进行定量分析。
与健康志愿者相比，PCOS患者的C11-氧代C（11β-羟基雄烯二酮、11-酮基雄烯二酮、11β-羟基睾酮、11-酮基睾酮）：C（雄烯二酮、睾酮）类固醇比值降低了1.75倍。下游类固醇代谢物11β-羟基雄甾酮和11-酮基雄甾酮也可检测到。与健康志愿者相比，PCOS患者的C11-氧代C类固醇、11-羟基孕酮和11-酮基二氢孕酮水平分别高出1.2倍和1.7倍。
我们推测UPC-MS/MS可以在体内准确地定量类固醇，并识别PCOS和肾上腺异常患者亚组中的新型代谢物。事实上，肾上腺C11-氧代类固醇有可能用于诊断，以识别患有PCOS且有微结节性肾上腺皮质增生证据的年轻女性和青少年。
肾上腺C11-氧代类固醇在识别患有PCOS和肾上腺异常的年轻患者方面可能具有临床重要性。我们论文中提出的类固醇在临床环境中迄今尚未被考虑，我们认为这项研究可能是朝着表征一个独特的PCOS女性亚组迈出的第一步，该亚组患者实际上可能与普通PCOS患者的治疗方式不同。本文可以改变对PCOS作为一种单一疾病的理解：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，本文还增加了对患有PCOS的年轻女性和青春期女孩类固醇生成过程中肾上腺 - 卵巢相互作用的基本病理生理学理解。
