Panayiotopoulos Aristotle, Bhangoo Amrit, Khurana Divya, Ten Svetlana, Michl Josef, Ghanny Steven
Pediatric Endocrinology, Staten Island University Hospital, Staten Island, New York.
Pediatric Endocrinology, CHOC Children's' Hospital, Orange, California.
J Endocr Soc. 2020 Aug 4;4(9):bvaa111. doi: 10.1210/jendso/bvaa111. eCollection 2020 Sep 1.
We hypothesize that impaired glucocorticoid sensitivity (GC sensitivity) plays a role in the development of premature adrenarche (PA) and polycystic ovarian syndrome (PCOS) by increasing androgen synthesis.
To study glucocorticoid sensitivity in vitro in subjects with PA and PCOS.
Fourteen subjects (10 girls, 4 boys, 6.9 ± 0.6 years) with PA; 27 subjects with PCOS (17 ± 2.5 years) and 31 healthy controls were enrolled in the study. All subjects and controls underwent GC sensitivity analysis in vitro using a fluorescein labeled-dexamethasone (F-DEX) assay. A GC sensitivity index (GCSI) was calculated as area under the curve of the F-DEX assay results. Subjects were classified as GC resistant if the GCSI ≤ 264 and GC sensitive if the GCSI ≥ 386.
In the PA group, 8 of 14 subjects were resistant with GCSI of 179.7 ± 39.9, 4 were within the normal range with GCSI of 299.6 ± 27.9, and 2 had increased GC sensitivity with GCSI of 423.5 ± 47.9. In the PCOS group, 18 of 27 subjects were GC-resistant with GCSI of 180.9 ± 58.2, 8 were within the normal range with GCSI of 310.7 ± 26.4, and 1 had increased GCSI of 395.4. In the PCOS GC-resistant subgroup, cortisol was higher compared with PCOS with normal GCSI ( < 0.05). In the combined PCOS plus female control group, GCSI correlated negatively with cortisol and testosterone ( < 0.05).
GC resistance was found in more than 50% of patients with PCOS and PA. The findings strongly suggest that GC resistance is associated with states of PA and PCOS.
我们假设糖皮质激素敏感性受损（GC敏感性）通过增加雄激素合成在青春期早熟（PA）和多囊卵巢综合征（PCOS）的发生发展中起作用。
研究PA和PCOS患者的体外糖皮质激素敏感性。
本研究纳入了14例PA患者（10名女孩，4名男孩，6.9±0.6岁）；27例PCOS患者（17±2.5岁）和31名健康对照者。所有受试者和对照者均采用荧光素标记地塞米松（F-DEX）检测法进行体外GC敏感性分析。计算GC敏感性指数（GCSI），即F-DEX检测结果曲线下面积。若GCSI≤264，则受试者被分类为GC抵抗；若GCSI≥386，则受试者被分类为GC敏感。
在PA组中，14例受试者中有8例抵抗，GCSI为179.7±39.9；4例在正常范围内，GCSI为299.6±27.9；2例GC敏感性增加，GCSI为423.5±47.9。在PCOS组中，27例受试者中有18例GC抵抗，GCSI为180.9±58.2；8例在正常范围内，GCSI为310.7±26.4；1例GCSI增加，为395.4。在PCOS的GC抵抗亚组中，与GCSI正常的PCOS患者相比，皮质醇水平更高（P<0.05）。在PCOS加女性对照组中，GCSI与皮质醇和睾酮呈负相关（P<0.05）。
超过50%的PCOS和PA患者存在GC抵抗。这些发现强烈提示GC抵抗与PA和PCOS状态相关。
