Morelli Valentina, Aresta Carmen, Gaudio Agostino, Eller-Vainicher Cristina, Zhukouskaya Volha V, Merlotti Daniela, Orsi Emanuela, Maria Barbieri Anna, Fustinoni Silvia, Polledri Elisa, Gennari Luigi, Falchetti Alberto, Carnevale Vincenzo, Persani Luca, Scillitani Alfredo, Chiodini Iacopo
Unit of Endocrinology, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milan, Italy.
Unit for Bone Metabolism Diseases and Diabetes & Lab of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy.
Endocrine. 2020 May;68(2):411-419. doi: 10.1007/s12020-020-02212-9. Epub 2020 Jan 27.
Cortisol secretion, peripheral activation, and sensitivity seem to be associated with hypertension (HY), type 2 diabetes (T2D), and fragility fractures (FX) even in eucortisolemic subjects. The aim of the present study was to determine the cutoff(s) of the parameters of cortisol secretion and peripheral activation for predicting the presence of HY, T2D, and FX (comorbidities).
In 206 postmenopausal females (157 with ≥1 comorbidities and 49 without any), we assessed the ratio between 24-h urinary free cortisol and cortisone (R-UFF/UFE, cortisol activation index), cortisol after 1 mg-overnight-dexamethasone (F-1mgDST, cortisol secretion index), and the GC receptor N363S single-nucleotide polymorphism (N363S-SNP, cortisol sensitivity index).
The cutoffs for F-1mgDST and R-UFF/UFE were set at 0.9 μg/dL (area under the curve, AUC 0.634 ± 0.43, p = 0.005) and 0.17 (AUC 0.624 ± 0.5, p = 0.017), respectively, predicted the presence of ≥1 comorbidities. The presence of F-1mgDST > 0.9 μg/dL plus R-UFF/UFE > 0.17 showed 82.1% specificity for predicting the presence of ≥1 comorbidities, while the simultaneous presence of F-1mgDST ≤ 0.9 μg/dL and R-UFF/UFE ≤ 0.17 showed 88% sensitivity for predicting the absence of comorbidities. The F-1mgDST > 0.9 μg/dL or R-UFF/UFE > 0.17 was associated with 2.8 and 2.1-fold increased risk of having ≥1 comorbidities, respectively. The F-1mgDST ≤ 0.9 μg/dL plus R-UFF/UFE ≤ 0.17 or F-1mgDST > 0.9 μg/dL plus R-UFF/UFE > 0.17 was associated with 2.8-fold reduced or 4.9-fold increased risk of having ≥1 comorbidities regardless of age, BMI, and N363S-SNP.
F-1mgDST > 0.9 μg/dL and R-UFF/UFE > 0.17 may be used for predicting the presence of ≥1 among HY, T2D, and fragility FX.
即使在皮质醇正常的受试者中，皮质醇分泌、外周激活和敏感性似乎也与高血压（HY）、2型糖尿病（T2D）和脆性骨折（FX）相关。本研究的目的是确定皮质醇分泌和外周激活参数的临界值，以预测HY、T2D和FX（合并症）的存在。
在206名绝经后女性中（157名有≥1种合并症，49名无任何合并症），我们评估了24小时尿游离皮质醇与可的松的比值（R-UFF/UFE，皮质醇激活指数）、1毫克过夜地塞米松后的皮质醇（F-1mgDST，皮质醇分泌指数）以及糖皮质激素受体N363S单核苷酸多态性（N363S-SNP，皮质醇敏感性指数）。
F-1mgDST和R-UFF/UFE的临界值分别设定为0.9μg/dL（曲线下面积，AUC 0.634±0.43，p=0.005）和0.17（AUC 0.624±0.5，p=0.017），可预测≥1种合并症的存在。F-1mgDST>0.9μg/dL加上R-UFF/UFE>0.17对预测≥1种合并症的存在具有82.1%的特异性，而F-1mgDST≤0.9μg/dL和R-UFF/UFE≤0.17同时存在对预测无合并症具有88%的敏感性。F-1mgDST>0.9μg/dL或R-UFF/UFE>0.17分别与发生≥1种合并症的风险增加2.8倍和2.1倍相关。无论年龄、体重指数和N363S-SNP如何，F-1mgDST≤0.9μg/dL加上R-UFF/UFE≤0.17或F-1mgDST>0.9μg/dL加上R-UFF/UFE>0.17分别与发生≥1种合并症的风险降低2.8倍或增加4.9倍相关。
F-1mgDST>0.9μg/dL和R-UFF/UFE>0.17可用于预测HY、T2D和脆性FX中≥1种合并症的存在。
