Valentina Morelli1, Carmen Aresta2,3, Agostino Gaudio4, Cristina Eller-Vainicher1, Volha V Zhukouskaya5, Daniela Merlotti6, Emanuela Orsi4, Anna Maria Barbieri1,3, Silvia Fustinoni3,7, Elisa Polledri3,7, Luigi Gennari6, Alberto Falchetti2, Vincenzo Carnevale8, Luca Persani2,3, Alfredo Scillitani9, Iacopo Chiodini10,11. 1. Unit of Endocrinology, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milan, Italy. 2. Unit for Bone Metabolism Diseases and Diabetes & Lab of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy. 3. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. 4. Department of Clinical and Experimental Medicine, University of Catania, University Hospital 'G. Rodolico', Catania, Italy. 5. Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy. 6. Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy. 7. Unit of Epidemiology, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milan, Italy. 8. Unit of Internal Medicine, Ospedale "Casa Sollievo della soffererenza" IRCCS, San Giovanni Rotondo, FG, Italy. 9. Endocrinology and Diabetology, Ospedale "Casa Sollievo della soffererenza" IRCCS, San Giovanni Rotondo, FG, Italy. 10. Unit for Bone Metabolism Diseases and Diabetes & Lab of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy. iacopo.chiodini@unimi.it. 11. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. iacopo.chiodini@unimi.it.
Abstract
PURPOSE: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
Authors: M P de Paula; A B Moraes; M das Graças Coelho de Souza; E M R Cavalari; R C Campbell; G da Silva Fernandes; M L F Farias; L M C Mendonça; M Madeira; E Bouskela; L G Kraemer-Aguiar; L Vieira Neto Journal: J Endocrinol Invest Date: 2020-07-19 Impact factor: 4.256