ECEESPE2025 Poster Presentations Adrenal and Cardiovascular Endocrinology (169 abstracts)
Cortisol secretion and its tissue sensitivity are associated with the comorbidities of obese patients without Cushing Syndrome
Ilinka Garavaglia 1 , Ilaria Gentile 1 , Alessandro Amodeo 1 , Nicoletta Del Duca 2 , Gabriele Pogliaghi 1 , Alessandra Milesi 3 , Stefania Mai 4 , Alice Casiraghi 1 , Davide Soranna 5 , Antonella Zambon 6,7 , Valentina Morelli 8 , Marco Bonomi 9,10 , Massimo Scacchi 2,11 , Luca Persani 12,13 & Biagio Cangiano 1,12
1Department of Medical Biotechnology and Translational Medicine, Milan, Italy; 2Istituto Auxologico Italiano, IRCCS, Division of General Medicine, Ospedale S. Giuseppe, Oggebbio-Piancavallo, Verbania, Italy; 3Laboratory of Metabolic Research, IRCCS Istituto Auxologico Italiano, San Giuseppe Hospital, Piancavallo, Verbania, Italy; 4Laboratory of Metabolic Research, IRCCS Istituto Auxologico Italiano, San Giuseppe Hospital, Verbania, Italy; 5Istituto Auxologico Italiano, IRCCS, Biostatistics Unit, Milan, Italy; 6Division of Biostatistics, Epidemiology and Public Health, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy; 7IRCCS, Istituto Auxologic Italiano, Biostatistics Unit, Milan, Italy; 8UOSD Bone Metabolic Diseases and Diabetes, Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy; 9Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy; 10Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy; 11Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; 12Division of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy; 13Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
JOINT3558
Background: The tissue ‘milieu’ of cortisol, intended as cortisol secretion combined with its tissue sensitivity could have an impact on obesity and its comorbidities such as type 2 diabetes mellitus (T2DM), arterial hypertension (AH), depressive syndrome (DS) and cardiovascular disease (CVD), in subjects without Cushing Syndrome.
Objective: This study aimed at evaluating cortisol secretion together with glucocorticoids (GCs) receptor sensitivity through the determination of glucocorticoid receptor polymorphisms (GRp) in severely obese subjects, exploring their association with obesity’s degree and comorbidities.
Methods: A total of 193 male subjects (age>18) suffering from severe obesity (BMI>35 kg/m2) were consecutively enrolled in a cross-sectional observational study. For each patient we collected clinical history and presentation and performed blood tests for metabolic and gonadal function. We evaluated night-time cortisol blood levels and the morning cortisol after 1 mg of dexamethasone overnight suppresion test (OST); GRp (BclI, rs41423247; N363S, rs56149945 increasing the sensitivity and ER22/23EK, rs6189+ rs6190 reducing it) were evaluated using restriction enzymes. Both logistic regression analyses and a machine learning naive approach were used to explore the association of cortisol milieu with AH, T2DM, DS and CVD. Polysomnography was used to determine if decompensated obstructive sleep apneas were present, to adjust the analyses together with age, BMI and smoking habit (pack-years).
Results: In our cohort 74% of patients exhibited AH, 42% had T2DM, and 37% experienced varying degrees of DS according to the Beck Depression Inventory; the 17% had a history of CVD. At multivariate analyses cortisol levels after OST were associated with the presence of T2DM (P=0.007) and diabetic nephropathy (P=0.025), whereas GRp increasing sensitivity to cortisol were independently associated with AH (P=0.04) and CVD (P=0.03). Depression, did not show any significant correlation. Using ‘Random Forest’ machine learning analyses we found that the addition of GRp and hypogonadotropic hypogonadism to the known factors (such as hypertension, renal function, HOMA index, BMI and age) increased the prediction performance of CVD in obese patients.
Conclusions: The combined study of cortisol secretion and peripheral sensitivity to GCs in the absence of overt hypercortisolism seems to provide additional information on the mechanisms leading to the development of obesity comorbidities, both using classic statistical methods and machine learning naive approaches. If confirmed, this could have potential use in identifying subjects deserving specific treatments aimed at modulating GCs action.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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