SFEBES2021 Early Careers and Plenary Orals Early Career Prize Lecture Basic Science (1) (1 abstracts)
Cardiometabolic disease burden and urine steroid metabolome in benign adrenocortical tumours: a case-control study
Alessandro Prete 1,2,3 , Anuradhaa Subramanian 4 , Irina Bancos 1,5 , Vasileios Chortis 12,3 , Stylianos Tsagarakis 6 , Katharina Lang 1,2,3 , Magdalena Macech 7 , Danae A Delivanis 5 , Ivana D Pupovac 8 , Giuseppe Reimondo 9 , Ljiljana V Marina 10 , Timo Deutschbein 11,12 , Maria Balomenaki 6 , Michael W O’Reilly 1,13 , Tomasz Bednarczuk 7 , Catherine Zhang 5 , Tina Dusek 8 , Aristidis Diamantopoulos 6 , Miriam Asia 2,3 , Agnieszka Kondracka 7 , Dingfeng Li 5 , Jimmy R Masjkur 14 , Marcus Quinkler 15 , Grethe Æ Ueland 16 , M Conall Dennedy 17 , Felix Beuschlein 18,19 , Antoine Tabarin 20 , Martin Fassnacht 11 , Miomira Ivovic 10 , Massimo Terzolo 9 , Darko Kastelan 8 , William F Young Jr 5 , Konstantinos N Manolopoulos 1 , Urszula Ambroziak 7 , Dimitra A Vassiliadi 6 , Angela E Taylor 1 , Alice J Sitch 4,21 , Krishnarajah Nirantharakumar 1,2,4 & Wiebke Arlt 1,2,3,21
1Institute of Metabolism and Systems Research, Birmingham, UK; 2Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK; 3Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. 4Institute of Applied Health Research, University of Birmingham, Birmingham, UK. 5Division of Endocrinology, Metabolism, Diabetes and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA. 6Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital, Athens, Greece. 7Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland. 8Department of Endocrinology, University Hospital Centre Zagreb, Zagreb, Croatia. 9Division of Internal Medicine, University of Turin, San Luigi Hospital, Turin, Italy. 10Department for Obesity, Reproductive and Metabolic Disorders, Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 11Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany. 12Medicover Oldenburg MVZ, Oldenburg, Germany. 13Department of Medicine, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland. 14Department of Medicine III and Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany. 15Endocrinology in Charlottenburg, Berlin, Germany. 16Department of Endocrinology, Haukeland University Hospital, Bergen, Norway. 17Department of Endocrinology, University Hospital Galway, Newcastle, Galway, Ireland. 18Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitäts-Spital Zürich (USZ) und Universität Zürich (UZH), Zurich, Switzerland. 19Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany. 20Service d’Endocrinologie, Centre Hospitalier Universitaire, Hopital du Haut Leveque, Pessac, France. 21NIHR Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Background: The overwhelming majority of incidentally discovered adrenal tumours are benign adrenocortical adenomas. These can be non-functioning (NFAT) or associated with cortisol excess on a spectrum ranging from rare clinically overt adrenal Cushing’s syndrome (CS) to much more prevalent mild autonomous cortisol secretion (MACS) without signs of CS. The 1mg-overnight dexamethasone suppression test (DST) further differentiates MACS-1 (possible MACS; post-DST cortisol 50–138 nmol/l) and MACS-2 (definitive MACS; post-DST cortisol >138 nmol/l). A recent systematic review and meta-analysis reported that benign adrenocortical tumours are associated with a high prevalence of metabolic disease; however, large-scale prospective data are lacking.
Methods: We analysed all patients with benign adrenocortical tumours and DST results recruited to the prospective ENSAT EURINE-ACT study (n=1305). The prevalence of hypertension, type 2 diabetes, and dyslipidaemia was compared to 5268 population controls from the 2014 cohort of the Health Survey for England using Poisson regression to obtain sex-, age- and BMI-adjusted prevalence ratios (aPR). In the patients, we also carried out multi-steroid profiling of 24-h urine by tandem mass spectrometry and compared results to 127 healthy controls using a sex-, age- and BMI-adjusted linear regression model.
Results: Cortisol excess was highly prevalent (MACS-1 34.6%, MACS-2 10.7%, CS 5%). Patients had higher rates of metabolic disease than population controls (hypertension: NFAT aPR 1.88 [95%CI 1.75–2.02], MACS-1 1.86 [1.74–1.99], MACS-2 2.08 [1.88–2.31], CS 2.97 [2.47-3.58]; type 2 diabetes: NFAT 4.11 [3.28–5.16], MACS-1 4.34 [3.47-5.44], MACS-2 5.30 [4.03–6.97], CS 10.17 [7.27–14.23]; dyslipidaemia: NFAT 1.76 [1.53–2.02], MACS-1 1.71 [1.49–1.97]), MACS-2 1.95 [1.52–2.50]; all P < 0.001). Urinary multi-steroid profiling revealed a gradual increase in glucocorticoid excretion from NFAT over MACS-1 and MACS-2 to CS while androgen excretion decreased.
Conclusion: Patients with benign adrenocortical tumours – including NFAT – have an increased cardiometabolic disease burden that increases with glucocorticoid output.
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Endocrine Abstracts
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