Endocrine Abstracts (2019) 65 EC1.3 | DOI: 10.1530/endoabs.65.EC1.3

Urine steroid metabolome analysis allows for metabolic risk stratification in 1309 prospectively recruited patients with benign adrenal tumours and different degrees of cortisol excess

Alessandro Prete1,2, Angela E Taylor1, Alice J Sitch3, Lorna C Gilligan1, Dimitra Vassiliadi4, Urszula Ambroziak5, Katharina Lang1,2, Darko Kastelan6, Antoine Tabarin7, M Conall Dennedy8, Grethe Åstrøm Ueland9, Marcus Quinkler10, Jimmy Rusdian Masjkur11, Martin Fassnacht12, Miomira Ivovic13, Massimo Terzolo14, Felix Beuschlein15, Konstantinos Manolopoulos1,2, Michael W O’Reilly1,2, Stylianos Tsagarakis4, Cedric H L Shackleton1, Jonathan J Deeks3, Irina Bancos16 & Wiebke Arlt12,17


1Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; 2Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK; 3Institute of Applied Health Research, University of Birmingham, Birmingham, UK; 4Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital, Athens, Greece; 5Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland; 6Department of Endocrinology, University Hospital Centre Zagreb, Zagreb, Croatia; 7Service d’Endocrinologie, Centre Hospitalier Universitaire, Hopital du Haut Leveque, Pessac, France; 8Department of Endocrinology, University Hospital Galway, Galway, Ireland; 9Department of Endocrinology, Haukeland University Hospital, Bergen, Norway; 10Endocrinology in Charlottenburg, Berlin, Germany; 11Department of Medicine III and Institute of Clinical Chemistry and Laboratory Medicine, Technische Universitat Dresden, Dresden, Germany; 12Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital, University of Wuerzburg, Wuerzburg, Germany; 13Department for Obesity, Reproductive and Metabolic Disorders, University of Belgrade, Belgrade, Serbia; 14Division of Internal Medicine I, University of Turin, San Luigi Hospital, Turin, Italy; 15Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany; 16Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA; 17NIHR Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK


Background: Benign adrenal tumours (AT) can be non-functioning (NFAT) or associated with cortisol excess, as indicated by failure to suppress serum morning cortisol to <50 nmol/l in the 1mg-dexamethasone suppression test (1 mg-DST). The latter group divides into patients with clinically overt signs of cortisol excess (adrenal Cushing’s syndrome, CUSH) and patients lacking CUSH signs (mild autonomous cortisol excess, MACE). Smaller series and a recent meta-analysis reported a high prevalence of obesity, type 2 diabetes and hypertension in MACE. However, large-scale prospective data investigating the metabolic impact of MACE are lacking.

Methods: We included 1309 prospectively recruited patients with benign ATs who underwent 1 mg-DST assessment as part of the ENSAT EURINE-ACT study. All patients provided a 24-h urine for mass spectrometry-based urine steroid excretion profiling. Results were compared to 127 healthy controls, using a sex-, BMI- and age-adjusted linear regression model.

Results: NFAT, MACE and CUSH were diagnosed in 50%, 45% and 5% of patients, respectively. Prevalence of metabolic disease increased with the degree of cortisol excess (hypertension: NFAT 64%, MACE 76%, CUSH 72%; type 2 diabetes: NFAT 20%, MACE 28%, CUSH 26%; osteoporosis: NFAT 33%, MACE 47%, CUSH 63%; all P<0.01 by Fisher’s exact test). Urine steroid metabolome analysis identified specific signatures that correlated with the degree of cortisol excess and clinical outcomes. Patients with cortisol excess, hypertension and diabetes had higher urinary glucocorticoid excretion than those without comorbidities. Patients with cortisol excess and osteoporosis had decreased urinary androgens, suggesting a more pronounced glucocorticoid-induced adrenal suppression.

Conclusions: Cortisol excess is highly prevalent in benign ATs and associated with an increased burden of metabolic comorbidities. The urinary adrenal steroid metabolome provides a tool for metabolic risk stratification and may identify those patients who can benefit from definitive treatment of cortisol excess, e.g. tumour removal in patients with MACE.

Article tools

My recent searches

No recent searches.