Endocrine Abstracts (2017) 50 OC2.1 | DOI: 10.1530/endoabs.50.OC2.1

Mild autonomous cortisol excess in adrenal incidentalomas - metabolic disease burden and urinary steroid metabolome in 1201 prospectively recruited patients

Alessandro Prete1, Angela E Taylor1, Alice J Sitch2, Lorna C Gilligan1, Dimitra Vassiliadi3, Urzula Ambroziak4, Katharina Lang1, Darko Kastelan5, Antoine Tabarin6, M Conall Dennedy7, Grethe Æstrøm Ueland8, Marcus Quinkler9, Jimmy Rusdian Masjkur10, Martin Fassnacht11, Miomira Ivovic12, Massimo Terzolo13, Felix Beuschlein14, Konstantinos Manolopoulos1, Stylianos Tsagarakis3, Cedric H L Shackleton1, Jonathan J Deeks2, Irina Bancos15 & Wiebke Arlt1


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


Background: Adrenal incidentalomas (AI) are found in approximately 5% of the adult population. Most AIs are benign; however, small-scale studies have indicated that 20–50% of patients harbouring a benign AI show biochemical evidence of mild autonomous cortisol excess (MACE), previously termed subclinical Cushing’s syndrome. MACE is differentiated into MACE-1 (serum cortisol after overnight suppression with 1 mg dexamethasone (1 mg-DST) 50–140 nmol/l) and MACE-2 (1 mg-DST serum cortisol >140 nmol/l). MACE patients do not show clinically overt signs of Cushing’s, but previous series have suggested an increased risk of metabolic disease. However, large-scale data about the metabolic impact of MACE are lacking.

Methods: We included 1201 AI patients with benign adrenocortical adenoma and 1mg-DST results from the prospective multi-centre EURINE-ACT study. All patients underwent detailed clinical phenotyping and provided a 24 h urine sample. Results of mass spectrometry-based urinary steroid profiling were compared to 162 healthy controls and 56 patients with clinically overt adrenal Cushing’s syndrome, using a linear regression model adjusting for sex and age.

Results: MACE was found in 48% of patients (MACE-1 37%, MACE-2 11%), while 52% had non-functioning (NF) AIs. MACE was more frequent in women (NF: 64%, MACE-1: 67%; MACE-2: 77%). MACE AIs had a larger tumour diameter (median 32 mm vs 22 mm in NF) and were more often bilateral (31% vs 17% in NF). Metabolic disease burden increased with severity of cortisol excess (hypertension: NF 64%, MACE-1 67%, MACE-2 71%; type 2 diabetes: NF 18%, MACE-1 21%, MACE-2 25%). Urinary steroid profiling revealed significantly lower androgen and androgen precursor excretion and increased cortisol metabolite excretion in both MACE and Cushing’s; both groups also showed significantly decreased 5a-reductase activity (all P<0.001).

Conclusions: MACE is highly prevalent in AIs and carries an increased metabolic disease burden. The MACE steroid metabolome signature is highly similar to Cushing’s, including reduced glucocorticoid inactivation via 5a-reductase.

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