• Alessandro Prete, Anuradhaa Subramanian, Irina Bancos, Vasileios Chortis, Stylianos Tsagarakis, Katharina Lang, Magdalena Macech, Danae A Delivanis, Ivana D Pupovac, Giuseppe Reimondo, Ljiljana V Marina, Timo Deutschbein, Maria Balomenaki, Michael W O'Reilly, Lorna C Gilligan, Carl Jenkinson, Tomasz Bednarczuk, Catherine D Zhang, Tina Dusek, Aristidis Diamantopoulos, Miriam Asia, Agnieszka Kondracka, Dingfeng Li, Jimmy R Masjkur, Marcus Quinkler, Grethe Å Ueland, M Conall Dennedy, Felix Beuschlein, Antoine Tabarin, Martin Fassnacht, Miomira Ivović, Massimo Terzolo, Darko Kastelan, William F Young, Konstantinos N Manolopoulos, Urszula Ambroziak, Dimitra A Vassiliadi, Angela E Taylor, Alice J Sitch, Krishnarajah Nirantharakumar, Wiebke Arlt, ENSAT EURINE-ACT Investigators*, and ENSAT EURINE-ACT Investigators.
• The Institute of Metabolism and Systems Research, University of Birmingham, Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, and Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom (A.P., V.C., K.L.).
• Ann. Intern. Med. 2022 Mar 1; 175 (3): 325-334.

BackgroundBenign adrenal tumors are commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion (MACS) is regularly diagnosed, but its effect on cardiometabolic disease in affected persons is ill defined.ObjectiveTo determine cardiometabolic disease burden and steroid excretion in persons with benign adrenal tumors with and without MACS.DesignCross-sectional study.Setting14 endocrine secondary and tertiary care centers (recruitment from 2011 to 2016).Participants1305 prospectively recruited persons with benign adrenal tumors.MeasurementsCortisol excess was defined by clinical assessment and the 1-mg overnight dexamethasone-suppression test (serum cortisol: <50 nmol/L, nonfunctioning adrenal tumor [NFAT]; 50 to 138 nmol/L, possible MACS [MACS-1]; >138 nmol/L and absence of typical clinical Cushing syndrome [CS] features, definitive MACS [MACS-2]). Net steroid production was assessed by multisteroid profiling of 24-hour urine by tandem mass spectrometry.ResultsOf the 1305 participants, 49.7% had NFAT (n = 649; 64.1% women), 34.6% had MACS-1 (n = 451; 67.2% women), 10.7% had MACS-2 (n = 140; 73.6% women), and 5.0% had CS (n = 65; 86.2% women). Prevalence and severity of hypertension were higher in MACS-2 and CS than NFAT (adjusted prevalence ratios [aPRs] for hypertension: MACS-2, 1.15 [95% CI, 1.04 to 1.27], and CS, 1.37 [CI, 1.16 to 1.62]; aPRs for use of ≥3 antihypertensives: MACS-2, 1.31 [CI, 1.02 to 1.68], and CS, 2.22 [CI, 1.62 to 3.05]). Type 2 diabetes was more prevalent in CS than NFAT (aPR, 1.62 [CI, 1.08 to 2.42]) and more likely to require insulin therapy for MACS-2 (aPR, 1.89 [CI, 1.01 to 3.52]) and CS (aPR, 3.06 [CI, 1.60 to 5.85]). Urinary multisteroid profiling revealed an increase in glucocorticoid excretion from NFAT over MACS-1 and MACS-2 to CS, whereas androgen excretion decreased.LimitationsCross-sectional design; possible selection bias.ConclusionA cardiometabolic risk condition, MACS predominantly affects women and warrants regular assessment for hypertension and type 2 diabetes.Primary Funding SourceDiabetes UK, the European Commission, U.K. Medical Research Council, the U.K. Academy of Medical Sciences, the Wellcome Trust, the U.K. National Institute for Health Research, the U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.

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