Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors : A Cross-Sectional Multicenter Study.
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Prete Alessandro, Subramanian Anuradhaa, Bancos Irina, Chortis Vasileios, Tsagarakis Stylianos, Lang Katharina, Macech Magdalena, Delivanis Danae A, Pupovac Ivana D, Reimondo Giuseppe, Marina Ljiljana V, Deutschbein Timo, Balomenaki Maria, O'Reilly Michael W, Gilligan Lorna C, Jenkinson Carl, Bednarczuk Tomasz, Zhang Catherine D, Dusek Tina, Diamantopoulos Aristidis, Asia Miriam, Kondracka Agnieszka, Li Dingfeng, Masjkur Jimmy R, Quinkler Marcus, Ueland Grethe Å, Dennedy M Conall, Beuschlein Felix, Tabarin Antoine, Fassnacht Martin, Ivović Miomira, Terzolo Massimo, Kastelan Darko, Young William F, Manolopoulos Konstantinos N, Ambroziak Urszula, Vassiliadi Dimitra A, Taylor Angela E, Sitch Alice J, Nirantharakumar Krishnarajah, Arlt Wiebke, ENSAT EURINE-ACT Investigators*, ENSAT EURINE-ACT Investigators
Аннотация
OBJECTIVE: To determine cardiometabolic disease burden and steroid excretion in persons with benign adrenal tumors with and without MACS.
DESIGN: Cross-sectional study.
SETTING: 14 endocrine secondary and tertiary care centers (recruitment from 2011 to 2016).
PARTICIPANTS: 1305 prospectively recruited persons with benign adrenal tumors.
MEASUREMENTS: Cortisol 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.
RESULTS: Of 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.
LIMITATIONS: Cross-sectional design; possible selection bias.
CONCLUSION: A cardiometabolic risk condition, MACS predominantly affects women and warrants regular assessment for hypertension and type 2 diabetes.
PRIMARY FUNDING SOURCE: Diabetes 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.