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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 A.; Dennedy, M. Conall; Beuschlein, Felix; Tabarin, Antoine; Fassnacht, Martin; Ivovic, Miomira; Terzolo, Massimo; Kastelan, Darko; Young, William F.; Manolopoulos, Konstantinos N.; Ambroziak, Urszula; Vassiliadi, Dimitra A.; Taylor, Angela E.; Sitch, Alice J.; Nirantharakumar, Krishnarajah and Arlt, Wiebke (2022): Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors A Cross-Sectional Multicenter Study. In: Annals of Internal Medicine, Vol. 175, No. 3: pp. 325-334

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Background: Benign 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. 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.

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