TY - JOUR
T1 - Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors A Cross-Sectional Multicenter Study
AU - ENSAT EURINE-ACT Investigators
AU - Prete, Alessandro
AU - Subramanian, Anuradhaa
AU - Bancos, Irina
AU - Chortis, Vasileios
AU - Tsagarakis, Stylianos
AU - Lang, Katharina
AU - Macech, Magdalena
AU - Delivanis, Danae A.
AU - Pupovac, Ivana D.
AU - Reimondo, Giuseppe
AU - Marina, Ljiljana V.
AU - Deutschbein, Timo
AU - Balomenaki, Maria
AU - O’Reilly, Michael W.
AU - Gilligan, Lorna C.
AU - Jenkinson, Carl
AU - Bednarczuk, Tomasz
AU - Zhang, Catherine D.
AU - Dusek, Tina
AU - Diamantopoulos, Aristidis
AU - Asia, Miriam
AU - Kondracka, Agnieszka
AU - Li, Dingfeng
AU - Masjkur, Jimmy R.
AU - Quinkler, Marcus
AU - Ueland, Grethe
AU - Dennedy, M. Conall
AU - Beuschlein, Felix
AU - Tabarin, Antoine
AU - Fassnacht, Martin
AU - Ivović, Miomira
AU - Terzolo, Massimo
AU - Kastelan, Darko
AU - Young, William F.
AU - Manolopoulos, Konstantinos N.
AU - Ambroziak, Urszula
AU - Vassiliadi, Dimitra A.
AU - Taylor, Angela E.
AU - Sitch, Alice J.
AU - Nirantharakumar, Krishnarajah
AU - Arlt, Wiebke
AU - Glöckner, Stephan
AU - Sinnott, Richard O.
AU - Stell, Anthony
AU - Fragoso, Maria Candida B.V.
AU - Simunov, Bojana
AU - Cazenave, Sarah
AU - Haissaguerre, Magalie
AU - Chang, Alice
AU - Erickson, Dana
N1 - Publisher Copyright:
© 2022 American College of Physicians. All rights reserved.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - 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.
AB - 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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U2 - 10.7326/M21-1737
DO - 10.7326/M21-1737
M3 - Article
C2 - 34978855
AN - SCOPUS:85126490824
SN - 0003-4819
VL - 175
SP - 325
EP - 334
JO - Annals of internal medicine
JF - Annals of internal medicine
IS - 3
ER -