Enhanced Chronic Inflammation and Increased Branched-Chain Amino Acids in Adrenal Disorders: A Cross-Sectional Study.

Context: Patients with adrenal hormone excess demonstrate increased cardiovascular (CV) risk and mortality.

Objective: We aimed to determine the effect of adrenal disorders on the inflammation marker glycoprotein acetylation (GlycA), total branched-chain amino acids (BCAAs), ketone bodies, and the gut microbiome-derived metabolites trimethylamine N-oxide (TMAO) and betaine.

Methods: We conducted a single-center cross-sectional study of patients with nonfunctioning adenomas (NFAs), mild autonomous cortisol secretion (MACS), primary aldosteronism (PA), Cushing syndrome (CS), pheochromocytoma/paragangliomas (PPGLs), other benign or malignant adrenal masses, and adrenocortical carcinoma (ACC) between January 2015 and July 2022 (n = 802). Referent individuals included participants in the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study (n = 5241). GlycA, BCAAs, ketone bodies, TMAO, and betaine were measured using nuclear magnetic resonance spectroscopy. Multivariable logistic analyses were adjusted for age, sex, body mass index, smoking, hypertension, diabetes mellitus, and statin therapy.

Results: In age- and sex-adjusted comparison to referent individuals, increased GlycA was noted in all patient categories, increased BCAAs in NFA, MACS, CS, PA, and ACC, increased TMAO in patients with other malignant adrenal masses, increased betaine in NFA and MACS, and increased ketone bodies in NFA, CS, and ACC. Essentially similar findings were observed in fully adjusted analysis and after exclusion of participants with diabetes and CV disease.

Conclusion: Patients with functioning and nonfunctioning adrenal masses demonstrated increased GlycA and BCAAs, biomarkers associated with adverse cardiometabolic disorders and mortality. Patients with NFA demonstrated an adverse metabolic profile similar to patients with MACS and CS.