我们旨在评估我们双侧肾上腺偶然发现瘤（BAI）患者队列中，九带鬣蜥重复含有5（ARMC5）基因缺陷的患病率，并评估基因型-表型相关性的可能存在。本交叉研究在三级医疗中心进行。共有72名BAI患者纳入研究。收集了以下数据：早晨促肾上腺皮质激素（ACTH）浓度；1毫克隔夜地塞米松抑制试验（F-1mgDST）后的皮质醇水平；尿游离皮质醇（UFC）水平；肾上腺肿块直径；以及与超重/肥胖、动脉高血压、糖尿病、血脂异常、心血管事件、非相关肿瘤、骨质疏松症、甲状腺结节疾病和原发性甲状旁腺功能亢进症的关联。在所有患者及术后肾上腺组织中进行了ARMC5生殖细胞系和体细胞系致病变体的搜索。轻度自主皮质醇分泌（MACS+, 定义为F-1mgDST > 1.8微克/分升）患者中，ARMC5生殖细胞系致病变体的患病率为18.8%。在没有MACS的患者中未检测到ARMC5生殖细胞系致病变体。此外，在没有ARMC5生殖细胞系致病变体的六名患者的肾上腺组织中也发现了ARMC5体细胞系致病变体。F-1mgDST水平 > 5 微克/分升对于识别ARMC5生殖细胞系致病变体的存在具有较低的敏感性，但具有90.5%的特异性。我们未发现任何能预测ARMC5突变存在的临床参数。在MACS+ BAI患者中，乙状腺5基因生殖细胞系致病变体较为常见。需要进一步研究来阐明体细胞系ARMC5致病变体在其他野生型（WT）患者的肾上腺肿瘤发展中的病理生理学作用。© 作者 2023。由牛津大学出版社代表欧洲内分泌学会出版。

We aimed to evaluate the prevalence of armadillo repeat-containing 5 (ARMC5) genetic defects in our cohort of bilateral adrenal incidentaloma (BAI) patients and to evaluate the possible existence of genotype-phenotype correlations.Cross-sectional study.Tertiary care center.72 BAI patients.The following data have been collected: morning adrenocorticotropic hormone (ACTH) concentrations; cortisol levels after 1 mg overnight dexamethasone suppression test (F-1mgDST); urinary free cortisol (UFC) levels; diameter of the adrenal masses; and the association with overweight/obesity, arterial hypertension, diabetes mellitus, dyslipidemia, cardiovascular events, unrelated neoplasia, osteoporosis, thyroid nodular disease, and primary hyperparathyroidism. A search for ARMC5 germline and somatic pathogenic variants was performed in all patients and in the adrenal tissue of patients operated on, respectively.The prevalence of germline ARMC5 pathogenic variants among patients with mild autonomous cortisol secretion (MACS+, defined as F-1mgDST > 1.8 µg/dL) was 18.8%. No germline pathogenic variants were detected in patients without MACS. Moreover, somatic ARMC5 pathogenic variants were also found in the adrenal tissue of six patients without germline ARMC5 variants. The F-1mgDST levels >5 µg/dL predicted with a poor sensitivity but a 90.5% specificity in identifying the presence of ARMC5 germline pathogenic variants. We did not find any clinical parameter predictive of the ARMC5 mutation presence.In MACS+ BAI patients, germline ARMC5 gene pathogenic variants are frequent. Further studies are needed to elucidate the pathophysiological role of somatic ARMC5 pathogenic variants on adrenal tumor development in otherwise wild-type (WT) patients.© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology.