OBJECTIVE 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. DESIGN Cross-sectional study. SETTING Tertiary care center. PARTICIPANTS 72 BAI patients. MAIN OUTCOME MEASURE(S) 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. RESULTS 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. CONCLUSIONS 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.

中文翻译：

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双侧肾上腺偶发瘤患者单中心队列中含有犰狳重复的 5 个突变携带者的患病率和临床特征。

目的 我们旨在评估双侧肾上腺偶发瘤 (BAI) 患者队列中犰狳重复序列 5 (ARMC5) 遗传缺陷的患病率，并评估基因型-表型相关性的可能存在。设计横断面研究。设置 三级护理中心。参与者 72 名 BAI 患者。主要观察指标 收集了以下数据： 早晨促肾上腺皮质激素 (ACTH) 浓度；1 mg 过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；肾上腺肿块的直径；以及与超重/肥胖、动脉高血压、糖尿病、血脂异常、心血管事件、无关肿瘤、骨质疏松症、甲状腺结节病和原发性甲状旁腺功能亢进症的关联。分别在所有患者和接受手术的患者的肾上腺组织中搜索 ARMC5 种系和体细胞致病变异。结果 轻度自主皮质醇分泌（MACS+，定义为 F-1mgDST > 1.8 µg/dL）患者中种系 ARMC5 致病性变异的患病率为 18.8%。在没有 MACS 的患者中未检测到种系致病变异。此外，在六名没有种系ARMC5变异的患者的肾上腺组织中也发现了体细胞ARMC5致病变异。F-1mgDST 水平 >5 µg/dL 的预测灵敏度较差，但在识别 ARMC5 种系致病变异的存在方面具有 90.5% 的特异性。我们没有发现任何预测 ARMC5 突变存在的临床参数。结论 在 MACS+ BAI 患者中，种系 ARMC5 基因致病性变异很常见。需要进一步的研究来阐明体细胞 ARMC5 致病性变异对野生型 (WT) 患者肾上腺肿瘤发展的病理生理学作用。