原发性双侧肾上腺大结节增生的临床特征和疗效分析

Clinical characteristics and therapeutic efficacy analysis of primary bilateral macronodular adrenal hyperplasia

摘要:

目的 分析原发性双侧肾上腺大结节增生（primary bilateral macronodular adrenal hyperplasia，PBMAH）患者临床特征及不同手术方式的疗效。方法 回顾性分析从2011年1月至2021年8月就诊于重庆医科大学附属第一医院被诊断为单侧肾上腺腺瘤（unilateral adrenal adenoma，UAA）所致促肾上腺皮质激素（adrenocorticotropic hormone，ACTH）非依赖性库欣综合征（Cushing’s syndrome，CS）患者119例和PBMAH患者34例的临床表现、代谢相关疾病、激素分泌水平和影像学特征等临床资料，通过与UAA患者比较以分析PBMAH的临床特征，同时比较PBMAH患者手术前后临床表现、代谢性疾病、激素分泌水平等变化情况以评估不同手术方式对PBMAH的疗效。结果 PBMAH患者与UAA患者临床特征有较明显差异。PBMAH组诊断时平均年龄为（49.8±13.1）岁，明显高于UAA组的（43.0±11.6）岁（P=0.016）；PBMAH组男女发病率相似，而UAA组女性明显高于男性（P<0.001）；PBMAH患者主要表现为亚临床库欣综合征（subclinical Cushing’s syndrome，SCS）（55.9%），以高血压、糖尿病等代谢相关疾病最为常见。在激素分泌水平方面，PBMAH组皮质醇增高水平明显低于UAA组，尤其是16：00、24：00血清皮质醇和24 h尿游离皮质醇；10例患者具有家族遗传病史并对其行基因检测提示ARMC5基因突变。影像学检查显示双侧肾上腺弥漫性大结节样增生，而UAA患者多为单侧单发腺瘤。治疗方面，SCS PBMAH患者行单侧肾上腺切除术临床缓解率高（100%），而伴库欣貌的PBMAH患者单侧切除术后临床缓解率为50%，16.7%的患者缓解后复发。单侧肾上腺切除术后肾上腺皮质功能不全的发生率（28.6%）明显低于双侧肾上腺手术（100%）。结论 PBMAH是一个家族遗传性疾病，发病年龄较高，常表现为SCS，多以高血压、糖尿病为首发症状。PBMAH伴SCS患者建议行单侧肾上腺全切除术，伴有明显CS症状患者建议行一侧全切对侧大部分切除术。

Abstract:

Objective To analyze the clinical characteristics and the efficacy of different surgical approaches of patients with primary bilateral macronodular adrenal hyperplasia（PBMAH）.Methods Clinical data of 119 patients diagnosed with adrenocorticotropic hormone（ACTH）-independent Cushing’s syndrome（CS） due to unilateral adrenal adenoma（UAA） and 34 patients with PBMAH in our hospital from January 2011 to August 2021 were analyzed retrospectively. Their clinical data such as clinical features，metabolic-related diseases，hormone secretion levels and imaging features were compared to summarize the clinical features of PBMAH. At the same time，the changes in clinical manifestations，metabolic diseases and hormone secretion levels of PBMAH patients before and after surgery were compared to to evaluate the therapeutic efficacy of different surgical procedures on PBMAH.Results Both PBMAH patients and UAA patients had significantly different clinical manifestations. The mean age at diagnosis was （49.8±13.1） years in the PBMAH group，which was significantly higher than that of the UAA group’s（43.0±11.6） years（P=0.016）. The incidence of PBMAH group was similar in both genderes，while the UAA group was significantly higher in women than in men（P<0.001）. Subclinical Cushing’s syndrome（SCS）（55.9%） was the main manifestation of PBMAH patients，and metabolic-related diseases such as hypertension and diabetes were the most common. In terms of hormone secretion levels，the cortisol level in the PBMAH group was significantly lower than that in the UAA group，especially serum cortisol at 16：00，24：00 and 24-hour urinary free cortisol. And 10 patients had a family history of genetic disorders，and were tested for mutations in the ARMC5 gene. Imaging showed diffuse large nodular hyperplasia of the adrenal glands bilaterally，whereas UAA patients had unilateral solitary adenomas. For treatment，PBMAH patients with SCS underwent unilateral adrenalectomy with a high clinical remission rate（100%），while PBMAH patients with Cushing’s appearance had a clinical remission rate of 50% after unilateral resection，and 16.7% of patients relapsed. And the incidence of adrenocortical insufficiency after unilateral adrenalectomy（28.6%） was significantly lower than that after bilateral adrenal surgery（100%）.Conclusion PBMAH is a familial hereditary disease with a higher age of onset，often manifesting as SCS，with hypertension and diabetes as the first symptoms. PBMAH patients combined with SCS are recommended to undertake unilateral total adrenalectomy. Patients with obvious symptoms of CS are recommended to undertake total adrenalectomy on one side and major adrenalectomy on the opposite side.