单中心985例行肾上腺手术治疗的库欣综合征患者临床特点分析

Analysis of clinical characteristics of 985 patients with Cushing's syndrome treated with adrenal surgery in a single center

目的探讨行肾上腺手术治疗的库欣综合征(CS)患者的临床特点及治疗方式。方法回顾性分析2002年8月至2022年8月于北京协和医院行手术治疗的985例CS患者的临床资料。男210例,女775例;年龄(43.33±13.49)岁,男性年龄高于女性[(45.53±14.39)岁与(42.68±13.16)岁,P=0.016]。本组患者术前选择手术方法的原则为:对于促肾上腺皮质激素(ACTH)非依赖性CS,单侧单发病变行肾上腺肿瘤切除术;单侧多发病变行单侧肾上腺切除术;双侧病变先切除体积较大一侧肿瘤,根据随访结果决定是否行对侧手术。术前怀疑皮质癌患者均行R0切除(肿瘤完整切除,镜下切缘阴性),如肿瘤直径≥6cm,则行开放手术。总结CS患者的临床特点,分析临床症状谱、病因谱,以及相应的治疗方法。结果985例中ACTH非依赖性CS占92.8%(914/985),ACTH依赖性CS占7.2%(71/985)。结合术后病理结果确诊,肾上腺腺瘤最常见,占75.94%(748/985),其次为PBMAH(11.37%,112/985)、库欣病(4.26%,42/985)、PPNAD(3.25%,32/985)、EAS(2.94%,29/985)、皮质癌(2.23%,22/985)。临床表现方面,满月脸、多血质面容、水牛背、向心性肥胖及体重增加较为常见,上述单一症状发生率均>30%。激素分泌方面,ACTH依赖性CS患者皮质醇水平明显高于ACTH非依赖性CS[(38.42±18.21)μg/dl与(22.02±9.48)μg/dl,P<0.001]。亚临床型皮质腺瘤患者(258例)早8时血皮质醇[(16.61±6.78)μg/dl]及24h尿游离皮质醇[103.65(59.83,175.70)μg/24h]低于其他类型患者(P<0.001)。治疗方面,除4例(0.4%)皮质癌因肿瘤较大行开放手术外,余981例均行腹腔镜手术,其中经腹途径占2.24%(22/981),经腹膜后途径占97.76%(959/981)。皮质腺瘤患者中单侧670例(89.57%),双侧78例(10.43%);单侧腺瘤采用腹腔镜肾上腺肿瘤切除/次全切除术;双侧腺瘤者中,4例因CS症状严重同期切除双侧肾上腺肿瘤,余74例均根据肿瘤大小及个数分期行单纯肿瘤切除/肾上腺全切/次全切除术。22例皮质癌患者中,2例因肿瘤局部浸润,经穿刺活检确诊后行米托坦新辅助治疗,后行R0切除;另20例均行R0切除。在EAS和库欣病患者中,分别有62.07%(18/29)和23.81%(10/42)因CS症状严重采用同期双侧靶腺切除术;112例PBMAH和32例PPNAD,初始治疗均采用单侧肾上腺切除或次全切除术,后续根据随访情况,决定是否行对侧肾上腺全切除或次全切除术。结论泌尿外科收治的CS患者病因谱以肾上腺疾病为主,库欣病少见。症状谱中,蹲起困难、骨折少见。单侧肾上腺病变主要的治疗方法为肿瘤切除或单侧肾上腺切除术。对于双侧病变中ACTH依赖性CS患者,建议行双侧肾上腺切除术,术后补充激素;对于ACTH非依赖性CS患者,建议先行单侧肾上腺切除术,术后根据随访结果制订个体化治疗方案。

Objective To investigate the etiological spectrum,clinical features,and surgical treatment of patients with Cushing's syndrome(CS)who underwent adrenal surgery.Methods From August 2002 to August 2022,the clinical data of 985 patients with Cushing's syndrome who underwent surgical treatment in the department of urology,Peking Union Medical College Hospital were retrospectively analyzed.There were 210 males and 775 females.The average age was 43.33±13.49 years old.The age of males was older than that of females(45.53±14.39 vs.42.68±13.16 years,P=0.016).The principle of preoperative surgical method selection for patients in this group was described as follow.For adrenocorticotropin(ACTH)independent CS,adrenal tumor resection was considered for unilateral solitary lesions and unilateral adrenalectomy was considered for unilateral multiple lesions.For bilateral lesions,the larger tumor was removed first,and the contralateral operation was decided according to the follow-up results.Patients with suspicion of cortical cancer are subjected to R0 resection,and open surgery was performed if the tumor diameter is≥6 cm.The clinical characteristics of CS patients were summarized.The clinical symptom characters,etiology spectrum and the corresponding selection principles of surgical methods were analyzed.Results Among the 985 cases,ACTH-independent CS accounted for 92.8%(914/985),and ACTH-dependent CS accounted for 7.2%(71/985).According to the postoperative pathological results,ACTH-independent CS was the most common,among which adrenal adenoma was the most common 75.94%(748/985),PBMAH 11.37%(112/985),Cushing's disease 4.26%(42/985),PPNAD 3.25%(32/985),EAS 2.94(29/985),cortical carcinoma 2.23%(22/985).In terms of clinical manifestations,full moon face,bloody face,buffalo back,central obesity and weight gain were more common.The incidence of the above single symptoms was>30%.In terms of hormone secretion,the cortisol level of ACTH-dependent CS patients was significantly higher than that of ACTH-independent CS(P<0.001).Cortisol[(16.61±6.78)μg/dl]and 24h-UFC[103.65(59.83,175.70)μg/24h]in patients with subclinical cortical adenoma were lower than those in other types of patients(P<0.001).Among the patients with bilateral adenomas,4 patients underwent simultaneous resection of bilateral adrenal tumors due to severe CS symptoms,and the remaining 74 patients underwent two-stage simple tumor resection,total adrenalectomy or subtotal adrenalectomy according to the size and number of tumors.Of the 22 patients with cortical carcinoma,2 patients underwent R0 resection after neoadjuvant therapy with mitotane after being diagnosed by needle biopsy due to local infiltration of the tumor.In patients with EAS and Cushing's disease,62.07%(18/29)and 23.81%(10/42)were treated with simultaneous bilateral target gland resection due to severe CS symptoms,respectively.In 112 cases of PBMAH and 32 cases of PPNAD,the initial treatment was unilateral adrenalectomy or subtotal adrenalectomy,and the follow-up was continued to decide whether to perform contralateral adrenalectomy or subtotal adrenalectomy.Conclusions The etiological spectrum of CS patients admitted to the urology department is different from that of the overall CS,and is dominated by adrenal disease,and Cushing's disease is rare.Due to the different etiological spectrum,the patient's symptom spectrum is different,and difficulty in squatting and fracture are rare.The main treatment for unilateral adrenal disease is tumor resection or unilateral adrenalectomy.For ACTH-dependent CS in bilateral lesions,bilateral adrenalectomy is recommended,and hormone supplementation is recommended after surgery.For ACTH-independent CS,unilateral adrenalectomy is recommended first,and individualized treatment plans are formulated based on the results of follow-up.