单侧肾上腺切除作为促肾上腺皮质激素非依赖性肾上腺大结节增生首选治疗方法的可行性分析

Feasibility analysis of unilateral adrenalectomy as the first choice for the treatment of adrenocorticotropin-independent macronodular adrenal hyperplasia

目的:本研究拟对促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)非依赖性肾上腺大结节增生(ACTH-independent macronodular adrenal hyperplasia,AIMAH)患者行单侧肾上腺切除术后的临床价值进行评估,以探讨该方法作为治疗AIMAH首选方法的可行性。方法:回顾性分析2008—2019年46例行单侧肾上腺切除术后的AIMAH患者的临床资料。男20例,女26例;年龄31~72岁,平均(55.13±8.89)岁;亚临床型6例,临床型33例,危重型7例。患者在术前均有不同程度的临床表现,高血压41例,超重或肥胖27例,上午8点血皮质醇浓度升高20例,24 h尿游离皮质醇升高42例。2 mg地塞米松抑制试验在41例中进行,均报告不被抑制;8 mg地塞米松抑制试验在40例中进行,均报告不被抑制。CT影像上显示双侧肾上腺明显增大伴多个大小不等结节。46例患者行单侧肾上腺全切术。术后患者康复出院,嘱患者术后第1、3、6、9和12个月之后每半年随访。应用SPSS 23.0软件进行统计分析,使用GraphPad Prism 8进行绘图。结果:经手术切除的标本可见多个大小不等的结节,切面呈金黄色。共42例随访,平均随访26.93个月,4例失访。随访期内,未复发29例,复发13例。未复发患者库欣综合征症状好转,血压较术前下降,平均收缩压下降22.30 mmHg(P=0.001),平均舒张压下降16.05 mmHg(P=0.003)。平均8点血皮质醇浓度下降8.23μg/dL(P<0.000 1),平均24 h尿游离皮质醇下降273.21μg/24 h(P<0.000 1),平均ACTH浓度升高6.40 pg/mL(P=0.006 2)。CT检查发现,未复发患者的对侧肾上腺在随访期内无显著变化。6例亚临床AIMAH患者均未复发,血压较术前降低或恢复正常。13例患者在术后有过一定时间的缓解,但5~63个月后复发,平均27.38个月,中位复发时间18个月。复发患者行对侧肾上腺全切或部分切术,46例患者手术累计59例次。结论:AIMAH患者应诊断分型。单侧肾上腺切除应被推荐作为AIMAH患者的首选治疗方式,这可以避免双侧同时切除后肾上腺皮质激素分泌不足导致的各种并发症,且对于3种亚型的患者术后均可获益。在术后,患者应定期随访,对侧肾上腺的异常增大应警惕复发可能。一旦复发,对侧肾上腺需要被处理。长期来看,单侧肾上腺切除可能使患者终身受益,患者有一定的概率无需处理对侧肾上腺。

Objective: To evaluate the clinical value of patients with adrenocorticotropic hormone-independent macronodular adrenal hyperplasia(AIMAH) after unilateral adrenalectomy in order to explore the feasibility of this method as the first choice for the treatment of AIMAH. Methods: The clinical data of 46 patients with AIMAH after unilateral adrenalectomy from 2008 to 2019 were analyzed retrospectively. There were 20 males and 26 females, with an average age of(55.13±8.89) years. There were 6 cases of subclinical type, 33 cases of clinical type and 7 cases of high-risk type. All patients had different clinical features before surgery, 41 patients with hypertension, 27 patients with overweight or obesity, 20 patients with increasing blood cortisol concentration at 8 am, 42 patients with increasing 24-hour urinary free cortisol. Failed to suppress cortisol secretion was observed in all 41 patients conducted with 2 mg dexamethasone suppression tests and in all 40 patients conducted with 8 mg dexamethasone suppression tests. On CT images, bilateral adrenal glands were obviously enlarged with multiple unequal sized nodules. Forty-six patients underwent unilateral adrenalectomy. The patients were discharged from hospital after operation. They were asked to follow up at 1, 3, 6, 9 and 12 months after surgery and thereafter every six months. Statistical analysis was performed using SPSS 23.0 software, and GraphPad Prism 8 was used for drawing. Results: The resected specimen showed multiple nodules of various sizes, and the section was golden yellow. A total of 42 people were followed up, with an average follow-up of 26.93 months, and 4 were lost to follow-up. During the follow-up period, 29 patients did not recur and 13 patients recurred. The patients without recurrence had Cushing’s symptoms improved, blood pressure decreased. The mean systolic blood pressure decreased by 22.30 mmHg(P=0.001), and the mean diastolic blood pressure decreased by 16.05 mmHg(P=0.003). The blood cortisol concentration at 8 am decreased by 8.23 μg/dL(P<0.000 1), the 24-hour urinary free cortisol decreased by 273.21 μg/24 h(P<0.000 1), and the average ACTH concentration increased by 6.40 pg/mL(P=0.006 2). CT examination showed that there was no significant change in the contralateral adrenal gland of the patients without recurrence during the follow-up period. There was no recurrence in 6 patients with subclinical AIMAH, and the blood pressure decreased or returned to normal. Thirteen patients had a certain time of remission after surgery, but recurred after 5-63 months, with an average of 27.38 months and a median relapse time of 18 months. Recurrent patients underwent total or partial resection of the contralateral adrenal gland. A total of 59 operations were performed in 46 patients. Conclusion: Patients with AIMAH should be classified. Unilateral adrenalectomy should be recommended as the first choice for the treatment of patients with AIMAH, which can avoid various complications caused by insufficient secretion of corticosteroids after bilateral adrenalectomy simultaneously, and can benefit the patients of all three subtypes after surgery. Patients should be followed up regularly after surgery. The abnormal enlargement of contralateral adrenal gland should be alert to the possibility of recurrence. Once it recurs, the contralateral adrenal gland needs to be treated. In the long run, unilateral adrenalectomy may benefit the patient for life, and there is a certain chance that the patient does not need to deal with the contralateral adrenal gland.