复发库欣病患者二次手术治疗后缓解影响因素分析

郑舒颖; 孙昱皓; 王宝锋; 孙青芳; 卞留贯

doi:10.12025/j.issn.1008-6358.2021.20210704

复发库欣病患者二次手术治疗后缓解影响因素分析

Analysis of influencing factors of remission in patients with recurrent Cushing's disease after reoperation

摘要

摘要:
目的分析接受再次手术的复发性库欣病患者的缓解率及其影响因素。
方法回顾性分析2003年1月至2018年12月行第2次经蝶手术的22例复发性库欣病患者（随访超过6个月）的临床资料。分析患者第2次术前生化指标、双侧岩下窦静脉采血结果、MRI结果。同时评估术后血清皮质醇、24 h尿游离皮质醇（urinary free cortisol，UFC）和病理结果。术后缓解定义为术后血皮质醇小于50 μg/L或者24 h UFC值处于正常范围。分析两次术前MRI结果、促肾上腺皮质激素（ACTH）水平、24 h UFC、肿瘤大小等因素与第2次术后缓解的相关性。
结果 16例（72.7%）患者在第2次术后获得缓解，平均随访时间为64.5个月。22例患者初次术前均有明显库欣病影像学证据，其中有8例（36.4%）再次手术前无复发的明显影像学证据。MRI显示存在垂体占位的14例患者中10例（71.4%）再手术后缓解；8例MRI未显示明显肿瘤的患者中6例于再次手术后缓解。微腺瘤患者（75.0%，15/20）的再手术后缓解率略优于大腺瘤患者（50.0%，1/2），但差异无统计学意义。缓解患者二次术前ACTH和UFC水平均低于术后未缓解组，但差异无统计学意义。二次术后，病理结果显示有ACTH阳性腺瘤证据的患者有更高的缓解率（86.7% vs 42.9%，P < 0.05），而复发时的年龄较大非手术结果的不利因素。
结论二次手术对于初次手术后复发的库欣病患者是一个较好的选择，而其远期效果须延长随访时间进一步验证，缓解相关因素须增加病例进一步筛选。

Abstract:
Objective To analyze the remission rate of patients with recurrent Cushing's disease (CD) and its related factors.
Methods Clinical data of 22 patients with recurrent CD who underwent a second transsphenoidal surgery from Jan. 2003 to Dec. 2018 were retrospectively analyzed. Patients were followed up for over 6 months. Biochemical indexes, bilateral inferior petrosal sinus sampling (BIPSS) results, and MRI results before the second surgery were analyzed. Postoperative serum cortisol, 24-hour urinary free cortisol (UFC) levels, and postoperative pathology were evaluated. Postoperative remission was defined as postoperative serum cortisol less than 5 μg/L or UFC within the normal range. The correlations between preoperative MRI results, adreno-cortico-tropic-hormone (ACTH) level, UFC level, tumor size, and other factors and remission after the second operation were statistically analyzed.
Results Totally, 16(72.7%) patients achieved remission after the second surgery, with a mean follow-up of 64.5 months. All the 22 patients had obvious imaging evidence before the first operation, among whom 8 cases (36.4%) had no obvious imaging evidence of recurrence before the second operation. Of the 14 patients with MRI showing pituitary adenomas, 10 (71.4%) were in remission after reoperation, and 6 of the 8 patients with negative MRI also benefited from reoperation. The disease control rate after reoperation in patients with microadenoma (75.0%, 15/20) was better than that in patients with macroadenoma (50.0%, 1/2), but there was no statistically significant difference. The levels of ACTH and UFC in the remission patients before the second operation were lower than those in the non-remission group, but the differences were not statistically significant. Patients with pathologic evidence of ACTH-positive adenoma after the second surgery had a higher remission rate (86.7% vs 42.9%, P < 0.05). And older age at the time of recurrence was not an unfavorable factor for the outcome of the surgery.
Conclusions Reoperation is a considerable option for patients with recurrent CD after initial surgery. However, further studies with longer follow-up periods and more cases are needed to confirm the long-term effects of reoperation, and other related factors need to increase the number of cases for further screening.

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