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

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50μg/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。

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.