Non-functioning pituitary adenomas with positive immunoreactivity for ACTH behave more aggressively than ACTH immunonegative tumours but do not recur more frequently
Non-functioning pituitary adenomas with positive immunoreactivity for ACTH behave more aggressively than ACTH immunonegative tumours but do not recur more frequently
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DOI：
10.1046/j.1365-2265.2003.01674.x
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发表时间：
2003-01-01
影响因子：
3.2
通讯作者：
Turner, HE
中科院分区：
文献类型：
--
作者：
Bradley, KJ;Wass, JAH;Turner, HE
目的：坊间报道表明，沉默的促皮质性肿瘤表现为侵袭性；然而，缺乏与其他非功能性腺瘤（nfa）的明确比较数据。本研究的目的是，首先，回顾那些对ACTH免疫反应阳性的无功能垂体腺瘤的自然史，其次，通过与现有部门数据的比较，确定该亚群是否比ACTH免疫阴性的NFAs更具侵袭性。方法和患者：1975年至2001年间，28例（16名男性，平均年龄51.3岁）在牛津接受了经蝶窦手术，治疗临床无功能腺瘤，随后的ACTH免疫染色呈阳性。在此期间出现的所有无症状的皮质性肿瘤患者都被纳入分析；其中3名患者随后死亡，但没有人在随访中失踪。平均随访时间为7.4年（0.5-26.9年），并将结果与ACTH免疫阴性的NFAs的部门数据进行比较。这些患者都没有库欣综合征的临床证据。肿瘤侵袭性根据改良的Hardy标准进行分类(1级=微腺瘤（1cm) +/-鞍上延伸，3级=局部侵犯伴骨破坏，肿瘤位于蝶窦/海绵窦，4级=中枢神经系统（CNS）扩散或颅外扩散，即转移）。肿瘤复发被定义为肿瘤大小与第一次术后扫描相比增加，这被用作基线。在28例患者中，79%的患者有视野缺陷，而在整体无功能人群中，这一比例为69% （P = 0.3）。无症状的皮质营养不良组术前影像学（13例CT， 14例MRI和1例脑电图）显示68%为2级腺瘤，32%为3级腺瘤。结果ACTH免疫阳性肿瘤的复发率为32%，平均5.8年（1-16年），与ACTH免疫阴性肿瘤的33%复发率无显著差异（P = 0.9）。2例无症状的皮质性腺瘤患者多次复发；1例复发2次，手术3次，放疗2个疗程；1例复发3次，手术4次，放疗2个疗程，伽玛刀治疗。相比之下，没有ACTH免疫阴性肿瘤患者需要超过一个疗程的肿瘤再生治疗。结论：这是第一个对一系列临床沉默的ACTH免疫阳性肿瘤进行的单中心比较研究，并表明尽管它们不比ACTH免疫阴性肿瘤更经常复发，但当它们重新生长时，它们表现出更强的侵袭性。这一研究的实际意义是，没有证据表明ACTH免疫阳性和免疫阴性的nfa在最初表现时有不同的术后影像学和放疗方案。然而，如果无症状的促皮质性肿瘤再次生长，那么在进一步治疗后，非常仔细的监测是必不可少的。
OBJECTIVES Anecdotal reports have suggested that silent corticotroph tumours behave in an aggressive fashion; however, clear comparative data with other non-functioning adenomas (NFAs) are lacking. The aims of the study were, first, to review the natural history of those non-functioning pituitary adenomas with positive immunoreactivity for ACTH and secondly, to determine whether this subgroup behave more aggressively than ACTH immunonegative NFAs by means of comparison with existing departmental data.METHODS AND PATIENTS Twenty-eight patients (16 men, mean age 51.3 years) who underwent transsphenoidal surgery in Oxford between 1975 and 2001 for clinically non-functioning adenomas where the subsequent immunostaining was positive for ACTH were identified from the patient database. All patients with silent corticotroph tumours who presented during this time period have been included in the analysis; three of the patients have subsequently died but none have been lost to follow-up. The mean follow-up period was 7.4 years (range 0.5-26.9 years) and the results were compared with departmental data for NFAs which were immunonegative for ACTH. None of the patients had clinical evidence of Cushing's syndrome. Tumour invasiveness was classified according to the modified Hardy criteria (Grade 1 = microadenoma (1 cm) +/- suprasellar extension, Grade 3 = local invasion with bony destruction and tumour in sphenoid/cavernous sinus and Grade 4 = central nervous sytem (CNS) spread or extracranial spread, i.e. metastatic). Tumour recurrence was defined as an increase in tumour size compared with the first postoperative scan which was used as a baseline. Visual field defects were documented in 79% of the 28 patients at presentation compared to 69% in the non-functioning population as a whole (P = 0.3). The preoperative imaging in the silent corticotroph group (13 CT, 14 MRI and one air encephalogram) revealed 68% Grade 2 and 32% Grade 3 adenomas.RESULTS The recurrence rate in the ACTH immunopositive tumours was 32% at a mean of 5.8 years (range 1-16 years) which was not significantly different from the 33% recurrence rate previously recorded in the ACTH immunonegative tumours (P = 0.9). Two of the patients with silent corticotroph adenomas have suffered multiple recurrences; one patient has had three operations and two courses of radiotherapy for two episodes of recurrence and one patient has had four operations, two courses of radiotherapy and gamma knife therapy after three recurrences in total. In contrast, no patient with an ACTH immunonegative tumour has required more than one course of treatment for tumour regrowth.CONCLUSIONS This is the first single-centre comparative study of a series of clinically silent ACTH immunopositive tumours and has demonstrated that although they do not recur more often than ACTH immunonegative tumours, when they do regrow they show a more aggressive course. The practical implication of this is that there is no evidence for different postoperative imaging and radiotherapy protocols for ACTH immunopositive and immunonegative NFAs at initial presentation. However, if regrowth of a silent corticotroph tumour does occur then very careful monitoring is essential, after further treatment.