Cohen-Inbar Or, Ramesh Arjun, Xu Zhiyuan, Vance Mary Lee, Schlesinger David, Sheehan Jason P
Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA.
Department of Medicine, University of Virginia, Charlottesville, VA, USA.
Clin Endocrinol (Oxf). 2016 Apr;84(4):524-31. doi: 10.1111/cen.12938. Epub 2015 Oct 5.
For patient with a recurrent or residual acromegaly or Cushing's disease (CD) after resection, gamma knife radiosurgery (GKRS) is often used. Hypopituitarism is the most common adverse effect after GKRS treatment. The paucity of studies with long-term follow-up has hampered understanding of the latent risks of hypopituitarism in patients with acromegaly or CD. We report the long-term risks of hypopituitarism for patients treated with GKRS for acromegaly or CD.
From a prospectively created, IRB-approved database, we identified all patients with acromegaly or CD treated with GKRS at the University of Virginia from 1989 to 2008. Only patients with a minimum endocrine follow-up of 60 months were included. The median follow-up is 159·5 months (60·1-278). Thorough radiological and endocrine assessments were performed immediately before GKRS and at regular follow-up intervals. New onset of hypopituitarism was defined as pituitary hormone deficits after GKRS requiring corresponding hormone replacement.
Sixty patients with either acromegaly or CD were included. Median tumour volume at time of GKRS was 1·3 cm(3) (0·3-13·4), and median margin dose was 25 Gy (6-30). GKRS-induced new pituitary deficiency occurred in 58·3% (n = 35) of patients. Growth hormone deficiency was most common (28·3%, n = 17). The actuarial overall rates of hypopituitarism at 3, 5 and 10 years were 10%, 21·7% and 53·3%, respectively. The median time to hypopituitarism was 61 months after GKRS (range, 12-160). Cavernous sinus invasion of the tumour was found to correlate with the occurrence of a new or progressive hypopituitarism after GKRS (P = 0·018).
Delayed hypopituitarism increases as a function of time after radiosurgery. Hormone axes appear to vary in terms of radiosensitivity. Patients with adenoma in the cavernous sinus are more prone to develop loss of pituitary function after GKRS.
对于切除术后复发或残留的肢端肥大症或库欣病(CD)患者,常采用伽玛刀放射外科治疗(GKRS)。垂体功能减退是GKRS治疗后最常见的不良反应。长期随访研究的匮乏阻碍了对肢端肥大症或CD患者垂体功能减退潜在风险的认识。我们报告了接受GKRS治疗的肢端肥大症或CD患者垂体功能减退的长期风险。
从一个前瞻性创建、经机构审查委员会批准的数据库中,我们确定了1989年至2008年在弗吉尼亚大学接受GKRS治疗的所有肢端肥大症或CD患者。仅纳入内分泌随访至少60个月的患者。中位随访时间为159.5个月(60.1 - 278个月)。在GKRS治疗前及定期随访时进行全面的放射学和内分泌评估。垂体功能减退的新发定义为GKRS治疗后出现垂体激素缺乏并需要相应的激素替代治疗。
纳入60例肢端肥大症或CD患者。GKRS治疗时肿瘤体积中位数为1.3 cm³(0.3 - 13.4),中位边缘剂量为25 Gy(6 - 30)。GKRS导致58.3%(n = 35)的患者出现新的垂体功能减退。生长激素缺乏最为常见(28.3%,n = 17)。3年、5年和10年垂体功能减退的精算总体发生率分别为10%、21.7%和53.3%。垂体功能减退的中位时间为GKRS治疗后61个月(范围,12 - 160个月)。发现肿瘤侵犯海绵窦与GKRS治疗后新的或进行性垂体功能减退的发生相关(P = 0.018)。
放射外科治疗后垂体功能减退的延迟发生率随时间增加。激素轴的放射敏感性似乎有所不同。海绵窦内有腺瘤的患者在GKRS治疗后更易发生垂体功能丧失。