Cordeiro Diogo, Xu Zhiyuan, Mehta Gautam U, Ding Dale, Vance Mary Lee, Kano Hideyuki, Sisterson Nathaniel, Yang Huai-Che, Kondziolka Douglas, Lunsford L Dade, Mathieu David, Barnett Gene H, Chiang Veronica, Lee John, Sneed Penny, Su Yan-Hua, Lee Cheng-Chia, Krsek Michal, Liscak Roman, Nabeel Ahmed M, El-Shehaby Amr, Abdel Karim Khaled, Reda Wael A, Martinez-Moreno Nuria, Martinez-Alvarez Roberto, Blas Kevin, Grills Inga, Lee Kuei C, Kosak Mikulas, Cifarelli Christopher P, Katsevman Gennadiy A, Sheehan Jason P
1Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia.
2Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
J Neurosurg. 2018 Nov 9;131(4):1188-1196. doi: 10.3171/2018.5.JNS18509. Print 2019 Oct 1.
Recurrent or residual adenomas are frequently treated with Gamma Knife radiosurgery (GKRS). The most common complication after GKRS for pituitary adenomas is hypopituitarism. In the current study, the authors detail the timing and types of hypopituitarism in a multicenter, international cohort of pituitary adenoma patients treated with GKRS.
Seventeen institutions pooled clinical data obtained from pituitary adenoma patients who were treated with GKRS from 1988 to 2016. Patients who had undergone prior radiotherapy were excluded. A total of 1023 patients met the study inclusion criteria. The treated lesions included 410 nonfunctioning pituitary adenomas (NFPAs), 262 cases of Cushing's disease (CD), and 251 cases of acromegaly. The median follow-up was 51 months (range 6-246 months). Statistical analysis was performed using a Cox proportional hazards model to evaluate factors associated with the development of new-onset hypopituitarism.
At last follow-up, 248 patients had developed new pituitary hormone deficiency (86 with NFPA, 66 with CD, and 96 with acromegaly). Among these patients, 150 (60.5%) had single and 98 (39.5%) had multiple hormone deficiencies. New hormonal changes included 82 cortisol (21.6%), 135 thyrotropin (35.6%), 92 gonadotropin (24.3%), 59 growth hormone (15.6%), and 11 vasopressin (2.9%) deficiencies. The actuarial 1-year, 3-year, 5-year, 7-year, and 10-year rates of hypopituitarism were 7.8%, 16.2%, 22.4%, 27.5%, and 31.3%, respectively. The median time to hypopituitarism onset was 39 months.In univariate analyses, an increased rate of new-onset hypopituitarism was significantly associated with a lower isodose line (p = 0.006, HR = 8.695), whole sellar targeting (p = 0.033, HR = 1.452), and treatment of a functional pituitary adenoma as compared with an NFPA (p = 0.008, HR = 1.510). In multivariate analyses, only a lower isodose line was found to be an independent predictor of new-onset hypopituitarism (p = 0.001, HR = 1.38).
Hypopituitarism remains the most common unintended effect of GKRS for a pituitary adenoma. Treating the target volume at an isodose line of 50% or greater and avoiding whole-sellar radiosurgery, unless necessary, will likely mitigate the risk of post-GKRS hypopituitarism. Follow-up of these patients is required to detect and treat latent endocrinopathies.
复发性或残留性腺瘤常采用伽玛刀放射外科治疗（GKRS）。垂体腺瘤GKRS术后最常见的并发症是垂体功能减退。在本研究中，作者详细阐述了接受GKRS治疗的垂体腺瘤患者多中心国际队列中垂体功能减退的发生时间和类型。
17家机构汇总了1988年至2016年接受GKRS治疗的垂体腺瘤患者的临床数据。排除既往接受过放疗的患者。共有1023例患者符合研究纳入标准。治疗的病变包括410例无功能垂体腺瘤（NFPA）、262例库欣病（CD）和251例肢端肥大症。中位随访时间为51个月（范围6 - 246个月）。采用Cox比例风险模型进行统计分析，以评估与新发垂体功能减退发生相关的因素。
在最后一次随访时，248例患者出现了新的垂体激素缺乏（NFPA患者86例，CD患者66例，肢端肥大症患者96例）。在这些患者中，150例（60.5%）为单一激素缺乏，98例（39.5%）为多种激素缺乏。新出现的激素变化包括82例皮质醇缺乏（21.6%）、135例促甲状腺激素缺乏（35.6%）、92例促性腺激素缺乏（24.3%）、59例生长激素缺乏（15.6%）和11例血管加压素缺乏（2.9%）。垂体功能减退的1年、3年、5年、7年和10年精算发生率分别为7.8%、16.2%、22.4%、27.5%和31.3%。垂体功能减退发病的中位时间为39个月。在单因素分析中，新发垂体功能减退发生率增加与较低的等剂量线显著相关（p = 0.006，HR = 8.695）、全鞍区靶向照射（p = 0.033，HR = 1.452）以及与NFPA相比功能性垂体腺瘤的治疗（p = 0.008，HR = 1.510）。在多因素分析中，仅较低的等剂量线被发现是新发垂体功能减退的独立预测因素（p = 0.001，HR = 1.38）。
垂体功能减退仍然是垂体腺瘤GKRS最常见的意外效应。将靶区体积治疗在50%或更高的等剂量线上，并避免全鞍区放射外科治疗（除非必要），可能会降低GKRS术后垂体功能减退的风险。需要对这些患者进行随访，以检测和治疗潜在的内分泌疾病。
