Kiseljak-Vassiliades Katja, Carlson Nichole E, Borges Manuel T, Kleinschmidt-DeMasters B K, Lillehei Kevin O, Kerr Janice M, Wierman Margaret E
Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, 12801 East 17th Ave, RC1 South Room 7402A, Aurora, CO, 80045, USA,
Endocrine. 2015 May;49(1):231-41. doi: 10.1007/s12020-014-0383-y. Epub 2014 Aug 17.
Growth hormone (GH) pituitary tumors are associated with significant morbidity and mortality. Current treatments, including surgery and medical therapy with somatostatin analogs (SSA), dopamine agonists and/or a GH receptor antagonist, result in disease remission in approximately half of patients. Predictors of GH tumor response to different therapies have been incompletely defined based on histologic subtype, particularly densely (DG) versus sparsely (SG) granulated adenomas. The aim of this study was to examine our own institutional experience with GH adenomas and correlate how subtype related to clinical parameters as well as response to surgery and medical therapies. A retrospective chart review of 101 acromegalic patients operated by a single neurosurgeon was performed. Clinical data were correlated with histologic subtype and disease control, as defined by IGF-1 levels, and random growth hormone levels in response to surgery and/or medical therapies. SG tumors, compared to DG, occurred in younger patients (p = 0.0010), were 3-fold larger (p = 0.0030) but showed no differences in tumor-invasion characteristics (p = 0.12). DG tumors had a higher rate of remission in response to surgery compared to SG, 65.7 vs. 14.3 % (p < 0.0001), as well as to medical therapy with SSAs (68.8 % for DG vs. 28.6 % for SG tumors; p = 0.028). SG tumors not controlled with SSAs consistently responded to a switch to, or addition of, a GH receptor antagonist. Histological GH tumor subtyping implicates a different clinical phenotype and biologic behavior, and provides prognostic significance for surgical success and response to medical therapies.
生长激素(GH)垂体瘤与显著的发病率和死亡率相关。目前的治疗方法,包括手术以及使用生长抑素类似物(SSA)、多巴胺激动剂和/或生长激素受体拮抗剂的药物治疗,约半数患者可实现疾病缓解。基于组织学亚型,尤其是致密颗粒型(DG)与稀疏颗粒型(SG)腺瘤,GH肿瘤对不同治疗反应的预测指标尚未完全明确。本研究的目的是考察我们自己机构对GH腺瘤的治疗经验,并关联亚型与临床参数以及手术和药物治疗反应之间的关系。对由一名神经外科医生实施手术的101例肢端肥大症患者进行了回顾性病历审查。临床数据与组织学亚型及疾病控制情况相关,疾病控制情况由IGF-1水平以及手术和/或药物治疗后的随机生长激素水平定义。与DG肿瘤相比,SG肿瘤发生于更年轻的患者(p = 0.0010),体积大三倍(p = 0.0030),但在肿瘤侵袭特征方面无差异(p = 0.12)。与SG肿瘤相比,DG肿瘤对手术的缓解率更高,分别为65.7%和14.3%(p < 0.0001),对SSA药物治疗的缓解率也更高(DG肿瘤为68.8%,SG肿瘤为28.6%;p = 0.028)。未被SSA控制的SG肿瘤持续对改用或加用生长激素受体拮抗剂有反应。组织学GH肿瘤亚型划分意味着不同的临床表型和生物学行为,并为手术成功率和药物治疗反应提供预后意义。