Endocr Pract. 2019 Apr;25(4):379-393. doi: 10.4158/EP-2018-0500. Epub 2019 Jan 18.
To clarify the selection of medical therapy following transsphenoidal surgery in patients with acromegaly, based on growth hormone (GH)/insulin-like growth factor 1 (IGF-1) response and glucometabolic control. We carried out a systematic literature review on three of the best studied and most practical predictive markers of the response to somatostatin analogues (SSAs): somatostatin receptor (SSTR) expression, tumor morphologic classification, and T2-weighted magnetic resonance imaging (MRI) signal intensity. Additional analyses focused on glucose metabolism in treated patients. The literature survey confirmed significant associations of all three factors with SSA responsiveness. SSTR expression appears necessary for the SSA response; however, it is not sufficient, as approximately half of SSTR2-positive tumors failed to respond clinically to first-generation SSAs. MRI findings (T2-hypo-intensity) and a densely granulated phenotype also correlate with SSA efficacy, and are advantageous as predictive markers relative to SSTR expression alone. Glucometabolic control declines with SSA monotherapy, whereas GH receptor antagonist (GHRA) monotherapy may restore normoglycemia. We propose a decision tree to guide selection among SSAs, dopamine agonists (DAs), and GHRA for medical treatment of acromegaly in the postsurgical setting. This decision tree employs three validated predictive markers and other clinical considerations, to determine whether SSAs are appropriate first-line medical therapy in the postsurgical setting. DA treatment is favored in patients with modest IGF-1 elevation. GHRA treatment should be considered for patients with T2-hyperintense tumors with a sparsely granulated phenotype and/or low SSTR2 staining, and may also be favored for individuals with diabetes. Prospective analyses are required to test the utility of this therapeutic paradigm. = dopamine agonist; = densely granulated; = growth hormone; = growth hormone receptor antagonist; = glycated hemoglobin; = insulin-like growth factor-1; = magnetic resonance imaging; = sparsely granulated; = somatostatin analogue; = somatostatin receptor.
为了明确肢端肥大症患者经蝶窦手术后的医学治疗选择，基于生长激素（GH）/胰岛素样生长因子 1（IGF-1）反应和糖代谢控制情况。我们对三种最具研究价值和实用性的生长抑素类似物（SSA）反应预测标志物进行了系统的文献回顾：生长抑素受体（SSTR）表达、肿瘤形态学分类和 T2 加权磁共振成像（MRI）信号强度。此外，还对治疗患者的葡萄糖代谢进行了分析。文献综述证实了所有三种因素与 SSA 反应性显著相关。SSTR 表达对于 SSA 反应是必要的，但这还不够，因为大约一半的 SSTR2 阳性肿瘤在第一代 SSA 治疗中未能产生临床反应。MRI 结果（T2 低信号）和致密颗粒状表型也与 SSA 疗效相关，作为预测标志物优于单独的 SSTR 表达。SSA 单药治疗可导致糖代谢紊乱，而 GH 受体拮抗剂（GHRA）单药治疗可能恢复正常血糖。我们提出了一个决策树，以指导在术后环境中选择 SSA、多巴胺激动剂（DA）和 GHRA 进行肢端肥大症的药物治疗。该决策树采用了三个经过验证的预测标志物和其他临床考虑因素，以确定 SSA 是否适合作为术后环境中的一线药物治疗。DA 治疗适用于 IGF-1 中度升高的患者。对于 T2 高信号、稀疏颗粒状表型和/或低 SSTR2 染色的肿瘤患者，应考虑使用 GHRA 治疗，对于有糖尿病的个体，也可能首选 GHRA 治疗。需要进行前瞻性分析来测试这种治疗模式的实用性。 = 多巴胺激动剂；= 致密颗粒状；= 生长激素；= 生长激素受体拮抗剂；= 糖化血红蛋白；= 胰岛素样生长因子-1；= 磁共振成像；= 稀疏颗粒状；= 生长抑素类似物；= 生长抑素受体。
