Franck Sanne E, van der Lely Aart Jan, Neggers Sebastian
Department of Internal Medicine, Erasmus University MC, Rotterdam, the Netherlands.
Eur Endocrinol. 2013 Mar;9(1):66-70. doi: 10.17925/EE.2013.09.01.66. Epub 2013 Mar 15.
After the introduction of somatostatin analogs (LA-SMSA) and the growth hormone (GH) receptor antagonist, pegvisomant (Peg-v) normal serum insulin-like growth factor-1 (IGF-1) concentrations in virtually every patients with acromegaly is possible. The impact of these products on the GH-IGF1 axis is completely different. We advocate that LA-SMSA may normalize serum IGF1 levels in the presence of elevated GH actions in extra-hepatic tissues. This results in persistent peripheral disease activity that we call 'extra-hepatic acromegaly'. Peg-v competitively blocks systemic GH action and results in a GH serum level increase. Therefore high doses of Peg-v are necessary to control IGF-1. Since the mode of action differs between these products, it is questionable if identical IGF-1 levels, during Peg-v or LA-SMSA are really identical representations of the biochemical situation. With the traditional biomarkers medical treatment is therefore difficult to monitor with the traditional biomarkers. Additionally, Peg-v and LA-SMSA could be ideal combination since they have different mode of actions. We believe that the time has come to challenge the existing concepts of treatment and monitoring of patients with acromegaly.
在引入生长抑素类似物(长效生长抑素类似物,LA-SMSA)和生长激素(GH)受体拮抗剂培维索孟(Peg-v)后,几乎每个肢端肥大症患者的血清胰岛素样生长因子-1(IGF-1)浓度都有可能恢复正常。这些药物对GH-IGF1轴的影响完全不同。我们认为,在肝外组织中GH作用增强的情况下,LA-SMSA可能使血清IGF1水平恢复正常。这会导致持续的外周疾病活动,我们称之为“肝外肢端肥大症”。Peg-v竞争性阻断全身GH作用,导致GH血清水平升高。因此,需要高剂量的Peg-v来控制IGF-1。由于这些药物的作用方式不同,在使用Peg-v或LA-SMSA期间相同的IGF-1水平是否真的能代表相同的生化状况,这是值得怀疑的。因此,使用传统生物标志物很难对药物治疗进行监测。此外,Peg-v和LA-SMSA可能是理想的组合,因为它们的作用方式不同。我们认为,挑战肢端肥大症患者现有治疗和监测观念的时候已经到了。