Department of Internal Medicine, Erasmus University MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Eur J Endocrinol. 2011 Jan;164(1):11-6. doi: 10.1530/EJE-10-0969. Epub 2010 Nov 2.
Medical treatment of acromegaly with long-acting somatostatin analogs (LA-SMSA) and the GH receptor antagonist, pegvisomant (PEGV), has made it possible to achieve normal serum IGF1 concentrations in a majority of patients with acromegaly. These two compounds, however, impact the GH-IGF1 axis differently, which challenges the traditional biochemical assessment of the therapeutic response. We postulate that LA-SMSA in certain patients normalizes serum IGF1 levels in the presence of elevated GH actions in extra-hepatic tissues. This may result in persistent disease activity for which we propose the term extra-hepatic acromegaly. PEGV, on the other hand, blocks systemic GH actions, which are not necessarily reliably reflected by serum IGF1 levels, and this treatment causes a further elevation of serum GH levels. Medical treatment is therefore difficult to monitor with the traditional biomarkers. Moreover, the different modes of actions of LA-SMSA and PEGV make it attractive to use the two drugs in combination. We believe that it is time to challenge the existing concepts of treatment and monitoring of patients with acromegaly.
使用长效生长抑素类似物（LA-SMSA）和生长激素受体拮抗剂培维索孟（PEGV）治疗肢端肥大症，使大多数肢端肥大症患者的血清 IGF1 浓度恢复正常。然而，这两种化合物对 GH-IGF1 轴的影响不同，这对治疗反应的传统生化评估提出了挑战。我们假设，在某些患者中，LA-SMSA 在肝脏外组织中 GH 作用升高的情况下使血清 IGF1 水平正常化。这可能导致持续的疾病活动，我们称之为肝外肢端肥大症。另一方面，PEGV 阻断全身 GH 作用，而血清 IGF1 水平不一定可靠地反映这些作用，这种治疗会进一步升高血清 GH 水平。因此，传统的生物标志物很难监测药物治疗。此外，LA-SMSA 和 PEGV 的不同作用模式使得联合使用这两种药物具有吸引力。我们认为，现在是时候挑战现有的肢端肥大症患者的治疗和监测概念了。
