Paisley Angela N, Trainer Peter J
Department of Endocrinology, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK.
Curr Opin Pharmacol. 2003 Dec;3(6):672-7. doi: 10.1016/j.coph.2003.07.007.
Acromegaly is a rare disabling disorder that results in premature death. The excess mortality and morbidity are the result of prolonged elevation of growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels, and vigorous control of these improves well-being and restores life expectancy to normal. Recognition of the benefits of treatment has emphasised the need for optimal control of the GH/IGF-I axis. Transsphenoidal surgery is first-line therapy in the majority of patients; however, as most tumours are macroadenomas, cure rates are low. The role of radiotherapy is evolving and, although extremely effective at controlling tumour growth, it can take up to 15 years to control GH & IGF-I levels. In the interim, medical therapy is necessary. Dopamine agonists are inexpensive oral agents but, although most patients experience some benefit, GH and IGF-I levels are only normalised in around 35-40% of patients, and side effects are common. Somatostatin analogues are the gold standard of medical treatment. They can induce tumour shrinkage in a proportion of patients and can normalise the GH/IGF-I axis (at best) in approximately 65% of individuals; however, this leaves a significant cohort uncontrolled. The advent of the GH receptor antagonist pegvisomant provides the potential for IGF-I to be normalised in virtually every patient, but this novel form of therapy, which does not act on the pituitary, also raises many questions.
肢端肥大症是一种罕见的致残性疾病,可导致过早死亡。过高的死亡率和发病率是生长激素(GH)和胰岛素样生长因子-I(IGF-I)水平长期升高的结果,积极控制这些指标可改善健康状况并使预期寿命恢复正常。对治疗益处的认识强调了对GH/IGF-I轴进行最佳控制的必要性。经蝶窦手术是大多数患者的一线治疗方法;然而,由于大多数肿瘤是大腺瘤,治愈率较低。放射治疗的作用正在不断演变,虽然它在控制肿瘤生长方面极其有效,但控制GH和IGF-I水平可能需要长达15年的时间。在此期间,药物治疗是必要的。多巴胺激动剂是便宜的口服药物,虽然大多数患者会有一些益处,但只有约35-40%的患者的GH和IGF-I水平可恢复正常,且副作用常见。生长抑素类似物是药物治疗的金标准。它们可使一部分患者的肿瘤缩小,并使约65%的个体的GH/IGF-I轴(最佳情况下)恢复正常;然而,仍有相当一部分患者无法得到控制。GH受体拮抗剂培维索孟的出现为几乎每位患者的IGF-I恢复正常提供了可能,但这种不作用于垂体的新型治疗方法也引发了许多问题。