Góth Miklós, Hubina Erika, Kovács László, Szabolcs István
Orv Hetil. 2002 May 12;143(19 Suppl):1057-62.
The primary aim of therapy should be to remove symptoms, reduce tumor bulk, prevent relapse, and improve long-term outcome. Surgery, radiotherapy and medical therapies are used to achieve these aims. Post-treatment mean "safe" serum growth hormone values of < 2.5 ng/ml should be the therapeutic goal. Transsphenoidal surgery remains the first line treatment for acromegaly. Patients with microadenoma can expect 85%, while those with macroadenoma 50% chance to achieve safe serum growth hormone levels. Less than 20% of acromegalics respond to treatment with bromocriptine, while quinagolide and cabergoline may show better clinical response; the success rate is higher for tumors secreting both growth hormone and prolactin. Dopamine agonists may be considered either in combination with somatostatin-analogues or as monotherapy in selected patients, and in those with co-secretion of prolactin. Octreotide (Sandostatin, Novartis) is a synthetic somatostatin-analogue, which is administered subcutaneously in doses between 100 and 250 micrograms 3 times daily. Long-acting octreotide (Sandostatin LAR, Novartis) contains octreotide incorporated into microspheres of biodegradable polymer. To effectively lower serum growth hormone levels, monthly injections of 10-30 mg of long-acting octreotide are needed, serum growth hormone falls to 2.5 ng/ml in 70% of cases, and serum insulin-like growth factor I normalizes in 67%. Slow release lanreotide (Somatuline SR, Ipsen) is an alternative depot long-acting somatostatin-analogue, which is administered in a dose of 30 mg intramuscularly every 14, 10 or 7 days. Both compounds are equally, if not more, effective than subcutaneous octreotide, and significantly improve patient compliance. Pegvisomant (Sensus Drug Development Corporation) is a genetically engineered growth hormone receptor antagonist, which inhibits growth hormone action. When given subcutaneously in a dose of 20 mg/day, serum insulin-like growth factor I levels return to normal in 90% of patients. Theoretical concerns of tumor expansion have not been a problem to date, but long term studies are needed. Primary medical--somatostatin-analogue--therapy is recommended if surgery fails, if the patient refuses or unsuited for surgery and it may be also considered in patients with macroadenoma with extra--but not suprasellar extension, since the surgical "cure" rates of these tumors are low.
治疗的主要目标应是消除症状、缩小肿瘤体积、预防复发并改善长期预后。手术、放疗和药物治疗用于实现这些目标。治疗后血清生长激素的“安全”平均值<2.5 ng/ml应作为治疗目标。经蝶窦手术仍然是肢端肥大症的一线治疗方法。微腺瘤患者达到安全血清生长激素水平的几率为85%,而大腺瘤患者为50%。不到20%的肢端肥大症患者对溴隐亭治疗有反应,而喹高利特和卡麦角林可能显示出更好的临床反应;对于同时分泌生长激素和催乳素的肿瘤,成功率更高。多巴胺激动剂可与生长抑素类似物联合使用,或在特定患者中作为单一疗法使用,以及用于那些同时分泌催乳素的患者。奥曲肽(善宁,诺华公司)是一种合成的生长抑素类似物,皮下注射剂量为100至250微克,每日3次。长效奥曲肽(长效善宁,诺华公司)含有包裹在可生物降解聚合物微球中的奥曲肽。为有效降低血清生长激素水平,需要每月注射10 - 30毫克长效奥曲肽,70%的患者血清生长激素可降至2.5 ng/ml,67%的患者血清胰岛素样生长因子I恢复正常。缓释兰瑞肽(索马杜林SR,益普生公司)是另一种长效生长抑素类似物,每14、10或7天肌肉注射30毫克。这两种化合物即使不比皮下注射奥曲肽更有效,也同样有效,并且显著提高了患者的依从性。培维索孟(森苏斯药物开发公司)是一种基因工程生长激素受体拮抗剂,可抑制生长激素的作用。每日皮下注射20毫克时,90%的患者血清胰岛素样生长因子I水平恢复正常。目前,肿瘤扩大的理论担忧尚未成为问题,但仍需要长期研究。如果手术失败、患者拒绝手术或不适合手术,以及对于具有鞍外但非鞍上扩展的大腺瘤患者,由于这些肿瘤的手术“治愈率”较低,推荐采用以生长抑素类似物为主的初始药物治疗。