van der Hoek Joost, de Herder Wouter W, Feelders Richard A, van der Lely Aart-Jan, Uitterlinden Piet, Boerlin Viktor, Bruns Christian, Poon Kwai W, Lewis Ian, Weckbecker Gisbert, Krahnke Tillmann, Hofland Leo J, Lamberts Steven W
Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 2004 Feb;89(2):638-45. doi: 10.1210/jc.2003-031052.
Treatment with the somatostatin receptor (sst) subtype 2 predominant analogs octreotide and lanreotide induces clinical and biochemical cure in approximately 65% of acromegalic patients. GH-secreting pituitary adenomas, which are not controlled, also express sst(5). We compared the acute effects of octreotide and SOM230, a new somatostatin analog with high affinity for sst(1,2,3,5) on hormone release in acromegalic patients. In a single-dose, proof-of-concept study, 100 microg octreotide and 100 and 250 microg SOM230 were given s.c. to 12 patients with active acromegaly. Doses of 100 and 250 microg SOM230 dose-dependently suppressed GH levels from 2-8 h after administration (-38 +/- 7.7 vs. -61 +/- 6.7%, respectively; P < 0.01). A comparable suppression of GH levels by octreotide and 250 microg SOM230 was observed in eight patients (-65 +/- 7 vs. -72 +/- 7%, respectively). In three patients, the acute GH-lowering effect of 250 microg SOM230 was significantly superior to that of octreotide (-70 +/- 2 vs. -17 +/- 15%, respectively; P < 0.01). In one patient, the GH-lowering effect of octreotide was better than that of SOM230. Tolerability for SOM230 was good. Glucose levels were initially slightly elevated after octreotide and SOM230, compared with control day, whereas insulin levels were only significantly suppressed by octreotide. We conclude that SOM230 is an effective GH-lowering drug in acromegalic patients with the potential to increase the number of patients controlled during long-term medical treatment.
使用以生长抑素受体(sst)2亚型为主的类似物奥曲肽和兰瑞肽治疗,可使约65%的肢端肥大症患者实现临床和生化治愈。未得到控制的生长激素分泌型垂体腺瘤也表达sst(5)。我们比较了奥曲肽和SOM230(一种对sst(1,2,3,5)具有高亲和力的新型生长抑素类似物)对肢端肥大症患者激素释放的急性影响。在一项单剂量概念验证研究中,对12例活动性肢端肥大症患者皮下注射100微克奥曲肽以及100微克和250微克SOM230。给予100微克和250微克SOM230后2至8小时,剂量依赖性地抑制生长激素水平(分别为-38±7.7%和-61±6.7%;P<0.01)。8例患者中观察到奥曲肽和250微克SOM230对生长激素水平的抑制作用相当(分别为-65±7%和-72±7%)。3例患者中,250微克SOM230的急性降低生长激素作用显著优于奥曲肽(分别为-70±2%和-17±15%;P<0.01)。1例患者中,奥曲肽的降低生长激素作用优于SOM230。SOM230的耐受性良好。与对照日相比,奥曲肽和SOM230给药后血糖水平最初略有升高,而胰岛素水平仅被奥曲肽显著抑制。我们得出结论,SOM230是一种对肢端肥大症患者有效的降低生长激素药物,有可能增加长期药物治疗中得到控制的患者数量。