Pieters G F, van Liessum P A, Smals A G, van Gennep J A, Benraad T J, Kloppenborg P W
Department of Medicine, St. Radboud Hospital, University of Nijmegen, The Netherlands.
Acta Endocrinol Suppl (Copenh). 1987;286:9-18.
Twelve patients with active acromegaly were treated with the long-acting somatostatin analogue SMS 201-995 (SMS), at a dose of 50 micrograms sc twice daily in the first 2 weeks of treatment and 100 micrograms sc thereafter. Four h after the first injection of SMS, GH levels became normal in 8 of the 12 patients. Basal glucose levels were significantly lower at the 28th day of treatment. This glucose lowering effect was stronger in the diabetic than in the nondiabetic patients. The postprandial rise of insulin levels was reversed by SMS, leading to a more pronounced postprandial rise of glucose, whereas the postprandial secretion of glucagon was also reversed by SMS. The rise of glucose levels during oral glucose loading was similar before and during SMS, despite a strong inhibitory effect of the drug on the insulin rise after glucose loading. Basal TSH levels were not influenced by SMS, the TRH-induced TSH response, however, was significantly blunted. Although the basal PRL levels were significantly reduced by SMS, the TRH-induced PRL rise was similar before and during administration of the analogue. Paradoxical GH responses to TRH disappeared in 7 out of 8 patients during SMS. Paradoxical GH responses to GnRH, however, persisted in 4 out of 4 patients. Paradoxical responses of GH after glucose loading disappeared in 2 out of 2 patients. The GH response after GHRH administration was strongly suppressed by SMS. During long-term treatment (up to 2 years), the GH level obtained within 5 h after the last injection of SMS remained normal in the patients whose GH levels normalized at the first day of treatment. There was a good response of the disease to this treatment, and no serious adverse reactions were observed. We conclude that SMS normalizes most anomalous growth hormone kinetics in acromegaly. The drug offers a new tool in the treatment of this disease.
12例活动期肢端肥大症患者接受长效生长抑素类似物SMS 201-995(SMS)治疗,治疗的前2周剂量为50微克皮下注射,每日2次,此后为100微克皮下注射。首次注射SMS 4小时后,12例患者中有8例的生长激素(GH)水平恢复正常。治疗第28天时基础血糖水平显著降低。这种降糖作用在糖尿病患者中比非糖尿病患者更强。SMS可逆转餐后胰岛素水平的升高,导致餐后血糖升高更明显,而SMS也可逆转餐后胰高血糖素的分泌。口服葡萄糖负荷试验期间血糖水平的升高在使用SMS前后相似,尽管该药物对葡萄糖负荷后胰岛素升高有强烈抑制作用。基础促甲状腺激素(TSH)水平不受SMS影响,然而,促甲状腺激素释放激素(TRH)诱导的TSH反应明显减弱。尽管基础催乳素(PRL)水平因SMS而显著降低,但TRH诱导的PRL升高在使用该类似物前后相似。8例患者中有7例在使用SMS期间对TRH的反常GH反应消失。然而,4例患者中有4例对促性腺激素释放激素(GnRH)的反常GH反应持续存在。2例患者中有2例葡萄糖负荷后GH的反常反应消失。生长激素释放激素(GHRH)给药后的GH反应被SMS强烈抑制。在长期治疗(长达2年)期间,治疗第一天GH水平恢复正常的患者在最后一次注射SMS后5小时内测得的GH水平仍保持正常。该疾病对这种治疗反应良好,未观察到严重不良反应。我们得出结论,SMS可使肢端肥大症中大多数异常的生长激素动力学恢复正常。该药物为治疗这种疾病提供了一种新工具。