Biermasz Nienke R, Pereira Alberto M, Smit Jan W A, Romijn Johannes A, Roelfsema Ferdinand
Department of Metabolism and Endocrinology, Leiden University Medical Centre, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Growth Horm IGF Res. 2005 Jun;15(3):200-6. doi: 10.1016/j.ghir.2005.02.007.
Depot formulations of somatostatin analogues are increasingly used in the treatment of active acromegaly. A priori knowledge of the efficacy of these drugs in controlling GH excess is clinically relevant, because only approximately 60% of the patients respond with adequate control of GH (GH levels < 5 mU/L) and/or IGF-1 levels upon this treatment. Therefore, we assessed the acute responses of serum GH levels to a new octreotide test (intravenous administration of 50 microg) in 98 consecutive patients with active acromegaly and we measured the predictive value of this test for the efficacy of chronic octreotide-long acting repeatable (octreotide-LAR) treatment in 18 patients.
Serum GH concentrations were measured before and at 20, 30, 45, 60, 90, 120, 150 and 180 min following 50 microg i.v. octreotide. The minimal achieved GH was used for analysis. Octreotide-LAR was individually titrated aiming at a normal serum IGF-I for age and a serum GH < 5 mU/L. The mean of 3-6 monthly serum GH and IGF-I measurements after individual dose adjustment was used for evaluating the efficacy of chronic therapy.
Octreotide decreased GH levels to values below 5 mU/L in only 49% of unselected consecutive patients and the response was inversely related to basal GH levels. In patients with baseline GH above 50 mU/L, 50 microg i.v. octreotide reduced GH to < 5 mU/L in only 15% of cases (n = 41), whereas in patients with baseline GH levels below 50 mU/L this goal was achieved in 77% of cases. The fractional decrease in GH levels upon octreotide injection was similar in microadenomas and macroadenomas. The minimally achieved serum GH concentration during the intravenous octreotide test was a good predictor for the GH concentrations during long-term octreotide-LAR treatment as assessed in 18 patients. The intravenous octreotide test, using a minimal GH level of < 5 mU/L, had a sensitivity, positive and negative predictive value of 100% for prediction of GH suppression to below 5 mU/L during long term octreotide-LAR treatment. For predicting the response of IGF-I during long-term treatment, the test performed with a sensitivity of 73% and a positive predictive value of 73%.
Intravenous octreotide reduces GH to concentrations < 5 mU/L in approximately 50% of consecutive patients with active acromegaly, which predicts a good response to chronic octreotide-LAR treatment.
生长抑素类似物的长效剂型越来越多地用于治疗活动期肢端肥大症。了解这些药物控制生长激素（GH）过量的疗效的先验知识具有临床相关性，因为在此治疗中只有约60%的患者能充分控制GH（GH水平<5 mU/L）和/或胰岛素样生长因子-1（IGF-1）水平。因此，我们评估了98例连续的活动期肢端肥大症患者血清GH水平对一种新的奥曲肽试验（静脉注射50微克）的急性反应，并测量了该试验对18例患者慢性奥曲肽长效可重复注射（奥曲肽-LAR）治疗疗效的预测价值。
在静脉注射50微克奥曲肽前及注射后20、30、45、60、90、120、150和180分钟测量血清GH浓度。将达到的最低GH用于分析。奥曲肽-LAR根据年龄的正常血清IGF-I和血清GH<5 mU/L进行个体化滴定。在个体剂量调整后3至6个月的血清GH和IGF-I测量平均值用于评估慢性治疗的疗效。
在未选择的连续患者中，奥曲肽仅使49%的患者GH水平降至5 mU/L以下，且反应与基础GH水平呈负相关。在基线GH高于50 mU/L的患者中，静脉注射50微克奥曲肽仅使15%的病例（n = 41）的GH降至<5 mU/L，而在基线GH水平低于50 mU/L的患者中，77%的病例达到了这一目标。微腺瘤和大腺瘤患者注射奥曲肽后GH水平的下降分数相似。在18例患者中评估发现，静脉注射奥曲肽试验期间达到的最低血清GH浓度是长期奥曲肽-LAR治疗期间GH浓度的良好预测指标。使用最低GH水平<5 mU/L的静脉注射奥曲肽试验，对长期奥曲肽-LAR治疗期间GH抑制至<5 mU/L的预测敏感性、阳性预测值和阴性预测值均为100%。对于预测长期治疗期间IGF-I的反应，该试验的敏感性为73%，阳性预测值为73%。
静脉注射奥曲肽可使约50%的连续活动期肢端肥大症患者的GH浓度降至<5 mU/L，这预示着对慢性奥曲肽-LAR治疗有良好反应。
