Macimorelin (AEZS-130)-Stimulated Growth Hormone (GH) Test: Validation of a Novel Oral Stimulation Test for the Diagnosis of Adult GH Deficiency
Macimorelin (AEZS-130)-Stimulated Growth Hormone (GH) Test: Validation of a Novel Oral Stimulation Test for the Diagnosis of Adult GH Deficiency
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DOI：
10.1210/jc.2013-1157
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发表时间：
2013-06-01
影响因子：
5.8
通讯作者：
Merriam, G. R.
中科院分区：
文献类型：
--
作者：
Garcia, J. M.;Swerdloff, R.;Merriam, G. R.
内容：在没有全垂体功能减退和低血清IGF-I水平的情况下，成人GH缺乏症（AGHD）的诊断需要GH刺激试验的确认。Macimorelin是一种新的，口服活性生长激素释放肽模拟物，刺激GH secretory.Objective：本研究的目的是确定的诊断疗效和安全性Macimorelin AGHD.Design：这是一个多中心的开放标签研究比较诊断准确性口服Macimorelin与精氨酸+GHRH AGHD患者和健康，匹配的控制。在对43名AGHD患者和10名对照进行测试后，GHRH类似物Geref诊断[GHRH（1-29）NH 2]在美国变得不可用。该研究是通过测试10个额外的AGHD患者和38个对照组与macimorelin单独完成的。主要结果Measure：峰GH面积后macimorelin的受试者工作特征曲线measured.Results：50 AGHD受试者和48个对照组进行了评价。接受马西莫瑞林治疗后，AGHD患者和对照组的峰值GH水平分别为2.36 +/- 5.69和17.71 +/- 19.11 ng/mL（P < .0001）。对于Macimorelin，受试者工作特征分析得出最佳GH临界点为2.7 ng/mL，敏感性为82%，特异性为92%，错误分类率为13%。对于接受这两种测试的受试者，马西莫林显示出与精氨酸+GHRH相当的辨别力（分别为0.99 vs 0.94，P = 0.29）。58%的受试者存在肥胖（体重指数> 30 kg/m2），对照组GH峰值水平与体重指数呈负相关（r =-0.37，P = .01）。使用非肥胖受试者6.8 ng/mL和肥胖受试者2.7 ng/mL的单独临界点将错误分类率降低至11%。只有1药物相关的严重不良事件，无症状的QT间期延长的心电图，reported.Conclusion：口服马西莫林是安全的，方便的，有效的诊断AGHD的准确性与精氨酸+GHRH测试相媲美。
Context: In the absence of panhypopituitarism and low serum IGF-I levels, the diagnosis of adult GH deficiency (AGHD) requires confirmation with a GH stimulation test. Macimorelin is a novel, orally active ghrelin mimetic that stimulates GH secretion.Objective: The objective of the study was to determine the diagnostic efficacy and safety of macimorelin in AGHD.Design: This was a multicenter open-label study comparing the diagnostic accuracy of oral macimorelin with that of arginine+GHRH in AGHD patients and healthy, matched controls. After 43 AGHD patients and 10 controls were tested, the GHRH analog Geref Diagnostic [GHRH(1-29) NH2] became unavailable in the United States. The study was completed by testing 10 additional AGHD patients and 38 controls with macimorelin alone.Main Outcome Measure: Peak GH area under the receiver operating characteristic curve after macimorelin was measured.Results: Fifty AGHD subjects and 48 controls were evaluated. Peak GH levels in AGHD patients and controls after macimorelin were 2.36 +/- 5.69 and 17.71 +/- 19.11 ng/mL, respectively (P < .0001). With macimorelin, the receiver operating characteristic analysis yielded an optimal GH cut point of 2.7 ng/mL, with82% sensitivity, 92% specificity, and13% misclassification rate. For subjects receiving both tests, macimorelin showed discrimination comparable with arginine+GHRH (area under the receiver operating characteristic curve 0.99 vs 0.94, respectively, P = .29). Obesity (body mass index > 30 kg/m(2)) was present in 58% of subjects, and peak GH levels were inversely associated with body mass index in controls (r = -0.37, P = .01). Using the separate cut points of 6.8 ng/mL for nonobese and 2.7 for obese subjects reduced the misclassification rate to 11%. Only 1 drug-related serious adverse event, an asymptomatic QT interval prolongation on the electrocardiogram, was reported.Conclusion: Oral macimorelin is safe, convenient, and effective in diagnosing AGHD with accuracy comparable with the arginine+GHRH test.