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生长激素(GH)峰值与曲线下面积在成人GH缺乏症诊断中的比较:对GHRH + GHRP-6试验提供变量的分析

Growth hormone (GH) peaks versus areas under the curve in the diagnosis of adult GH deficiency: analysis of the variables provided by the GHRH + GHRP-6 test.

作者信息

Koppeschaar Hans P F, Popovic Vera, Leal Alfonso, Otero Xose L, Torres Elena, Paramo Concha, Micic Dragan, Garcia-Mayor Ricardo V, Sartorio Alessandro, Dieguez Carlos, Casanueva Felipe F

机构信息

Department of Endocrinology, University Medical Center Utrech, Utrech, The Netherlands.

出版信息

Pituitary. 2004;7(1):15-20. doi: 10.1023/b:pitu.0000044629.10484.40.

DOI:10.1023/b:pitu.0000044629.10484.40
PMID:15638293
Abstract

BACKGROUND

The diagnosis of growth hormone deficiency (GHD) relies on provocative tests of GH reserve. The aim in these tests is to obtain an objective, biochemical-based, measure of gland function, but clinicians and researchers rely on the GH peak, as a surrogate of the 24-hour pituitary secretion. However, on a mathematical basis the area under the secretory curve (AUC) should be more valid for this evaluation.

OBJECTIVES

To validate which variable provided by a provocative test of GH secretion is mathematically more robust for supporting the clinical diagnosis. Adult normal subjects and GHD patients were challenged with the combined stimulus GHRH + GHRP-6. The diagnostic efficacy of the GH peak, and the AUC were compared by the receiver operating characteristic (ROC) curve methodology.

PATIENTS AND METHODS

146 patients with GH deficiency due to organic pituitary disease and 184 healthy subjects were administered GHRH 1 microg/Kg iv, plus GHRP-6 1 microg/Kg iv, and GH was determined. Four variables were studied: (a) the GH peak; (b) the "standard" AUC, (c) the "stimulated" AUC and (d) the basal value, used as internal control.

RESULTS

Under ROC curve analysis, the basal variable was devoid of diagnostic capability, while the other variables performed strikingly well, the ROC curve area for the GH peak was 0.9997; and for the AUC 0.9993, with no statistical differences.

CONCLUSIONS

The variables provided by measuring the GH peak and the area under the curve were similarly effective for diagnosis, although on clinical grounds, the peak was more convenient as needed no calculation. If results for other test were similar the time-honored method of measuring the GH peak could be considered mathematically validated.

摘要

背景

生长激素缺乏症(GHD)的诊断依赖于生长激素储备的激发试验。这些试验的目的是获得基于生化指标的客观腺体功能测量值,但临床医生和研究人员依赖生长激素峰值作为24小时垂体分泌的替代指标。然而,从数学角度来看,分泌曲线下面积(AUC)在这种评估中应该更有效。

目的

验证生长激素分泌激发试验提供的哪个变量在数学上对支持临床诊断更可靠。成年正常受试者和生长激素缺乏症患者接受生长激素释放激素(GHRH)+生长激素释放肽-6(GHRP-6)联合刺激。通过受试者操作特征(ROC)曲线方法比较生长激素峰值和AUC的诊断效能。

患者和方法

对146例因器质性垂体疾病导致生长激素缺乏的患者和184例健康受试者静脉注射1μg/kg的GHRH加1μg/kg的GHRP-6,并测定生长激素水平。研究了四个变量:(a)生长激素峰值;(b)“标准”AUC;(c)“刺激后”AUC;(d)基础值,用作内部对照。

结果

在ROC曲线分析中,基础变量没有诊断能力,而其他变量表现出色,生长激素峰值的ROC曲线面积为0.9997;AUC的ROC曲线面积为0.9993,无统计学差异。

结论

测量生长激素峰值和曲线下面积所提供的变量在诊断方面同样有效,尽管从临床角度来看,峰值更方便,因为无需计算。如果其他试验结果相似,测量生长激素峰值这种历史悠久的方法在数学上可被认为是有效的。

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本文引用的文献

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Hypoglycemia: a potent stimulus to secretion of growth hormone.低血糖:生长激素分泌的有力刺激因素。
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A single growth hormone (GH) determination is sufficient for the diagnosis of GH-deficiency in adult patients using the growth hormone releasing hormone plus growth hormone releasing peptide-6 test.
对于成年患者,使用生长激素释放激素加生长激素释放肽-6试验时,单次生长激素(GH)测定足以诊断生长激素缺乏症。
Clin Endocrinol (Oxf). 2002 Sep;57(3):377-84. doi: 10.1046/j.1365-2265.2002.01623.x.
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Physical activity or food intake prior to testing did not affect the reproducibility of GH secretion elicited by GH releasing hormone plus GH-releasing hexapeptide in normal adult subjects.在正常成年受试者中,测试前的身体活动或食物摄入并不影响生长激素释放激素加生长激素释放六肽所引发的生长激素分泌的可重复性。
Clin Endocrinol (Oxf). 2002 Jan;56(1):89-94. doi: 10.1046/j.0300-0664.2001.01445.x.
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Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency?哪些患者在诊断成人生长激素缺乏症时不需要进行生长激素刺激试验?
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Growth Horm IGF Res. 2001 Jun;11(3):137-65. doi: 10.1054/ghir.2001.0203.
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Stimulated secretion of pituitary hormones in normal humans: a novel direct assessment from blood concentrations.正常人体内垂体激素的刺激分泌:基于血药浓度的新型直接评估方法
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