Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency
Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency
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DOI：
10.1210/jc.87.5.2067
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发表时间：
2002-05-01
影响因子：
5.8
通讯作者：
Hartman, ML
中科院分区：
文献类型：
--
作者：
Biller, BMK;Samuels, MH;Hartman, ML
虽然使用胰岛素耐量试验（ITT）诊断成人GH缺乏症已得到很好的确立，但其他常用GH刺激试验的诊断峰值GH临界点尚不明确。尽管如此，在美国，大多数接受GH缺乏症评估的患者不接受胰岛素耐受性测试。本研究的目的是评估目前在美国实践中使用的六种不同的成人GH缺乏症检测方法的相对效用，并为每种检测方法制定诊断临界点。研究了39例成人型下丘脑-垂体疾病和多种垂体激素缺乏症患者（26例男性，13例女性），并与年龄、性别、雌激素状态和体重指数匹配的对照组（n = 34; 20例男性，14例女性）进行了比较。第三组患者（n = 21）与成人发病的下丘脑-垂体疾病和不超过一个额外的垂体激素缺乏症也进行了研究。主要终点是在5次单独访视时对5种GH刺激试验（ITT、精氨酸（ARG）、左旋多巴（L-DOPA）、ARG + L-DOPA和ARG + GHRH）的峰值血清GH反应。还在两种情况下测量血清IGF-I浓度。为了分析的目的，假设患有多种垂体激素缺乏症的患者为GH缺乏症。根据以下三个标准，计算每项试验的三个诊断临界点，以提供多种垂体激素缺乏症和对照受试者的最佳分离：1）尽量减少对照受试者和缺乏症患者的错误分类（高灵敏度和高特异性之间的平衡）; 2）为GH缺乏症提供95%的灵敏度; 3）为GH缺乏症提供95%的特异性。ITT和ARG + GHRH试验的诊断准确性最高，尽管患者更喜欢后者（P = 0.001）。ITT使用5.1 μ g/L的血清GH峰值临界点，ARG加GHRH试验使用4.1 μ g/L的血清GH峰值临界点，获得了GH缺乏症的高灵敏度（分别为96%和95%）和特异性（分别为92%和91%）。为了获得95%的特异性，ITT和ARG加GHRH测试的血清GH峰值分界点分别较低，为3.3 μ g/L和1.5 μ g/L。在ARG + L-DOPA、ARG和L-DOPA试验中，患者和对照受试者之间存在大量重叠，但可以为所有三种试验定义试验特异性临界点，以提供95%的GH缺乏敏感性（峰值GH临界点：分别为1.5、1.4和0.64 μ g/L）。然而，95%的特异性可以实现与ARG加L-DOPA和ARG测试只有非常低的峰值GH临界点（0.25和0.21 μ g/L，分别），而不是在所有的L-DOPA测试。虽然血清IGF-I水平提供的诊断区分度低于所有五种GH刺激试验，但低于77.2 μ g/L的值对GH缺乏症的特异性为95%。总之，如果使用检测特异性临界点，则无需进行ITT即可诊断成人GH缺乏症。ARG加GHRH测试是诊断成人GH缺乏症的ITT的绝佳替代方案。
Although the use of the insulin tolerance test (ITT) for the diagnosis of adult GH deficiency is well established, diagnostic peak GH cut-points for other commonly used GH stimulation tests are less clearly established. Despite that fact, the majority of patients in the United States who are evaluated for GH deficiency do not undergo insulin tolerance testing. The aim of this study was to evaluate the relative utility of six different methods of testing for adult GH deficiency currently used in practice in the United States and to develop diagnostic cut-points for each of these tests. Thirty-nine patients (26 male, 13 female) with adult-onset hypothalamic-pituitary disease and multiple pituitary hormone deficiencies were studied in comparison with age-, sex-, estrogen status-, and body mass index-matched control subjects (n = 34; 20 male, 14 female). A third group of patients (n = 21) with adult-onset hypothalamic-pituitary disease and no more than one additional pituitary hormone deficiency was also studied. The primary end-point was peak serum GH response to five GH stimulation tests administered in random order at five separate visits: ITT, arginine (ARG), levodopa (L-DOPA), ARG plus L-DOPA, and ARG plus GHRH. Serum IGF-I concentrations were also measured on two occasions. For purposes of analysis, patients with multiple pituitary hormone deficiencies were assumed to be GH deficient. Three diagnostic cut-points were calculated for each test to provide optimal separation of multiple pituitary hormone deficient and control subjects according to three criteria: 1) to minimize misclassification of control subjects and deficient patients (balance between high sensitivity and high specificity); 2) to provide 95% sensitivity for GH deficiency; and 3) to provide 95% specificity for GH deficiency. The greatest diagnostic accuracy occurred with the ITT and the ARG plus GHRH test, although patients preferred the latter (P = 0.001). Using peak serum GH cut-points of 5.1 mug/liter for the ITT and 4.1 mug/liter for the ARG plus GHRH test, high sensitivity (96 and 95%, respectively) and specificity (92 and 91%, respectively) for GH deficiency were achieved. To obtain 95% specificity, the peak serum GH cut-points were lower at 3.3 mug/liter and 1.5 mug/liter for the ITT and ARG plus GHRH test, respectively. There was substantial overlap between patients and control subjects for the ARG plus L-DOPA, ARG, and L-DOPA tests, but test-specific cut-points could be defined for all three tests to provide 95% sensitivity for GH deficiency (peak GH cut-points: 1.5,1.4 and 0.64 mug/liter, respectively). However, 95% specificity could be achieved with the ARG plus L-DOPA and ARG tests only with very low peak GH cut-points (0.25 and 0.21 mug/liter, respectively) and not at all with the L-DOPA test. Although serum IGF-I levels provided less diagnostic discrimination than all five GH stimulation tests, a value below 77.2 mug/liter was 95% specific for GH deficiency. In conclusion, the diagnosis of adult GH deficiency can be made without performing an ITT, provided that test-specific cut-points are used. The ARG plus GHRH test represents an excellent alternative to the ITT for the diagnosis of GH deficiency in adults.