Corneli Ginevra, Di Somma Carolina, Prodam Flavia, Bellone Jaele, Bellone Simonetta, Gasco Valentina, Baldelli Roberto, Rovere Silvia, Schneider Harald Jörn, Gargantini Luigi, Gastaldi Roberto, Ghizzoni Lucia, Valle Domenico, Salerno Mariacarolina, Colao Annamaria, Bona Gianni, Ghigo Ezio, Maghnie Mohamad, Aimaretti Gianluca
Endocrinology, Department of Clinical and Experimental Medicine, Amedeo Avogadro University of Novara, Via Solaroli, 17, 28100 Novara, Italy.
Eur J Endocrinol. 2007 Dec;157(6):701-8. doi: 10.1530/EJE-07-0384.
To define the appropriate diagnostic cut-off limits for the GH response to GHRH+arginine (ARG) test and IGF-I levels, using receiver operating characteristics (ROC) curve analysis, in late adolescents and young adults.
We studied 152 patients with childhood-onset organic hypothalamic-pituitary disease (85 males, age (mean+/-s.e.m.): 19.2+/-0.2 years) and 201 normal adolescents as controls (96 males, age: 20.7+/-0.2 years). Patients were divided into three subgroups on the basis of the number of the other pituitary hormone deficits, excluding GH deficiency (GHD): subgroup A consisted of 35 panhypopituitary patients (17 males, age: 21.2+/-0.4 years), subgroup B consisted of 18 patients with only one or with no more than two pituitary hormone deficits (7 males, age: 20.2+/-0.9 years); and subgroup C consisted of 99 patients without any known hormonal pituitary deficits (60 males, age: 18.2+/-0.2 years). Both patients and controls were lean (body mass index, BMI<25 kg/m(2)). Patients in subgroup A were assumed to be GHD, whereas in patients belonging to subgroups B and C the presence of GHD had to be verified.
For the GHRH+ARG test, the best pair of highest sensitivity (Se; 100%) and specificity (Sp; 97%) was found choosing a peak GH of 19.0 microg/l. For IGF-I levels, the best pair of highest Se (96.6%) and Sp (74.6%) was found using a cut-off point of 160 microg/l (SDS: -1.3). Assuming 19.0 microg/l to be the cut-off point established for GHRH+ARG test, 72.2% of patients in subgroup B and 39.4% in subgroup C were defined as GHD. In patients belonging to group B and C and with a peak GH response <19 microg/l to the test, IGF-I levels were lower than 160 microg/l (or less than 1.3 SDS) in 68.7 and 41.6% of patients respectively predicting severe GHD in 85.7% of panhypopituitary patients (subgroup A).
In late adolescent and early adulthood patients, a GH cut-off limit using the GHRH+ARG test lower than 19.0 microg/l is able to discriminate patients with a suspicion of GHD and does not vary from infancy to early adulthood.
通过受试者操作特征(ROC)曲线分析,确定青少年晚期和青年成人中生长激素(GH)对生长激素释放激素(GHRH)+精氨酸(ARG)试验反应及胰岛素样生长因子-I(IGF-I)水平的合适诊断截断值。
我们研究了152例儿童期起病的器质性下丘脑-垂体疾病患者(85例男性,年龄(均值±标准误):19.2±0.2岁)和201例正常青少年作为对照(96例男性,年龄:20.7±0.2岁)。根据除生长激素缺乏(GHD)外其他垂体激素缺乏的数量,将患者分为三个亚组:A亚组由35例全垂体功能减退患者组成(17例男性,年龄:21.2±0.4岁),B亚组由18例仅有一种或不超过两种垂体激素缺乏的患者组成(7例男性,年龄:20.2±0.9岁);C亚组由99例无任何已知垂体激素缺乏的患者组成(60例男性,年龄:18.2±0.2岁)。患者和对照均体型偏瘦(体重指数,BMI<25kg/m²)。A亚组患者被假定为GHD,而B亚组和C亚组患者中GHD的存在需予以证实。
对于GHRH+ARG试验,选择GH峰值为19.0μg/L时,灵敏度(Se)和特异度(Sp)最佳组合分别为100%和97%。对于IGF-I水平,截断点为160μg/L(标准差评分:-1.3)时,Se和Sp最佳组合分别为96.6%和74.6%。假设将19.0μg/L作为GHRH+ARG试验的截断点,则B亚组72.2%的患者和C亚组39.4%的患者被定义为GHD。在B组和C组中且对该试验的GH峰值反应<19μg/L的患者中,分别有68.7%和41.6%的患者IGF-I水平低于160μg/L(或低于1.3标准差评分),这在85.7%的全垂体功能减退患者(A亚组)中提示严重GHD。
在青少年晚期和青年成人患者中,使用GHRH+ARG试验时,GH截断值低于19.0μg/L能够鉴别疑似GHD的患者,且从婴儿期到青年成人期该截断值无变化。