Chihara Kazuo, Shimatsu Akira, Hizuka Naomi, Tanaka Toshiaki, Seino Yoshiki, Katofor Yuzuru
Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Eur J Endocrinol. 2007 Jul;157(1):19-27. doi: 10.1530/EJE-07-0066.
The international, first-line diagnostic test for adult GH deficiency is the insulin tolerance test (ITT), which is contraindicated in some patients due to severe adverse events. Alternatives such as GH-releasing hormone combined with arginine or GH-releasing peptides (GHRP) have been proposed. We validated the use of GHRP-2 for diagnosing adult GH deficiency (GHD).
Seventy-seven healthy subjects and 58 patients with peak GH<3 microg/l by ITT were enrolled. After overnight fasting, a 100 microg dose of GHRP-2 was administered intravenously; blood samples were taken during the subsequent 2 h and GH measured by immunoradiometric assay.
Serum GH peak occurred within 60 min after GHRP-2 administration in all subjects. GH responses to GHRP-2 were not affected by gender, but were slightly lower in elderly subjects and those with adiposity, although these did not influence diagnosis of GHD. Repeated tests showed favourable reproducibility. Peak GH concentrations after GHRP-2 were significantly (P<0.001) lower in patients (1.36+/-2.60 microg/l) than the healthy group (84.6+/-60.9 microg/l) with no difference between hypothalamic and pituitary diseases. Serum GH concentration at the point where sensitivity of response crossed with specificity ranged from 15 to 20 microg/l. A cut-off value of 15 microg/l for diagnosing GHD with GHRP-2 corresponded to the diagnostic value of 3 microg/l in the ITT.
The GHRP-2 provocative test showed favourable reproducibility and was mildly influenced by age and adiposity. Severe GH deficiency could be diagnosed with high reliability using a 15 microg/l (9 microg/l when GH calibrated with recombinant World Health Organization 98/574 standard) cut-off for peak GH concentration.
胰岛素耐量试验(ITT)是国际上诊断成人生长激素缺乏症的一线诊断试验,但由于严重不良事件,该试验在某些患者中是禁忌的。已提出使用生长激素释放激素联合精氨酸或生长激素释放肽(GHRP)等替代方法。我们验证了GHRP-2在诊断成人生长激素缺乏症(GHD)中的应用。
招募了77名健康受试者和58名ITT检测生长激素峰值<3μg/L的患者。过夜禁食后,静脉注射100μg剂量的GHRP-2;在随后的2小时内采集血样,并通过免疫放射分析测定生长激素。
所有受试者在注射GHRP-2后60分钟内血清生长激素峰值出现。生长激素对GHRP-2的反应不受性别影响,但在老年受试者和肥胖受试者中略低,尽管这些因素不影响GHD的诊断。重复试验显示出良好的可重复性。GHRP-2给药后患者的生长激素峰值浓度(1.36±2.60μg/L)显著低于健康组(84.6±60.9μg/L)(P<0.001),下丘脑和垂体疾病患者之间无差异。反应敏感性与特异性交叉点处的血清生长激素浓度范围为15至20μg/L。用GHRP-2诊断GHD的临界值为15μg/L,相当于ITT中3μg/L的诊断价值。
GHRP-2激发试验显示出良好的可重复性,且受年龄和肥胖的影响较小。使用15μg/L(当生长激素用重组世界卫生组织98/574标准校准后为9μg/L)的生长激素峰值浓度临界值,可以高度可靠地诊断严重生长激素缺乏症。