Aimaretti G, Baffoni C, DiVito L, Bellone S, Grottoli S, Maccario M, Arvat E, Camanni F, Ghigo E
Division of Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy.
Eur J Endocrinol. 2000 Apr;142(4):347-52. doi: 10.1530/eje.0.1420347.
Classical provocative stimuli of GH secretion such as insulin-induced hypoglycaemia, arginine, clonidine, glucagon and levodopa have been widely used in clinical practice for approximately 30 years. On the other hand, in the last 10 years new potent stimuli of GH secretion have been proposed, but an extensive comparison with the classical ones has rarely been performed, at least in adults. In order to compare the GH-releasing activity of old and new provocative stimuli of GH secretion, and to define the normative values of the GH response, in 178 normal adults (95 males, 83 females; age range: 20-50 years, all within +/-15% of their ideal body weight), we studied the GH response to: insulin-induced hypoglycaemia (ITT, 0.1IU/kg i.v.), arginine (ARG, 0.5g/kg i.v.), clonidine (CLO, 300 microg/kg p.o.), glucagon (GLU, 1mg i.m.), pyridostigmine (PD, 120mg p.o.), galanin (GAL, 80pmol/kg per min), GH-releasing hormone (GHRH, 1 microg/kg i.v.), GHRH+ARG, GHRH+PD, hexarelin, a GH-releasing protein (HEX, 2 microg/kg i.v.) and GHRH+HEX (0.25 microg/kg i.v.). The mean (+/-s.e.m.) peak GH response to ITT (21.8+/-2.8, range: 3.0-84.0 microg/l) was similar to those to ARG (18.0+/-1.6, range: 2.9-39.5 microg/l) or GLU (20. 5+/-2.2, range: 10.6-36.9 microg/l) which, in turn, were higher (P<0. 001) than those to CLO (8.2+/-1.6, range: 0.3-21.5 microg/l), PD (9. 6+/-1.1, range: 2.2-33.0 microg/l) and GAL (9.3+/-1.1, range: 3.9-18. 3 microg/l). The GH response to GHRH (19.1+/-1.5, range: 2.7-55.0 microg/l) was similar to those after ITT, ARG or GLU but clearly lower than those after GHRH+ARG (65.9+/-5.5, range: 13.8-171.0 microg/l) and GHRH+PD (50.2+/-4.6, range: 17.7-134.5 microg/l) which, in turn, were similar. The GH response to HEX (55.3+/-5.5, range: 13.9-163.5 microg/l) was similar to those after GHRH+ARG and GHRH+PD but lower (P<0.001) than that after GHRH+HEX (86.0+/-4.3, range: 49. 0-125.0 microg/l) which was the most potent stimulus of GH secretion. In this adult population the third centile limits of peak GH response to various stimuli were the following: ITT: 5.3; ARG: 2.9; CLO: 1.5; GLU: 7.6; PD: 2.2; GAL: 4.0; GHRH: 5.0; GHRH+ARG: 17.8; GHRH+PD: 17.9; HEX: 21.6; GHRH+HEX: 57.1. These results confirm that, among classical provocative tests of GH secretion, ITT followed by ARG and GLU are the most potent ones and possess clear limits of normality. GHRH+ARG or PD and HEX are strong stimuli of GH secretion which, however, is maximally stimulated by a combination of GHRH and a low dose of HEX. It is recommended that each test is used with appropriate cut-off limits.
生长激素(GH)分泌的经典激发刺激,如胰岛素诱导的低血糖、精氨酸、可乐定、胰高血糖素和左旋多巴,已在临床实践中广泛应用约30年。另一方面,在过去10年中,已提出了新的强效GH分泌刺激,但至少在成年人中,很少与经典刺激进行广泛比较。为了比较新旧GH分泌激发刺激的GH释放活性,并确定GH反应的正常参考值,我们对178名正常成年人(95名男性,83名女性;年龄范围:20 - 50岁,均在其理想体重的±15%范围内)研究了GH对以下刺激的反应:胰岛素诱导的低血糖(ITT,静脉注射0.1IU/kg)、精氨酸(ARG,静脉注射0.5g/kg)、可乐定(CLO,口服300μg/kg)、胰高血糖素(GLU,肌肉注射1mg)、吡啶斯的明(PD,口服120mg)、甘丙肽(GAL,每分钟静脉注射80pmol/kg)、生长激素释放激素(GHRH,静脉注射1μg/kg)、GHRH + ARG、GHRH + PD、六肽生长激素释放肽(一种GH释放蛋白,HEX,静脉注射2μg/kg)以及GHRH + HEX(静脉注射0.25μg/kg)。ITT的平均(±标准误)峰值GH反应(21.8±2.8,范围:3.0 - 84.0μg/L)与ARG(18.0±1.6,范围:2.9 - 39.5μg/L)或GLU(20.5±2.2,范围:10.6 - 36.9μg/L)相似,而这又高于CLO(8.2±1.6,范围:0.3 - 21.5μg/L)、PD(9.6±1.1,范围:2.2 - 33.0μg/L)和GAL(9.3±1.1,范围:3.9 - 18.3μg/L)(P<0.001)。GHRH的GH反应(19.1±1.5,范围:2.7 - 55.0μg/L)与ITT、ARG或GLU后的反应相似,但明显低于GHRH + ARG(65.9±5.5,范围:13.8 - 171.0μg/L)和GHRH + PD(50.2±4.6,范围:17.7 - 134.5μg/L),而后两者相似。HEX的GH反应(55.3±5.5,范围:13.9 - 163.5μg/L)与GHRH + ARG和GHRH + PD后的反应相似,但低于GHRH + HEX(86.0±4.3,范围:49.0 - 125.0μg/L)(P<0.001),GHRH + HEX是最强的GH分泌刺激。在该成年人群中,各种刺激的峰值GH反应的第三百分位数界限如下:ITT:5.3;ARG:2.9;CLO:1.5;GLU:7.6;PD:2.2;GAL:4.0;GHRH:5.0;GHRH + ARG:17.8;GHRH + PD:17.9;HEX:21.6;GHRH + HEX:57.1。这些结果证实,在经典的GH分泌激发试验中,ITT其次是ARG和GLU是最有效的,并且具有明确的正常界限。GHRH + ARG或PD以及HEX是GH分泌的强刺激,但GHRH与低剂量HEX联合使用时对GH分泌的刺激最大。建议每个试验使用适当的截断界限。