Comparisons among old and new provocative tests of GH secretion in 178 normal adults

Division of Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy.

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.

This article has been cited by other articles:

				G. Li, J.-P. del Rincon, L. A. Jahn, Y. Wu, B. Gaylinn, M. O. Thorner, and Z. Liu Growth Hormone Exerts Acute Vascular Effects Independent of Systemic or Muscle Insulin-like Growth Factor I J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1379 - 1385. [Abstract] [Full Text] [PDF]

				G. Corneli, C. Di Somma, F. Prodam, J. Bellone, S. Bellone, V. Gasco, R. Baldelli, S. Rovere, H. J. Schneider, L. Gargantini, et al. Cut-off limits of the GH response to GHRH plus arginine test and IGF-I levels for the diagnosis of GH deficiency in late adolescents and young adults Eur. J. Endocrinol., December 1, 2007; 157(6): 701 - 708. [Abstract] [Full Text] [PDF]

				S. Vidarsdottir, M. J. E. Walenkamp, A. M. Pereira, M. Karperien, J. van Doorn, H. A. van Duyvenvoorde, S. White, M. H. Breuning, F. Roelfsema, M. F. Kruithof, et al. Clinical and Biochemical Characteristics of a Male Patient with a Novel Homozygous STAT5b Mutation J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3482 - 3485. [Abstract] [Full Text] [PDF]

				G. Corneli, C. Di Somma, R. Baldelli, S. Rovere, V. Gasco, C. G. Croce, S. Grottoli, M. Maccario, A. Colao, G. Lombardi, et al. The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index Eur. J. Endocrinol., August 1, 2005; 153(2): 257 - 264. [Abstract] [Full Text] [PDF]

				M. J. E. Walenkamp, M. Karperien, A. M. Pereira, Y. Hilhorst-Hofstee, J. van Doorn, J. W. Chen, S. Mohan, A. Denley, B. Forbes, H. A. van Duyvenvoorde, et al. Homozygous and Heterozygous Expression of a Novel Insulin-Like Growth Factor-I Mutation J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2855 - 2864. [Abstract] [Full Text] [PDF]

				M. Maghnie, G. Aimaretti, S. Bellone, G. Bona, J. Bellone, R. Baldelli, C. de Sanctis, L. Gargantini, R. Gastaldi, L. Ghizzoni, et al. Diagnosis of GH deficiency in the transition period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement Eur. J. Endocrinol., April 1, 2005; 152(4): 589 - 596. [Abstract] [Full Text] [PDF]

				X.-D. Qu, I. T. Gaw Gonzalo, M. Y. Al Sayed, P. Cohan, P. D. Christenson, R. S. Swerdloff, D. F. Kelly, and C. Wang Influence of Body Mass Index and Gender on Growth Hormone (GH) Responses to GH-Releasing Hormone Plus Arginine and Insulin Tolerance Tests J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1563 - 1569. [Abstract] [Full Text] [PDF]

				M. Lange, U. Feldt-Rasmussen, O. L. Svendsen, K. W. Kastrup, A. Juul, and J. Muller High Risk of Adrenal Insufficiency in Adults Previously Treated for Idiopathic Childhood Onset Growth Hormone Deficiency J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5784 - 5789. [Abstract] [Full Text] [PDF]

				C. Y. Bowers Unnatural Growth Hormone-Releasing Peptide Begets Natural Ghrelin J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1464 - 1469. [Full Text]

				G. Aimaretti, C. Baffoni, S. Bellone, L. Di Vito, G. Corneli, E. Arvat, L. Benso, F. Camanni, and E. Ghigo Retesting Young Adults with Childhood-Onset Growth Hormone (GH) Deficiency with GH-Releasing-Hormone-Plus-Arginine Test J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3693 - 3699. [Abstract] [Full Text]