Hexarelin-induced growth hormone response in short stature. Comparison with growth hormone-releasing hormone plus pyridostigmine and arginine plus estrogen

Hexarelin (HEX) is a synthetic hexapeptide with strong GH-stimulating activ ity. We evaluated GH response (expressed as maximum value after stimulus [C -max] and as area under the curve [AUC]) to HEX at the doses of 1 mu g/kg i v (HEX 1) and 2 mu g/kg iv (HEX 2), in comparison with the responses to GHR H (1 mu g/kg iv) + pyridostigmine (PD, 60 mg po) and to arginine (ARG, 0.5 mg/kg iv) + ethinylestradiol (EE, 1 mg/day po for 3 days before the stimula tion), in 5 subjects with familial short stature (FSS), 11 with constitutio nal growth delay (CGD), 6 with GH neurosecretory dysfunction (NSD), and 5 w ith isolated growth hormone deficiency (GHD). C-max and AUC after HEX 1 wer e 26.8+/-10.5 ng/ml and 1448+/-514 ng/min x mi in FSS, 23.6+/-14.4 ng/ml an d 1146+/-750 ng/min x mi in CGD, 36.9+/-21.5 ng/ml and 2048+/-1288 ng/min x mi in NSD, 9.4+/-5.8 ng/ml and 498+/-200 ng/min x mi in GHD (C-max and AUC in FSS and CGD, p<0.05 vs GHD). C-max and AUC after HEX 2 were 37.7+/-16 n g/ml and 1979+/-888 ng/min x mi in FSS, 32.5+/-16.2 ng/ml and 1613+/-237 ng /min x mi in CGD, 39.7+/-20.7 ng/ml and 2366+/-1569 ng/min xml in NSD, 13.4 +/-4.2 ng/ml and 645+/-293 ng/min x mi in GHD (C-max in FSS, CGD and NSD p< 0.01 vs GHD; AUC in NSD, p<05 vs GHD). C-max and AUC after GHRH+/-PD were 4 6.6+/-8.8 ng/ml and 3294+/-1031 ng/min x mi in FSS, 25.9+/-11.2 ng/ml and 1 464+/-735 ng/min x mi in CGD, 38.8+/-21.7 ng/ml and 2428+/-1399 ng/min x mi in NSD, 8.4+/-6.2 ng/ml and 685+/-572 ng/min x mi in GHD (C-max and AUC in FSS, p<0.001 vs CGD and GHD; C-max in CGD and NSD, p<0.001 vs GHD). C-max and AUC after ARG+EE were 21.3+/-4.2 ng/ml and 1432+/-514 ng/min x mi in FS S, 14.8+/-10 ng/ml and 805+/-489 ng/min x mi in CGD, 22.2+/-12.8 ng/ml and 1199+/-309 ng/min x mi in NSD, 4.6+/-2.5 ng/ml and 247+/-191 ng/min x mi in GHD (C-max and AUC in FSS, CGD and NSD, p<0.01 vs GHD). Specificity was 62 % for HEX 1 and 75% for HU( 2, GHRH+PD and ARG+EE. From a diagnostic point of view, HEX1 + HEX2 was the association with the largest percentage of fal se positives (20% in FSS, 27% in CGD and 33% in NSD), HEX 1+GHRH+PD resulte d in 9% in CGD, while the combined use of HEX 1 or HEX 2 with GHRH+PD or AR G+EE and of GHRH+PD with ARG+EE did not show false positive responses. In c onclusion: 1) the most effective dose of HEX was 2 mu g/kg iv; 2) HEX did n ot show more specificity than GHRH+PD and ARG+EE; 3) the association of GHR H+PD with ARG+EE could yield the best results at lower costs, confirming th ese tests as first-line tools in evaluating GH secretion. (C) 1999, Editric e Kurtis.