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

Unlabelled: Hexarelin (HEX) is a synthetic hexapeptide with strong GH-stimulating activity. We evaluated GH response (expressed as maximum value after stimulus [Cmax] and as area under the curve [AUC]) to HEX at the doses of 1 microg/kg i.v. (HEX 1) and 2 microg/kg i.v. (HEX 2), in comparison with the responses to GHRH (1 microg/kg i.v.) + pyridostigmine (PD, 60 mg po) and to arginine (ARG, 0.5 mg/kg i.v.) + ethinylestradiol (EE, 1 mg/day po for 3 days before the stimulation), in 5 subjects with familial short stature (FSS), 11 with constitutional growth delay (CGD), 6 with GH neurosecretory dysfunction (NSD), and 5 with isolated growth hormone deficiency (GHD). Cmax and AUC after HEX 1 were 26.8+/-10.5 ng/ml and 1448+/-514 ng/min x ml in FSS, 23.6+/-14.4 ng/ml and 1146+/-750 ng/min x ml in CGD, 36.9+/-21.5 ng/ml and 2048+/-1288 ng/min x ml in NSD, 9.4+/-5.8 ng/ml and 498+/-200 ng/min x ml in GHD (Cmax and AUC in FSS and CGD, p<0.05 vs GHD). Cmax and AUC after HEX 2 were 37.7+/-16 ng/ml and 1979+/-888 ng/min x ml in FSS, 32.5+/-16.2 ng/ml and 1613+/-237 ng/min x ml 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 ml in GHD (Cmax in FSS, CGD and NSD p<0.01 vs GHD; AUC in NSD, p<05 vs GHD). Cmax and AUC after GHRH+/-PD were 46.6+/-8.8 ng/ml and 3294+/-1031 ng/min x ml in FSS, 25.9+/-11.2 ng/ml and 1464+/-735 ng/min x ml in CGD, 38.8+/-21.7 ng/ml and 2428+/-1399 ng/min x ml in NSD, 8.4+/-6.2 ng/ml and 685+/-572 ng/min x ml in GHD (Cmax and AUC in FSS, p<0.001 vs CGD and GHD; Cmax in CGD and NSD, p<0.001 vs GHD). Cmax and AUC after ARG+EE were 21.3+/-4.2 ng/ml and 1432+/-514 ng/min x ml in FSS, 14.8+/-10 ng/ml and 805+/-489 ng/min x ml in CGD, 22.2+/-12.8 ng/ml and 1199+/-309 ng/min x ml in NSD, 4.6+/-2.5 ng/ml and 247+/-191 ng/min x ml in GHD (Cmax and AUC in FSS, CGD and NSD, p<0.01 vs GHD). Specificity was 62% for HEX 1 and 75% for HEX 2, GHRH+PD and ARG+EE. From a diagnostic point of view, HEX 1 + HEX 2 was the association with the largest percentage of false positives (20% in FSS, 27% in CGD and 33% in NSD), HEX 1 +GHRH+PD resulted in 9% in CGD, while the combined use of HEX 1 or HEX 2 with GHRH+PD or ARG+EE and of GHRH+PD with ARG+EE did not show false positive responses.

In Conclusion: I) the most effective dose of HEX was 2 microg/kg i.v.; 2) HEX did not show more specificity than GHRH+PD and ARG+EE; 3) the association of GHRH+PD with ARG+EE could yield the best results at lower costs, confirming these tests as first-line tools in evaluating GH secretion.