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

, : Hexarelin-induced growth hormone response in short stature. Comparison with growth hormone-releasing hormone plus pyridostigmine and arginine plus estrogen. Journal of Endocrinological Investigation 22(5): 360-368

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 mug/kg iv (HEX 1) and 2 mug/kg iv (HEX 2), in comparison with the responses to GHRH (1 mug/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 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: 1) the most effective dose of HEX was 2 mug/kg iv; 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.


PMID: 10401710

DOI: 10.1007/BF03343574

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