Hexarelin, a synthetic six‑amino‑acid peptide, can trigger a big growth‑hormone (GH) surge when given at 2 µg per kg of body weight by IV. However, its ability to correctly identify GH‑deficient people isn’t better than cheaper tests that combine a GH‑releasing hormone (GHRH) with pyridostigmine or arginine with low‑dose estrogen. For DIYers, the higher dose works best, but the IV route and lack of extra specificity make it less attractive than the cheaper oral/IV combos.

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. 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.