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

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Abstract

Hexarelin (HEX) is a synthetic hexapeptide with strong GH-stimulating activity. 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 μg/kg iv (HEX 1) and 2 μg/kg iv (HEX 2), in comparison with the responses to GHRH (1 μg/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). C(max) 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 (C(max) and AUC in FSS and CGD, p <0.05 vs GHD). C(max) 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 (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 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 (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 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 (C(max) 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 μg/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.

Original languageEnglish
Pages (from-to)360-368
Number of pages9
JournalJournal of Endocrinological Investigation
Volume22
Issue number5
Publication statusPublished - 1999

Keywords

  • Arginine
  • Estrogen priming
  • GHRH
  • Hexarelin
  • Pyridostigmine
  • Short stature

ASJC Scopus subject areas

  • Endocrinology

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