hexarelin and Hypoglycemia

Insulin-induced hypoglycemia (ITT) is currently the "gold-standard" test for the diagnosis of adult growth hormone deficiency (GHD). ITT is often contraindicated, however, particularly in conditions that are also common in patients with suspected GHD. Used alone, GH-releasing hormone (GHRH) has no diagnostic value owing to within-subject variability and the inability to distinguish GHD from normal subjects. When combined with arginine, however, GHRH becomes a potent and reproducible test, which is unaffected by gender and aging, showing excellent specificity. The GHRH+ arginine (ARG) test distinguishes GHD patients from normal subjects and is at least as sensitive as ITT, provided that appropriate cutoff limits are considered. Its reliability for retesting GHD has also been demonstrated. The GHRH+ARG test can also be performed in a shorter procedure, resulting in potential for cost reduction. Synthetic GH secretagogues (GHSs) possess a strong and reproducible GH-releasing effect and synergize with GHRH. The combination of GHRH and a peptidyl GHS, such as hexarelin or GH-releasing peptide-6, has recently been shown as another reliable test for the diagnosis of adult GHD, again provided that the cutoff limit is appropriate to the potency of the test. Thus, GHRH combined with either arginine or GHS is a potential tool for the diagnosis of adult GHD.

Topics: Adult; Arginine; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Hypoglycemia; Insulin; Oligopeptides; Reproducibility of Results; Sensitivity and Specificity

GH deficiency (GHD) in adults must be shown by provocative testing of GH secretion. Insulin-induced hypoglycemia (ITT) is the test of choice, and severe GHD, treated with recombinant human GH replacement, is defined by a GH peak response to ITT of less than 3 microg/L. GHRH plus arginine (ARG) is a more provocative test and is as sensitive as ITT provided that appropriate cut-off limits are assumed. GH secretagogues are a family of peptidyl and nonpeptidyl GH-releasing molecules that strongly stimulate GH secretion and, even at low doses, truly synergize with GHRH. Our aim was to verify the diagnostic reliability of the hexarelin (HEX; 0.25 microg/kg, iv) and GHRH (1 microg/kg, iv) test for the diagnosis of adult GHD. To this goal, in the present study we 1) defined the normal ranges of the GH response to GHRH+HEX in a group of normal young adult volunteers (NS; n = 25; 18 men and 7 women; age, 28.5+/-0.6 yr) and in 11 of them verified its reproducibility in a second session, and 2) compared the GH response to GHRH+HEXwith that to ITT in a group of normal subjects (n = 33; 12 men and 21 women; age, 34.1+/-1.5 yr) and hypopituitaric adults with GHD (n = 19; 10 men and 9 women; age, 39.9+/-2.2 yr; GH peak <5 microg/L after ITT). The GH response to GHRH+ARG was also evaluated in all GHD and in 77 normal subjects (40 men and 37 women; age, 28.1+/-0.6 yr). The mean GH peak after GHRH+HEX in NS was 83.6+/-4.5 microg/L; the third and first percentile limits of the normal GH response were 55.5 and 51.2 microg/L, respectively). The GH response to GHRH+HEX in NS showed good intraindividual reproducibility. In GHD the mean GH peak after GHRH+HEX (2.6+/-0.7 microg/L) was similar to that after GHRH+ARG (3.6+/-1.0 microg/L), and both were higher (P < 0.001) than that after ITT (0.6+/-0.1 microg/L); the GH responses to GHRH+HEX were positively associated with those to ITT and GHRH+ARG. Analyzing individual GH responses, 100% had severe GHD after ITT (GH peak, <3 microg/L). After GHRH+HEX all GHD had GH peaks below the third percentile limit of normality appropriate for this test (i.e. 55.5 microg/L). Thirteen of 19 (68.4%) GHD subjects had GH peaks below 3 microg/L after GHRH+HEX but all 19 (100%) had GH peaks below the first percentile limit of normality (i.e. 51.2 microg/L). The GH responses to GHRH+HEX were highly concordant with those after GHRH+ARG. In conclusion, the present results define normal limits of the GH response to stimulation with low dose HEX+GHRH in n

Topics: Adult; Female; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Hypoglycemia; Insulin; Male; Middle Aged; Oligopeptides