DESENSITIZATION FROM LONG-TERM INTRANASAL TREATMENT WITH HEXARELIN DOES NOT INTERFERE WITH THE BIOLOGICAL EFFECTS OF THIS GROWTH HORMONE-RELEASING PEPTIDE IN SHORT CHILDREN

A clinical, prospective experiment was carried out to determine whethe r long-term intranasal administration of the growth hormone-releasing peptide hexarelin (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) affects p ituitary growth hormone secretion, Hexarelin (60 mu g/kg t.i.d.) was a dministered to seven prepubertal constitutionally short children (mean age +/- SD = 7.6 +/- 2.4 years). Serum human growth hormone (hGH) res ponse to an intranasal (20 mu g/kg) and intravenous (1 mu g/kg) bobs o f hexarelin before, during and after 6-10 months of treatment was meas ured, The mean (+/- so) peak rise of hGH to the intranasal bolus befor e treatment was 70.6 +/- 28.2 mU/l. After 7 days of hexarelin treatmen t, mean peak values dropped to 34.1 +/- 15.7 mU/l (p < 0.002) and ther eafter remained constant for 6 months of treatment at 37.5 +/- 10.3 mU /l (p < 0.03), The pretreatment peak to the iv hexarelin bolus was 84. 8 +/- 52.5 mU/l, and at the end of the treatment period it was 19.8 +/ - 10.9 mU/l (p < 0.05). Three months after stopping treatment the mean (+/- SD hGH response rose to 42.1 +/- 4.7 mU/l (p < 0.005). Growth ve locity increased from 5.3 +/- 0.9 cm/year (before treatment) to 7.4 +/ - 1.6 cm/year at 6-10 months of treatment (p < 0.005), In conclusion, the partial suppression of pituitary hGH responsiveness to long-term i ntranasal hexarelin treatment, probably due to desensitization, does n ot affect the observed increase in growth velocity.