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Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormone-releasing peptide in short children

Klinger B, Silbergeld A, Deghenghi R, Frenkel J, Laron Z. Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormonereleasing peptide in short children. Eur J Endocrinol 1996;134:716–9. ISSN 0804–4643

A clinical, prospective experiment was carried out to determine whether long-term intranasal administration of the growth hormone-releasing peptide hexarelin (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂) affects pituitary growth hormone secretion. Hexarelin (60 µg/kg t.i.d.) was administered to seven prepubertal constitutionally short children (mean age ±SD = 7.6 ± 2.4 years). Serum human growth hormone (hGH) response to an intranasal (20 µg/kg) and intravenous (1 µg/kg) bolus of hexarelin before, during and after 6–10 months of treatment was measured. The mean (±SD) peak rise of hGH to the intranasal bolus before treatment was 70.6 ± mU/I. After 7 days of hexarelin treatment, mean peak values dropped to 34.1 ±15.7 mU/l (p < 0.002) and thereafter 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 velocity 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 intranasal hexarelin treatment, probably due to desensitization, does not affect the observed increase in growth velocity.

Z Laron, Pediatric Endocrinology, 11 El Al Street, Ramat Efal, 52960, Israel