GROWTH-HORMONE RELEASING ACTIVITY BY INTRANASAL ADMINISTRATION OF A SYNTHETIC HEXAPEPTIDE (HEXARELIN)

OBJECTIVE Hexarelin is a new synthetic growth hormone releasing peptid e. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intrave nous (i.v.) administration of the peptide. PATIENTS Ten children with familial short stature (FSS) aged 5.5-15.5 years and two known GH defi cient patients aged 24 and 28 years without GH treatment. METHODS All 12 subjects were submitted to i.v. (1 mu g/kg) and i.n. (20 mu g/kg) h exarelin tests with a one-week interval between tests. Blood samples f or GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minu tes. The hormone determinations were made by standard radioimmunoassay s (RIA). RESULTS Both the i.n. and i.v. administration of hexarelin In duced a large GH response, the mean (+/- SD) being 72.2 +/- 35.5 mU/I for the i.n. test and 79.6 +/- 53.0 mU/I for the i.v. test. The peak G H in the i.v. test occurred at 15-30 minutes and in the i.n. test betw een 30 and 60 minutes. The GH deficient patients showed no GH response in either test. Plasma TSH decreased in the FSS children from a mean (+/- SD) of 1.0 +/- 0.26 to 0.64 +/- 0.2 mU/I (P < 0.005) during the i .n. test and from 1.0 +/- 0.3 to 0.7 +/- 0.3 mU/I (P < 0.05) during th e i.v. test. In the isolated GH deficient patient, plasma TSH decrease d from 1.06 +/- 0.38 mU/I to 0.86 +/- 0.17 during the i.v. test and fr om 1.60 +/- 0.01 to 1.11 +/- 0.06 mU/I during the i.n. test. There wer e no significant changes in plasma fT4 or T3 in any of the tests. CONC LUSIONS The synthetic hexapeptide hexarelin is a potent pituitary GH s timulator when administered intranasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there wa s a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and p ractical relevance to the investigation and management of short childr en.