INTRANASAL ADMINISTRATION OF GROWTH HORMONE-RELEASING HORMONE(1-29)-NH2 IN CHILDREN WITH GROWTH-HORMONE DEFICIENCY - EFFECTS ON GROWTH-HORMONE SECRETION AND GROWTH

The growth-promoting potential of growth hormone-releasing hormone(1-2 9)-NH2 (GHRH(1-29)-NH2) in a new formulation for intranasal use was ex amined in a 6-month pilot study of eight short prepubertal children. T he maximal plasma concentration of growth hormone (GH) was below 12 mu g/l in two stimulation tests (arginine. insulin), but above 12 (24-90) mug/l after intravenous GHRH, 1 mug/kg. GHRH, 50 mug/kg, was insuffla ted intranasally three times per day over 6 months. On day 1, GHRH ins ufflations were followed by distinct GHRH and GH plasma peaks, ranging from 1.2 to 5.4 mug/l and from 10 to 85 mIU/l, respectively. Peak amp litudes were variably reduced after 6 weeks in most patients, and furt her reduced at 6 months. GHRH antibodies (initially negative) were pos itive in three patients after 6 weeks. The mean knemometric growth rat e rose from 0.24 to 0.48 mm/week after 6 weeks of treatment (p = 0.03) and then rapidly declined; the mean 6-month stadiometric height veloc ity did not increase. Local tolerance was good in one patient; most ot hers reported sneezing immediately after insufflation, rhinorrhoea and mild mucosal burning. Treatment was discontinued in two patients afte r 6 and 12 weeks. It is concluded that intranasal GHRH, though non-inv asive, is not suitable in its present form for use in children, becaus e of decreasing absorption and effectiveness with concomitant developm ent of antibodies and local reactions.