Intranasal administration of growth hormone‐releasing hormone(1–29)‐NH₂ in children with growth hormone deficiency: effects on growth hormone secretion and growth

Abstract

Intranasal administration of growth hormone-releasing hormone( 1 -29)-NH2 in children with growth hormone deficiency: effects on growth hormone secretion and growth. Acta Paediatr Suppl 1993;388:23-26. Stockholm. ISSN 0803-5326The growth-promoting potential of growth hormone-releasing hormone( 1 -29)-NH, (GHRH( 1-29)-NH,) in a new formulation for intranasal use was examined in a 6-month pilot study of eight short prepubertal children. The maximal plasma concentration of growth hormone (GH) was below 12 pgll in two stimulation tests (arginine, insulin), but above 12 (24-90) pgll after intravenous GHRH, 1 pglkg. GHRH, 50 pg/kg, was insufflated intranasally three times per day over 6 months. On day 1, GHRH insufflations were followed by distinct GHRH and GH plasma peaks, ranging from 1.2 to 5.4 pgll and from 10 to 85 mIU/I, respectively. Peak amplitudes were variably reduced after 6 weeks in most patients, and further reduced at 6 months. GHRH antibodies (initially negative) were positive in three patients after 6 weeks. The mean knemometric growth rate 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 velocity did not increase. Local tolerance was good in one patient; most others reported sneezing immediately after insufflation, rhinorrhoea and mild mucosal burning. Treatment was discontinued in two patients after 6 and 12 weeks. It is concluded that intranasal GHRH, though non-invasive, is not suitable in its present form for use in children, because of decreasing absorption and effectiveness with concomitant development of antibodies and local reactions. 0 Growth hormone deficiency, growth hormone-releasing hormone, intranasal administration, antibodies, growth R Hummelink,