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(1-29)-NH2 (GHRH(1-29)-NH2) 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 micrograms/l in two stimulation tests (arginine, insulin), but above 12 (24-90) micrograms/l after intravenous GHRH, 1 microgram/kg. GHRH, 50 micrograms/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 micrograms/l and from 10 to 85 mIU/l, 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.
Hümmelink
R
R
Department of Paediatrics, University of Kiel, Germany.
Sippell
W G
WG
Benoit
K G
KG
Danielson
K
K
Faijerson
Y
Y
D000281:Administration, Intranasal; D000365:Age Determination by Skeleton; D001827:Body Height / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002648:Child; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D013006:Growth Hormone / Q000097:blood / Q000172:deficiency* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007866:Leg / Q000254:growth & development; D008297:Male; D010865:Pilot Projects; D012220:Rhinitis / Q000139:chemically induced; D017337:Sermorelin / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use
D007334:Insulin-Like Growth Factor I; D017337:Sermorelin; D013006:Growth Hormone