title: Subcutaneous growth hormone-releasing hormone augments pulsatile nocturnal GH release in GH-insufficient children, but may also raise basal GH secretion.
abstract: Growth hormone-releasing hormone (GHRH) when given s.c. to GH-insufficient children either as pulses, or once or twice daily, promotes linear growth. These treatment regimens, however, are not ideal as they require frequent drug administration and a significant proportion of patients do not show improved growth. We have now investigated the GH response to a nocturnal s.c. infusion of GHRH (1-29)NH2, at two dosages, 5 and 10 micrograms/kg/h, in a group of five GH-insufficient children. The s.c. infusion of GHRH between 2100 h and 0600 h augmented nocturnal pulsatile GH release in all five children. There was a dose-dependent response for the GH area under the curve (AUC), and mean total GH concentration. The AUC for GH was significantly greater after the 10 than 5 micrograms/kg/h GHRH which in turn was greater than that after placebo; mean (SD) AUC: 14816 (3978), 8125 (1931), 3032 (1582) mU min/l respectively (P less than 0.01 and P less than 0.05). There was no significant change in the number of GH pulses during the 9-h infusions when the subjects were infused with GHRH 10 or 5 micrograms/kg/h compared to placebo, and they occurred at similar times although the number of pulses tended to be greater after GHRH; the mean (SD) numbers of GH pulses were 5.0 (0.7), 3.8 (0.8), 3.2 (0.8), respectively. There was however a significant rise in the mean baseline GH concentration in all patients during the infusion of GHRH 10 micrograms/kg/h compared to placebo, but not with 5 micrograms/kg/h. Thus, GHRH(1-29)NH2 given s.c. augmented nocturnal pulsatile GH release in GH-insufficient children but it also increased baseline GH secretion. These results suggest that a sustained release preparation of GHRH could be a potential treatment for GH-insufficient children, and that a dose of 5 micrograms/kg/h would promote pulsatile GH release, but that at higher dosage it may also raise basal GH secretion.
authors.affiliation: Department of Endocrinology, St Bartholomew's Hospital, London, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Ross
authors.forename: J M
authors.initials: JM
authors.lastname: Kirk
authors.forename: S
authors.initials: S
authors.lastname: Tsagarakis
authors.forename: P J
authors.initials: PJ
authors.lastname: Trainer
authors.forename: E
authors.initials: E
authors.lastname: Ciccarelli
authors.forename: R
authors.initials: R
authors.lastname: Touzel
authors.forename: A
authors.initials: A
authors.lastname: Grossman
authors.forename: M O
authors.initials: MO
authors.lastname: Savage
authors.forename: G M
authors.initials: GM
authors.lastname: Besser
mesh_terms: D002648:Child; D002940:Circadian Rhythm; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D013006:Growth Hormone / Q000172:deficiency* / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D016037:Single-Blind Method
chemical_list: D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone