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Continuous subcutaneous GHRH(1-29)NH2 promotes growth over 1 year in short, slowly growing children
C E Brain1, P C Hindmarsh, C G Brook
1Endocrine Unit, Middlesex Hospital, London, UK.
Insights
Continuous GHRH(1-29)NH2 infusions effectively increased growth velocity in children with partial growth hormone (GH) insufficiency. Pulsatile GH secretion was sustained, suggesting GHRH is a viable treatment option for short children.
Area of Science:
- Pediatric Endocrinology
- Growth Hormone Therapy
- Hormone Research
Background:
- Partial growth hormone (GH) insufficiency affects pre-pubertal children.
- Growth hormone-releasing hormone (GHRH) stimulates GH secretion.
- Understanding GHRH's role in GH regulation is crucial for treatment.
Purpose of the Study:
- To evaluate the efficacy and safety of continuous subcutaneous GHRH(1-29)NH2 infusion in children with partial GH insufficiency.
- To assess the impact of GHRH on 24-hour GH secretion profiles.
- To investigate the pituitary's responsiveness to GHRH during treatment.
Main Methods:
- Eight pre-pubertal children with partial GH insufficiency received continuous GHRH(1-29)NH2 infusions (60 ng/kg/min) for up to 1 year.
- Growth velocity and 24-hour GH profiles were monitored.
- Pituitary responsiveness to GHRH bolus was assessed.
Main Results:
- Mean growth velocity increased significantly in children treated for 1 year (4.6 to 7.0 cm/year, P=0.04).
- Similar increases were observed in children treated for 3-6 months.
- Sustained augmentation of pulsatile GH secretion occurred without desensitization.
- Pituitary responsiveness to GHRH remained constant.
Conclusions:
- Continuous GHRH(1-29)NH2 infusion is an effective therapy for some short, slowly growing children with partial GH insufficiency.
- Sustained GH secretion suggests GHRH administration can be a practical treatment.
- Further research is needed to optimize dosage regimens and develop sustained-release formulations.
Abstract:
We have treated eight pre-pubertal children with partial GH insufficiency with continuous subcutaneous infusions of GHRH(1-29)NH2 at a dose of 60 ng/kg/min for periods of up to 1 year. In five children treated for 1 year, mean growth velocity increased from 4.6 cm/year (range 4.4-5.2) to 7.0 cm/year (5.7-8.7) (P = 0.04). Three children treated for 3-6 months showed similar height velocity increases. A return to pretreatment growth rates was seen after cessation of treatment in all children. Twenty-four-hour GH profiles performed at intervals of 3 months showed sustained augmentation of pulsatile GH secretion without evidence of desensitization. The presence of pulsatile GH secretion during continuous GHRH administration provides strong evidence in man for the role of somatostatin in determining GH pulse frequency. The ability of the pituitary to respond to a supramaximal bolus of GHRH remained constant during the treatment. Continuous administration of GHRH(1-29)NH2 will become a practicable treatment when formulated into a sustained release or depot preparation. We have shown this to be an effective therapy for some short, slowly growing children. Further studies are required to establish the optimal dosage regimen.