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Augmentation of growth hormone secretion in children with constitutional growth delay by short term clonidine
1Department of Pediatrics, University of Cagliari, Italy.
Insights
Clonidine significantly boosts 24-hour integrated growth hormone secretion (IC-GH) in children with constitutional growth delay (CGD). This treatment also increases insulin-like growth factor I and accelerates growth velocity.
Area of Science:
- Pediatric Endocrinology
- Pharmacology
- Growth Hormone Research
Background:
- Constitutional growth delay (CGD) is characterized by delayed puberty and skeletal maturation.
- Children with CGD often exhibit decreased endogenous growth hormone (GH) secretion.
- Understanding interventions to enhance GH secretion is crucial for managing growth disorders.
Purpose of the Study:
- To evaluate the effect of chronic clonidine administration on 24-hour integrated GH secretion (IC-GH) in children with CGD.
- To assess the impact of clonidine on GH pulse amplitude, GH pulse frequency, insulin-like growth factor I (IGF-I) levels, and growth velocity.
Main Methods:
- Eight children (6 boys, 2 girls; age 6.0-13.0 yr) with CGD received oral clonidine (0.1 mg/m2/day) at bedtime for 6 months.
- 24-hour GH secretion studies were conducted before and after 2 months of treatment.
- Measurements included IC-GH, GH pulse amplitude and frequency, IGF-I levels, and growth velocity.
Main Results:
- Clonidine significantly increased mean IC-GH from 2.6 to 4.6 µg/L (P<0.02).
- The increase in IC-GH was primarily due to enhanced GH pulse amplitude, particularly during awake hours.
- Mean IGF-I levels and growth velocity significantly increased after 2 and 6 months of clonidine treatment.
Conclusions:
- Clonidine effectively increases 24-hour integrated GH secretion in children with CGD.
- The findings support the hypothesis that many children with CGD have diminished endogenous GH secretion.
- Clonidine is a viable therapeutic option for accelerating growth in children diagnosed with constitutional growth delay.
Abstract:
We evaluated the effect of chronic clonidine administration on 24-h integrated GH secretion (IC-GH) in eight children (six boys and two girls; age, 6.0-13.0 yr) with constitutional growth delay (CGD). Clonidine was given orally in a daily dose of 0.1 mg/m2 at bedtime for 6 months; 24-h secretion studies were performed before and after 2 months of treatment. Clonidine caused a significant augmentation (P less than 0.02) of mean IC-GH from 2.6 +/- 0.4 (+/- SE) to 4.6 +/- 0.6 micrograms/L. The increase in IC-GH was mainly the result of increased GH pulse amplitude, which rose from 12.3 +/- 1.3 to 18.2 +/- 2.1 micrograms/L (P less than 0.01). The mean GH pulse amplitude was significantly higher (P less than 0.02) during sleep (15.9 +/- 2.4 micrograms/L) than during the awake hours (8.4 +/- 1.5 micrograms/L) before treatment. During clonidine treatment the mean GH pulse amplitude during the awake hours (15.0 +/- 3.8 micrograms/L) was similar to that during sleep (20.3 +/- 3.1 micrograms/L). GH pulse frequency was not altered by treatment during either the awake or sleep hours. The mean insulin-like growth factor I levels after 2 (1400 +/- 300 U/L) and 6 (1760 +/- 430 U/L) months of treatment were significantly higher (P less than 0.02 and P less than 0.05, respectively) than the pretreatment value (920 +/- 240 U/L). After 2 months of clonidine treatment, growth velocity increased from 3.1 +/- 0.5 to 10.2 +/- 1.0 cm/yr (P less than 0.001), and after 6 months of treatment is was still significantly higher (7.0 +/- 0.7 cm/yr; P less than 0.02) than that before treatment. These results confirm the ability of clonidine to accelerate growth in children with CGD and indicate that clonidine is capable of increasing IC-GH levels. They also reinforce the view that many children with CGD have decreased endogenous GH secretion.