Augmentation of Growth Hormone Secretion in Children With Constitutional Growth Delay by Short Term Clonidine Administration: A Pulse Amplitude-Modulated Phenomenon*

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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 augmentatin (P < 0.02) of mean IC-GH from 2.6 .+-. 0.4 (.+-. SE) to 4.6 .+-. 06 .mu.g/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 .mu.g/L (P < 0.01). The mean GH pulse amplitude was significantly higher (P < 0.02) during sleep (15.9 .+-. 2.4 .mu.g/L) than during the awake hours (8.4 .+-. 1.5 .mu.g/L) before treatment. During clonidine treatment the mean GH pulse amplitude during the awake hours (15.0 .+-. 3.8 .mu.g/L) was similar to that during sleep (20.3 .+-. 3.1 .mu.g/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 U 430 U/L) months of treatment were significantly higehr (P < 0.02 and P < 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 < 0.001), and after 6 months of treatment is was still significantly higher (7.0 .+-. 0.7 cm/yr; P < 0.02) than that before treatment. These results confirm the ability to 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.