Endogenous growth hormone secretion and clearance rates in normal boys, as determined by deconvolution analysis: Relationship to age, pubertal status, and body mass

Mean plasma GH concentrations increase in normal boys during mid- to late-puberty. To investigate the nature of the pituitary secretory events and/or altered metabolic clearance responsible for these serum GH concentration changes, we performed multiple-parameter deconvolution analysis of 46 24-h serum GH concentration-time series obtained from normal boys at various stages of puberty and young adulthood. The subjects ranged in chronological age from 7-27 yr. The height and weight of each subject were between the 5th and 95th percentile for age. The calculated daily mass of GH secreted was greatest (P < 0.001) in late pubertal boys (mean ± SE, 1810 ± 250 μg/24 h) and was triple the value in prepubertal boys (610 ± 65 μg/24 h). When the values were normalized and expressed as mass of GH secreted per unit (m2) body surface area or per L distribution volume, GH secretion in late pubertal boys was still significantly greater than that in any other group (P < 0.05). These values for late pubertal boys were nearly double the corresponding values for prepubertal boys (1160 ± 160 vs. 600 ± 58 μg GH/m2.24 h and 440 ± 63 vs. 270 ± 25 μg GH/L vol.24 h, respectively). When the effect of clearance mechanics on serum GH concentrations was removed mathematically, the primary change in predicted GH secretory burst parameters during pubertal development was an increase in GH mass released per burst resulting from an increase in the maximal rate of GH secretion attained within the bursts. These changes in the amplitude of GH release events were specific, in that they were largely independent of any accompanying alterations in duration or frequency of the GH secretory bursts or in serum GH half-life. Correlation analysis revealed that the 24-h GH secretion rate varied inversely with the subjects' body mass index SD score (r = -0.65; P < 0.01), suggesting that differences in body mass, even within the normal range, contribute to the wide variability in daily GH secretion rates among normally growing children. The plasma insulin-like growth factor-I concentrations of all subjects correlated positively with the calculated 24-h GH secretion rate (r = 0.51; P < 0.001). In summary, the primary neuroendocrine alteration responsible for the augmented serum GH concentrations characterizing mid- to late-puberty in boys is an increased mass of GH released per pituitary secretory episode resulting from an increased maximal rate of GH secretion within each burst. This Process achieves a daily GH secretion rate during later puberty that is 2- to 3-fold the secretion rate during prepuberty. In addition, body composition, within the normal range, appears to be a physiological modulator of spontaneous GH secretion. These findings suggest that to emulate physiological changes and maximize growth during puberty in GH-deficient children, significant increases in daily GH replacement doses may be required in some individuals.