A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. III. The neuroendocrine growth hormone axis during late prepuberty

Cross-sectional studies demonstrating that physiological GH secretion varies widely among normally and slowly growing children as well as adults have created uncertainty over the definition of normal GH secretion. Furthermore, recent data indicate that the pattern of GH released under identical physiological conditions may be unique for each individual, and suggest that normality may be an individually defined condition. To investigate and develop further this concept and to avoid the confounding effects of fluctuating gonadal steroid hormone levels, we chose as a model normally growing prepubertal boys and performed a longitudinal assessment of spontaneous GH release characteristics (36 24-h GH secretion studies in 9 boys over 9-19 months). Assessment of serum GH pulse characteristics was accomplished using the Cluster pulse detection algorithm. Characteristics of underlying pituitary GH secretory events were estimated by multiple parameter deconvolution analysis. Approximate entropy was used to quantify the serial regularity or orderliness of GH release over 24 h. Among the group data, mean 24-h GH concentrations spanned a range of more than 4-fold (1.6-7.0 μg/L). The intersubject coefficient of variation (CV) was 41%. In contrast, values from individuals exhibited much less variability, not only for mean 24-h GH level (CV-25 ± 4%; P<0.02), but also for all assessed component GH pulse properties (P < 0.01 vs. intersubject values). Similarly, the estimated daily GH production rate, the calculated GH half-lives, and all parameters of GH secretory events varied much less for intraindividual compared to interindividual values. The sizes of the serum GH pulses gave rise to the greatest differences in overall serum GH level among individuals, as demonstrated by the large within-subject CV (50%). The most constant pulse characteristic among subjects was that of 24-h GH pulse frequency (intersubject CV = 30%). Approximate entropy estimates disclosed high within- subject consistency (mean CV = 15%). Several aspects of GH secretion and serum concentrations varied inversely with the subject's mean age-adjusted body mass index, including the 24-h GH production rate (r = -0 67; P < 0.05), the GH secretory burst amplitude (r = -0.73; P = 0.026), the mean serum GH pulse amplitude (r = 0.79; P = 0.011), and the sum of the GH pulse amplitudes (r = -0.66; P = 0.05). By contrast, no consistent pattern of increase or decrease in serum GH concentrations with advancing age was detectable during the prepubertal period. These data suggest that during late prepuberty, 1) individual boys regulate daily GH secretion within relatively confined limits characteristic for that individual, much narrower than the range present in the larger population; 2) differences in mean 24-h GH levels among normally growing prepubertal boys arise primarily from differences in GH pulse size; 3) differences in body composition, as indicated by the body mass index, may influence the GH secretion range characteristic of each individual; and 4) there is no consistent change in mean 24-h GH concentrations or the orderliness (approximate entropy) of the GH release process over time during late prepuberty as the onset of puberty approaches.