Longitudinal changes in growth hormone secretory process irregularity assessed transpubertally in healthy boys

Clarifying the time evolution, and underlying neuroendocrine regulation, of hormone secretion during puberty is of pivotal importance both physiologic ally and clinically. We sought to determine whether clinical growth and ele vated growth hormone (GH) release in pubertal boys are associated with shif ts in the irregularity of GH secretory patterns. We studied GH release in 2 3 healthy boys longitudinally at similar to 4-mo intervals over a 6-yr peri od throughout puberty, by repetitive blood sampling at 20-min intervals for 24 h on each study date. To quantify serial irregularity in the GH profile s, we utilized approximate entropy (ApEn), a scale- and model-independent q uantification of the extent of sequential "randomness." Complementary stati stical analyses establish that on a per-subject basis, serum GH concentrati on-time series show greatest secretory disorderliness (maximal ApEn) in pre puberty and mid-to-late puberty, followed by a steep decline in ApEn to max imal orderliness in postpubertal adolescence (P < 0.0001, ANOVA). Pooling a ll subject comparisons, we observed a persistent positive correlation betwe en ApEn and growth velocity (GrVel), Pearson r = 0.467 (P << 10(-10)). More over, in general, ApEn( GH) preceded GrVel evolution, with a time frame lea d of 4-8 mo providing the most pronounced correlations between ApEn and GrV el. In the setting of low postpubertal growth, per-subject ApEn values fell to approximately one-half of maximal ApEn values and, on average, were in the 13th percentile from minimal (P << 10(-10)) for fully mature boys. Thus , in a longitudinal transpubertal analysis, greater irregularity in GH secr etion corresponds to greater linear growth in boys, which culminates in hig hly regular GH secretory dynamics after sexual maturity. In addition to cli nical utility, there may be added experimental merit in knowing that GH dyn amics typically predict accelerated linear growth in 4-8 mo.