Regular fluctuations in growth hormone (GH) release determine normal human growth

Growth hormone (GH) is the principal hormone associated with growth through childhood, but in a normal child the amount of GH secretion does not appear to be critical in the generation of normal growth rates. We have assessed the relationship between growth and urinary GH (uGH) output in a longitudinal study of 29 healthy prepubertal schoolchildren (13 male, 16 female; age 5.7-7.8 years) over 1 year. Height and uGH were measured three times a week. Individual height velocity curves were derived using non- linear regression. Growth was expressed in terms of the total increment over the year (ΔHt, cm), height velocity standard deviation score (HVSDS) and the average size of individual growth spurts. Urinary GH data (ng) were expressed as a weekly average. Mean uGH did not correlate with stature or growth over the year. However, the coefficient of variation of uGH was correlated with height standard deviation score (HtSDS, r = 0.38, P <0.05), while the relative constancy of short-term change in uGH (coefficient of incremental change, Δ(INC)) was inversely correlated with ΔHt (r = - 0.44) and HVSDS (r= - 0.42, both P <0.05) but not with HtSDS. Δ(INC) was also inversely correlated with the average size of individual growth spurts derived from the height velocity curves (r = - 0.45, P <0.05). Using time series analysis to identify rhythms in uGH excretion, a positive correlation was found between the magnitude of rhythms of a period of 2 to 4 weeks and HtSDS (r= 0.40, P <0.05). These data demonstrate that variability in GH is a more important determinant of normal childhood growth rate than the amount of GH alone. Stature is correlated to the overall variability in GH release, while increment in height and the magnitude of individual growth spurts are influenced by the constancy of the GH profile. This would imply that once the GH dose has been replaced in GH deficiency, optimal growth could only be achieved by varying the pattern of GH administration.