Peak and trough growth hormone (GH) concentrations influence growth and serum insulin like growth factor-1 (IGF-1) concentrations in short children

OBJECTIVE Growth hormone (GH) is secreted in a pulsatile fashion promoting growth and a number of diverse metabolic actions. The precise components of the pulsatile signal involved in growth regulation are unclear. DESIGN A retrospective analysis of 24 h serum GH concentration profiles to evaluate the relative contribution of peak and trough serum GH concentratio ns to growth regulation, GH response to insulin induced hypoglycaemia (ITT) and serum insulin like growth factor-1 (IGF-1) concentration. PATIENTS Fifty short prepubertal children (age 5.2-11.9 years). MEASUREMENT Analysis of the hormone profile by a concentration distribution method that determines the concentration at or below which the serum GH co ncentrations in the 24 hour profile spend a percentage of the total time. T he method generates an estimate of the observed concentrations (OC) below w hich 95 % and 5 % of the values in the time series lie: OC 95 (peaks) and O C5 (troughs). RESULTS Twenty six of the children were growing at a normal rate for short children with a height velocity standard deviation score (HVSDS) between +0 .4 and -0.8 whereas twenty four were growing more slowly (HVSDS between -0. 9 to -3.9). The former group had a mean peak GH response to ITT of 27.3 (11 .1) mU/l whereas the latter had a mean value of 8.7 (6.5) mU/l, There was n o relationship between (peak and trough GH concentration) and the age of th e individual or body mass index. Peak GH levels were positively related to HVSDS and serum IGF-1 values (r = 0.44; P = 0.002 and r = 0.53; P = 0.002, respectively). GH trough levels were inversely related to these measurement s (r = -0.29; P = 0.05; and r = -0.46; P = 0.002, respectively). Further an alysis showed that individuals with the slowest growth rates and lowest IGF -1 concentrations had the lowest peak and highest trough GH concentrations (ANOVA F = 6.0; P = 0.002). Similarly, the peak GH response to ITT was lowe st in those individuals with high troughs and low peaks (ANOVA F = 9.99; P < 0.001). CONCLUSIONS These results suggest that the peak values of a GH concentratio n profile influence growth rate and the IGF-1 axis whereas elevated trough values have the greatest influence on growth rate and IGF-1 values when GH peaks are low.