GROWTH-HORMONE SECRETION IN CHILDREN WITH NORMAL VARIANTS OF SHORT STATURE

Pulsatile growth hormone (GH) secretion plays a central role in human growth during the prepubertal period of life. In order to investigate whether or not short stature in prepubertal children with normal varia nts of short stature (NVSS) may be explained, at least in part, by the presence of abnormalities in the pulsatile pattern of GH secretion, w e have studied the spontaneous secretion of GH/24 h in 139 prepubertal children with short stature (less than or equal to -2 SD) and normal growth velocity (>-1 SD) and in 37 prepubertal children with normal he ight and growth velocity. Ah of the subjects included in this study ex hibited a body mass index (BMI) lower than 1 SD. The patients with sho rt stature were divided into three groups according to their bone age and the existence of familial antecedents of short stature. These grou ps were: (1) familial short stature without bone age retardation (FSS- 1); (2) constitutional, nonfamilial short stature, with bone age retar dation suggesting further delay of puberty (possible constitutional de lay of growth and puberty), and (3) familial short stature with bone a ge retardation (FSS-2). Spontaneous GH secretion was analyzed by using a computerized mathematical algorithm of pulsatility (Cluster(R)). In addition, in all of the patients with short stature, the GH secretory response to three different pharmacological stimuli was evaluated, in cluding: clonidine, growth hormone-releasing hormone (GHRH) and hypogl ycemia after insulin administration. The mean values of GH/24 h exhibi ted a wide range of distribution (1.4-7.8 ng/ml). No significant diffe rences were found in the mean values of GH/24 h, the number of secreto ry bursts of GH/24 h, the maximum peak height of GH/24 h, the pulsatil e GH area under the curve, the total area under the curve or the GH in tegrated concentration/24 h between any of the groups studied. Approxi mately 35.8% of the children in every group, including the normal cont rols, exhibited mean values of GH/24 h lower than 3 ng/ml. Nonextracte d insulin-like growth factor 1 (IGF-1) serum levels were similar in al l of the experimental groups. Furthermore, the mean level of GH respon se to insulin, clonidine, and GHRH was also similar in the three group s of children with short stature. No significant differences were foun d between the different spontaneous GH secretory parameters nor the GH response to pharmacological stimuli nor the nonextracted IGF-1 serum levels. In addition, we did not find any significant correlations betw een GH secretion and any of the auxological parameters studied, includ ing: chronological age, height (SD score), BMI (SD score), growth velo city (SD score), bone age or the parental mean height. In conclusion, our results suggest that during the prepubertal period of life: (1) th e short stature of patients with NVSS is not due to an abnormality in the pattern of GH secretion; (2) the mean values of GH/24 h in normal children, as well as in children with NVSS, show a wide variability an d overlap with values from children with classical GH deficiency, and (3) the measurements of GH secretion, whatever the methods used, do no t correlate with auxological parameters in nonobese children with NVSS .