05 December 2008
Normal variants of short stature, Growth, Growth hormone, Growth hormone secretion, Insulin-like growth factor I, Short normal children, Familiar short stature, Constitutional delay of growth and puberty
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 variants of short stature (NVSS) may be explained, at least in part, by the presence of abnormalities in the pulsatile pattern of GH secretion, we have studied the spontaneous secretion of GH/24 h in 139 prepubertal children with short stature (≤ -2 SD) and normal growth velocity ( > -1 SD) and in 37 prepubertal children with normal height and growth velocity. All of the subjects included in this study exhibited a body mass index (BMI) lower than 1 SD. The patients with short stature were divided into three groups according to their bone age and the existence of familial antecedents of short stature. These groups were: (1) familial short stature without bone age retardation (FSS-1); (2) constitutional, nonfamilial short stature, with bone age retardation suggesting further delay of puberty (possible constitutional delay of growth and puberty), and (3) familial short stature with bone age retardation (FSS-2). Spontaneous GH secretion was analyzed by using a computerized mathematical algorithm of pulsatility (Cluster®). In addition, in all of the patients with short stature, the GH secretory response to three different pharmacological stimuli was evaluated, including: clonidine, growth hormone-releasing hormone (GHRH) and hypoglycemia after insulin administration. The mean values of GH/24 h exhibited a wide range of distribution (1.4-7.8 ng/ml). No significant differences were found in the mean values of GH/24 h, the number of secretory bursts of GH/24 h, the maximum peak height of GH/24 h, the pulsatile GH area under the curve, the total area under the curve or the GH integrated concentration/24 h between any of the groups studied. Approximately 35.8% of the children in every group, including the normal controls, exhibited mean values of GH/24 h lower than 3 ng/ml. Nonextracted insulinlike growth factor 1 (IGF-1) serum levels were similar in all of the experimental groups. Furthermore, the mean level of GH response to insulin, clonidine, and GHRH was also similar in the three groups of children with short stature. No significant differences were found 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 between GH secretion and any of the auxological parameters studied, including: chronological age, height (SD score), BMI (SD score), growth velocity (SD score), bone age or the parental mean height. In conclusion, our results suggest that during the prepubertal period of life: (1) the 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 and overlap with values from children with classical GH deficiency, and (3) the measurements of GH secretion, whatever the methods used, do not correlate with auxological parameters in nonobese children with NVSS.