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Somatotropic function in short stature: evaluation by integrated auxological and hormonal indices in 214 children. The Italian Collaborative Group of Neuroendocrinology.

GH secretion was evaluated in 214 children and adolescents (age, 5-16 yr; 160 males and 54 females) with short stature (height, < or = 5th percentile) by assessing mean spontaneous overnight GH concentration (normal values, > or = 3 and 3.9 micrograms/L for prepubertal and pubertal subjects, respectively) and responsiveness to stimulation with GH-releasing hormone combined with pyridostigmine (normal peak values, > or = 20 micrograms/L). Plasma insulin-like growth factor-I (IGF-I) was also measured. According to their GH secretory status, children were grouped as follows: group I, 154 subjects with normal spontaneous and stimulated GH (43 slow-growing and 111 normally growing); group II, 39 subjects with low spontaneous, but normal stimulated, GH (27 slow-growing and 12 normally growing); group III, 18 slow-growing subjects with low spontaneous and stimulated GH; and group IV, 3 subjects with normal spontaneous, but low stimulated, GH. The following conclusions were drawn. 1) Forty-five slow-growing subjects (21% of the total sample) had GH deficiency; 27 (12.6%) belonged to group II (with a preserved GH pituitary reserve, denoting a hypothalamic dysfunction) and 18 (8.4%) to group III (with a reduced GH pituitary reserve). 2) Forty-three slow-growing children in group I had normal GH secretion but low mean IGF-I, which may indicate nutritional problems or a biologically hypoactive GH molecule. 3) The remaining 111 subjects in group I (52%), with normal growth rate, but low mean parental height, were considered as having familial and/or constitutional short stature. GH responses after pyridostigmine plus GH-releasing hormone were normal in all children with a normal growth rate. These findings show that besides clinical evaluation, the assessment of spontaneous GH secretion, GH pituitary reserve, and IGF-I concentration allows proper pathophysiological characterization of short stature. By this approach, the frequency of GH deficiency in our sample was higher than commonly thought.