GROWTH-PARAMETERS AND PREDICTORS OF GROWTH IN SHORT CHILDREN WITH ANDWITHOUT GROWTH-HORMONE (GH) DEFICIENCY TREATED WITH HUMAN GH - A RANDOMIZED CONTROLLED-STUDY

Seventy-seven prepubertal short children with heights below the third centile for age and gender were divided into three groups according to their peak GH response to clonidine and insulin provocation. Group (I ) included 30 children with peak GH response <7 mu g/l, group 0 includ ed 19 children, with GH peak response between 7 and 10 mu g/l, and gro up (III) included 24 children with GH peak > 10 mu g/l. Each group was divided into two subgroups, a and b. Subgroups (I)b, (II)a and (III)b were treated daily for 1 year with subcutaneous recombinant human gro wth hormone (GH) 15 U/m(2)/week, and group (I)a was treated with GH (3 0 U/m(2)/week). Before initiation of treatment, the chronological age, the height standard deviation score (HtSDS), and the bone age delay d id not differ among the study subgroups. The height growth velocity (G V) and insulin-like growth factor-I concentrations were significantly higher in group (III), with normal GH response to provocation, compare d to those for group (I) with GH deficiency. All the children had norm al thyroid function and normal glucose tolerance. CT examination of th e hypothalamic-pituitary area revealed a picture of empty sella (eithe r partial or complete) in 35 per cent of the children in group 0 and 2 1 per cent of children in group (II). After 1 year of GH therapy, the HtSDS, GV, and IGF-I concentrations increased significantly in the fou r subgroups treated with GH compared to their pretreatment values and to their controls. All the children in group (I) were responders (incr ement in GV of 2 cm(2)/year above the pretreatment GV), of the nine su bjects treated in group (II)a, one child was a non-responder and of th e 12 children in group (III)a three children were non-responders. GV w as non-significantly higher in group (I)a (30 U/m(2)/week) v. group (I )b (15 U/m(2)/week). GV of children in groups (I)b, with abnormal GH r esponse to provocation, was significantly higher than GV of children i n group (III)a. Bone age advanced by less than 1 year in the treated g roups (0.84 +/- 0.14 years) v. the untreated groups (0.73+/-0.3 years) . None of the children had impaired glucose tolerance or abnormal thyr oid function after 1 year of GH therapy. In all the treated children, GV after 1 year of GH treatment was correlated significantly with the pretreatment GV (r = -0.63, P < 0.01), peak GH response to provocation (r = -0.59, P < 0.01), IGF-I concentration (r = -0.54, P < 0.01), and positively with the GH dose (r = 0.589, P < 0.01). In group (III) chi ldren, with normal GH reserve, GV correlated significantly with the pr etreatment GV (r = -0.48, P < 0.01) and negatively with the GH peak re sponse to provocation (r = -0.25, P < 0.05). In conclusion, GH therapy improved GV of children growing along or parallel to the 3rd centile, irrespective of their GH response to provocation, without untoward ef fect on skeletal maturation, thyroid function or glucose tolerance.