We report on the auxological and endocrine evolution of 28 patients presenting with Prader-Willi syndrome. Half of them received growth hormone (GH) therapy (group 2). The spontaneous auxological evolution was analyzed in the two groups from 2 to 8 years; the mean SDS for height remained stable (–0.6 ± 0.6) in group 1 and decreased (from –2.0 ± 0.9 to –2.7 ± 0.6) in group 2. Magnetic resonance imaging showed marked pituitary hypoplasia in the two groups. In group 2, the mean GH peak after two provocative tests was 3.8 ± 2.4 µg/l, the mean SDS values for insulin-like growth factor I levels were –2.0 ± 1.5 (range from –0.5 to –5.0). The mean duration of GH treatment was 3.6 ± 2.9 (range 1–9.3) years. 14 children completed 1 year of treatment. The two groups had opposite evolutions in ΔSDS for height (–0.8 ± 0.8 vs. +1.1 ± 0.8), for growth velocity (–1.9 ± 2.2 vs. +2.9 ± 2.7), and for Z score of the body mass index (+0.37 ± 1.3 vs. –0.14 ± 0.76; group 1 vs. group 2). This retrospective study shows that, in children with Prader-Willi syndrome and true GH deficiency, long-term GH therapy is effective in increasing growth velocity and in maintaining body mass index.

The efficacy of GH for increasing adult height (AH) in short adolescents born small for gestational age (SGA) is unclear, due to the lack of long-term controlled trials. A total of 168 short children born SGA (age, 10.5 yr for girls and 12.5 yr for boys) were randomly assigned to receive either 0.067 mg/kg.d GH until attainment of AH or no treatment. In this per-protocol analysis, 91 of 102 patients in the treated group and 33 of 47 patients in the control group were followed to AH. Mean height at inclusion was -3.2 SD score (SDS). Treatment duration was 2.7 +/- 0.6 yr. AH was -2.7 +/- 0.9 and -2.1 +/- 1.0 SDS in the control and treated groups, respectively (P < 0.005). The groups differed by 0.6 SDS units (95% confidence interval, 0.2-0.9). Height gain was 0.5 +/- 0.8 and 1.1 +/- 0.9 SDS in the control and treated groups, respectively (P = 0.002). Multivariate analyses confirmed the independent effects of treatment (0.6 SDS) and treatment duration (0.4 SDS/yr). All potential biases would tend to decrease the estimate of the treatment effect. Treatment tolerance was excellent. We concluded that the potential for spontaneous catch-up in short adolescents born SGA is limited. GH treatment increases AH by at least 0.6 SDS in this population.

GH state and auxological data after completion of GH therapy are reported in 131 patients (79 males, 52 females). They were treated from 1980-1994 for partial (n = 98) or complete (n = 33) GH deficiency (GHD), either idiopathic (n = 121) or organic (n = 10). A single stimulation test (clonidine+betaxolol) was used, and only 50 patients (38%) maintained a blunted response (GH peak below 10 micrograms/L). Although 9 of the 10 patients with organic GHD had an abnormal low GH peak, 67% of patients with idiopathic GHD normalized their GH secretion. This was particularly true of partial GHD patients (71% vs. 36% of complete GH-deficient patients). Based on a retest GH peak below 5 micrograms/L, only 23% of the patients were considered to be GH deficient and therefore candidates for GH treatment during adulthood. We found no significant difference between hormonal state at completion of treatment and initial GH deficiency, pubertal state, or sex, although we did find a significantly lower GH peak value before and after treatment in patients with elevated body mass index. Of the 14 obese children who were treated, 50% had an abnormally low serum insulin-like growth factor-I level, arguing for true GHD, and only two children remained obese at cessation of treatment. Auxological data showed that with a mean duration of treatment of 3.6 +/- 2.0 yr, patients classified as having complete GHD before treatment had significantly greater catch-up growth as expressed in SDS for height than patients with partial GHD (0.6 +/- 1.1 vs. 1.1 +/- 0.7 SDS, P < 0.05), and that boys grew better than girls (1.4 +/- 0.8 vs. 1.6 +/- 0.6 SDS) for height, P < 0.01). That catch-up growth was not correlated with the result of GH peak after cessation of treatment.

Objectives: To describe the growth of children treated with growth hormone and to evaluate the prognostic factors for height at the end of treatment. Design: Register based cohort study. Setting: French national register of all children treated with growth hormone.

Seventy-eight prepubertal, non-GH-deficient children aged 8.1 +/- 0.2 y, with very short stature (mean, -3.2 SD) of intrauterine onset, were treated for 3 y with GH [0.4 (dose D1) or 1.2 (dose D2) IU/kg/wk] and 66 were followed during a 4th y without GH therapy. A 2-y intermediary report had demonstrated a GH dose-dependent acceleration of growth. During the 3rd y on GH, patients D2 (1.2 IU/kg/wk) continued with the same dose, whereas patients D1 (0.4 IU/kg/wk) were randomized to either continue on D1 (group D1) or be increased to D2 (group D1D2). After 3 y on GH, patients' mean height (SD) reached -2.37 (D1), -2.17 (D1D2), and -1.58 (D2) with a total mean height gain of 0.77 (D1), 0.93 (D1D2) (difference NS), and 1.61 SD (D2 significantly higher than D1 and D1D2, p < or = 0.0001). During the off-treatment year, mean growth rate (cm/y) decreased to 3.4 in patients D1, 3.7 in D1D2, and 4.1 in D2 (NS). During the 4 y, bone age advanced of 4.6, 4.6, and 5.3 y in D1, D1D2, and D2, respectively, and puberty started in 34 patients (10 during the off-treatment year). Age at onset of puberty, apparently within normal range, did not relate either to the dose or the duration of treatment. Clinical and biologic tolerance of treatment was good. In conclusion this study demonstrates a GH dose-dependent effect on growth acceleration in persistent postnatal severe growth retardation of intrauterine onset. This effect was sustained for 3 y at 1.2 IU/kg/wk followed by a peculiar growth deceleration at treatment discontinuation. Additional studies are necessary to optimize long-term GH treatment regimen and to document its effects on final height.