One Year of GH Treatment for Growth Failure in Children With Anorexia Nervosa: A Randomized Placebo-Controlled Trial.

CONTEXT: Children with anorexia nervosa (AN) are at risk of adult height deficit due to prolonged low height velocity (HV). OBJECTIVE: To investigate the effects of human growth hormone (GH) injections on HV in children with AN and severe growth impairment. DESIGN AND PARTICIPANTS: In this prospective, randomized, double-blind, single-center, proof-of-concept trial, children with AN and low HV (≤2 cm/year) for at least 18 months, and a bone age ≤12 years for girls and ≤14 years for boys, were randomized to receive daily subcutaneous injections of human GH (0.050 mg/kg/day) or placebo for 12 months. MAIN OUTCOME MEASURES: Change in HV after 12 months. RESULTS: In total, 8 patients were assigned to the GH group and 6 to the placebo group. Patients had a median (25th-75th percentile) HV of 1.0 (0.5;1.5) cm/year. The effect of GH treatment increased strongly after 6 months, with a height gain after 12 months of 9.65 (8.0;11.6) cm for the GH group vs 3.85 (1.7;7.3) cm for the placebo group, with an absolute median (2.5th-97.5th percentile) difference between the groups of 5.8 (-1.85;9.68) cm after bootstrapping. The percentage of patients with a HV > 5 cm/year during the study period was higher in the GH group than in the placebo group (100% vs 50%, P = 0.05). Adverse events occurred in similar numbers in the 2 groups, were mild or nonfatal, and did not lead to treatment being stopped. CONCLUSION: GH administration to improve HV is a potentially valid option for increasing HV in children with AN and prolonged severe growth failure.

Can growth hormone treatment improve growth in children with severe growth failure due to anorexia nervosa? A preliminary pilot study.

BACKGROUND/AIMS: Growth failure is a difficult but key aspect of care in children with anorexia nervosa (AN). The effects of hGH therapy have not been studied. The aim was to investigate the effect of hGH treatment on height velocity (HV) in children with AN. METHODS: We carried out a retrospective observational study. Ten girls diagnosed with AN at 10.0 ± 1.9 years, with prolonged severe growth failure (HV < 2.5 cm/year for at least 18 months) at the age of 13.3 ± 1.1 years and delayed puberty after nutritional rehabilitation, were treated with hGH (0.040 mg/kg/day) from a bone age of 10.9 ± 1.7 years until they reached adult height. Height and HV were measured before treatment and at 12-month intervals during treatment. RESULTS: Mean body mass index SDS remained unchanged, but HV increased significantly, from a median of 1.0 (0.7-2.1) to 7.1 (6.0-9.5) cm/year after one year (P < 0.002) and 5.6 (4.8-6.2) cm/year after two years of treatment. Height SDS increased from -2.2 ± 1.3 to -1.6 ± 1.3 after one year (P < 0.002) and -1.1 ± 1.5 after two years of GH treatment. Adult height (-0.1 ± 1.0 SDS) was close to target height after 3.6 ± 1.4 years of GH treatment. Serum IGF-I levels increased significantly during treatment (P < 0.01). The treatment was well tolerated. CONCLUSIONS: This proof-of-concept study shows that hGH treatment is associated with significant improvements in linear growth in adolescents with AN and severe growth failure. A randomized placebo-controlled trial is required to determine the ultimate impact of GH treatment in patients with this severe, rare condition.

Short children born small for gestational age and treated with growth hormone for three years have an important catch-down five years after discontinuation of treatment.

The potential benefits of GH treatment, resulting in a significant height gain in children born small for gestational age (SGA), have been well documented for the last 10-15 yr. There is, however, no consensus on how to treat patients to attain a normal adult height. We have previously reported in a controlled study that recombinant human GH (1.4 IU/kg.wk or 0.47 mg/kg.wk) given daily induces an important increase in height velocity (HV) in young SGA children with severe short stature. Consequently, a total gain of 2 SD score (SDS) in height resulted in a mean height of -1.3 +/- 0.8 SDS after 3 yr of treatment. The aim of the present report was to assess the consequences of interruption of GH treatment during a 5-yr follow-up period on HV, height, bone age (BA), puberty, and glucose tolerance in SGA children. There was a dramatic decrease of HV SDS, especially evident during the early part of the observation period, with a loss of 3.9 HV SDS during the first year. After 5 yr off treatment, mean HSDS was -2.2 +/- 1.2, still above the pretreatment level (P < 0.0001). Consequently, the interruption of GH administration resulted in a reduction of 1 SDS in height. However, BA did not advance more than 4 yr, and the ratio Delta BA/Delta chronological age at follow-up was similar to pretreatment values. Sixty percent of the children started puberty during the follow-up, and the chronological age and BA at the onset of puberty were 11.4 +/- 1.0 yr and 10.9 +/- 0.5 yr in girls, and 12.1 +/- 1.4 yr and 11.3 +/- 1.1 yr in boys, respectively. Oral glucose tolerance testing after 1 yr and up to several years after discontinuation of GH therapy showed only minor, variable, and inconclusive changes in glucose tolerance. In conclusion, we have shown that tolerance and safety data during and after GH treatment continue to be reassuring. A reduction of HV SDS and height SDS 5 yr after interruption of GH therapy is a strong argument for a continuous GH treatment or a discontinuous treatment with short fall-off intervals at least until puberty.