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.

Abstract

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.