Long-term effects of recombinant human growth hormone on children with Down syndrome and growth retardation

Most children with Down syndrome (DS) are markedly retarded in somatic and head growth. Forty children with DS (18 females and 22 males) had L-dopa and clonidine provocative tests of growth hormone (GH), and 3 had 12- or 24-hour integrated GH (iGH) to be compared with those of 7 normal children. The results revealed three different groups based on serum GH peak responses to stimulatory tests: (a) 14 children with low-low peak of serum GH to both L-dopa and clonidine; (b) 24 children with low-normal peak response of serum GH, i.e., a low measurement on one test, L-dopa or clonidine, and a normal one on the other, and (c) 2 children with both tests normal; one had low 12-hour iGH response (0.6 ng per ml), and the other had marked growth retardation. The disparity of responses may reflect a state of diminished GH secretion secondary to hypothalamic dysfunction. We analyze the effects of recombinant human GH (rhGH) in 40 children with DS treated from several months to 6 years and in 12 nontreated children with DS, by using hierarchical linear modelling. The starting height standard deviation score (HSDS) of the comparison group did not differ from the pretreatment scores of the treated group. The pre- and posttreatment HSDS of the treated group were examined as function of age at testing and treatment. Changes in HSDS overtime were related to age at entry into the study, and treatment produced a change of 0.640 SDS units. PAH was calculated by the Roche-Wainer-Thissen method. Predicted adult height (PAH) was calculated during therapy with rhGH in 19 males and 16 females. In males, the mean +/- SD PAH was 170.7 +/- 10.8, and in females, the mean +/- SD PAH was 167.1 +/- 5.2. Serum insulin-like growth factor I during treatment revealed a marked elevation from pretreatment values. There was no increase in blood concentrations of glucose or in hemoglobin A(1c)%. We conclude that treatment with rhGH increases HSDS in prepubertal growth-retarded children with DS, and that PAH normalizes in 91% of the children receiving treatment.