HYPOTHALAMIC VERSUS PITUITARY DYSFUNCTION IN DOWNS-SYNDROME AS CAUSE OF GROWTH-RETARDATION

We have found that some children with Down's syndrome (DS) have growth retardation secondary to growth hormone (GH) deficiency. To test the hypothesis that hypothalamic dysfunction is the primary cause for GH d eficiency and growth retardation, hypothalamic-pituitary responses of serum GH concentrations to levodopa and clonidine as well as pituitary responses in serum GH concentrations to growth-hormone-releasing horm one (GHRH) were analysed in 14 prepubertal children with DS. Levodopa and clonidine were given, and blood was drawn for determining serum GH levels. Seven prepubertal control children had both levodopa and clon idine tests done. The Delta serum GH during levodopa was 5.7+/-6.3 ng ml(-1) in DS and 13.1+/-9.8 ng ml(-1) in controls. The Delta serum GH during clonidine administration was 3.0+/-3.2 ng ml(-1) in DS and 17.3 1+/-5.6 ng ml(-1) in controls. Children with DS had a significantly lo wer response to levodopa and clonidine, compared with controls by the Mann-Whitney U-test (P<0.03 and P<0.009, respectively). Growth-hormone -releasing hormone was given at 1 mu g kg(-1) i.v. bolus and bloods fo r GH were drawn at -15, 0, 15, 30, 60, 90 and 120 min in 14 subjects w ith DS and 24 normal controls, both groups prepubertal. The mean a ser um GH concentration in DS was 53.6+/-38.3 ng ml(-1) and it was 35.6+/- 25.1 ng ml(-1) in controls with P<0.23 non-significant by the Mann-Whi tney U-test. These results indicate that levodopa and clonidine (drugs stimulating hypothalamic GHRH release and secondary pituitary GH rele ase in normal individuals) do not stimulate GH release in DS. Furtherm ore, normal GH response to GHRH in DS indicates normal pituitary funct ion (normal somatotroph response to GHRH) and supports hypothalamic dy sfunction in DS.