S. Castells et al., HYPOTHALAMIC VERSUS PITUITARY DYSFUNCTION IN DOWNS-SYNDROME AS CAUSE OF GROWTH-RETARDATION, JIDR. Journal of intellectual disability research, 40, 1996, pp. 509-517
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.