Hypothalamic versus pituitary dysfunction in Down's 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 deficiency 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 hormone (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 clonidine 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 +/- 5.6 ng ml-1 in controls. Children with DS had a significantly lower 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 microgram kg-1 i.v. bolus and bloods for GH were drawn at-15, 0, 15, 30, 60, 90 and 120 min in 14 subjects with DS and 24 normal controls, both groups prepubertal. The mean delta serum 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-Whitney U-test. These results indicate that levodopa and clonidine (drugs stimulating hypothalamic GHRH release and secondary pituitary GH release in normal individuals) do not stimulate GH release in DS. Furthermore, normal GH response to GHRH in DS indicates normal pituitary function (normal somatotroph response to GHRH) and supports hypothalamic dysfunction in DS.
Castells
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S
Department of Pediatrics-Children's Medical Center, SUNY-Health Science Center at Brooklyn 11203, USA.
Beaulieu
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I
Torrado
C
C
Wisniewski
K E
KE
Zarny
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S
Gelato
M C
MC
D000886:Anthropometry; D002675:Child, Preschool; D003000:Clonidine; D004314:Down Syndrome / Q000175:diagnosis / Q000503:physiopathology*; D004393:Dwarfism, Pituitary / Q000175:diagnosis / Q000503:physiopathology*; D005260:Female; D013007:Growth Hormone-Releasing Hormone; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency*; D006801:Humans; D007027:Hypothalamic Diseases / Q000175:diagnosis / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007223:Infant; D007980:Levodopa; D008297:Male; D012016:Reference Values
D019382:Human Growth Hormone; D007980:Levodopa; D013007:Growth Hormone-Releasing Hormone; D003000:Clonidine