Hypothalamic versus pituitary dysfunction in Down's syndrome as cause of growth retardation

Abstract

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.

Growth charts of Turkish children with Down syndrome

“…In addition, these patients also have reduced pubertal growth spurt, contributing to the low final height [Cronk et al, 1988;Anner en et al, 1990]. It was demonstrated that children with DS do not have growth hormone (GH) deficiency [Anner en et al, 1986], but hypothalamic dysfunction was reported by Castells et al [1996]. A study performed by Anner en et al [1999] revealed that GH was given to children with DS increased growth velocity.…”

Late effects of early growth hormone treatment in Down syndrome

“…Growth hormone (GH) is known to have a major influence on statural growth by stimulating production of insulin‐like growth factor I (IGF‐I) from the age of 6–9 months, coinciding with the beginning of the pronounced growth retardation in DS. There is no evidence of a general GH deficiency in children with DS (4), but both suboptimal endogenous GH production (5) and selective deficiency of IGF‐I have been observed (6).…”

Normal growth hormone secretion in overweight young adults with Down syndrome

“…Detailed data on secretion of growth hormone (GH) in DS are largely lacking, although suboptimal GH production [2] and selective deficiency of insulin-like growth factor I (IGF-I) [3,4] have been reported in children with DS. Further, abnormalities (e.g.…”