506 Short Children Secrete Insufficient Quantities of Growth Hormone

Zadlk, Zvi; Chalew, Stuart A.; Raltl, Salvatore; Kowarski, A. Avinoam

doi:10.1203/00006450-198504000-00536

Cited by 54 publications

(71 citation statements)

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“…In short subjects where the etiology of the condition is probably heterogeneous, differences in IGF-I levels may well reflect differences in G H secretion not detected by pharmacological tests (20)(21)(22). However, Zadik et al (22), studying 24-h integrated GH concentrations, found more than half of the values within the normal range. A possible hypothesis would therefore be that individual variations exist in the expression of the IGF-I gene which accompany normal levels of G H (6).…”

Section: Discussionmentioning

confidence: 97%

Insulin-Like Growth Factor-I Gene Analysis in Subjects with Constitutionally Variant Stature

et al. 1990

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ABSTRACT. The IGF-I gene from leukocyte DNA of a control population of normal stature was studied using Southern blotting. Restriction fragment lengths for 21 enzymes were determined and three restriction fragment length polymorphisms (RFLP) were found (EcoRV, HindIII, and PvuII). In addition, the IGF-I gene of 64 constitutionally short subjects, five Pygmies, and 10 constitutionally tall subjects was analyzed. No IGF-I gene alterations were detectable by Southern blot in any of these conditions. Linkage analysis using genetic markers (RFLP) yielded results that were uninformative for five constitutionally short families investigated, owing to the limited number of RFLP and their low incidence (17% for the 5.2-kb HindIII, 5-kb PvuII RFLP alleles, and 13% for the 13-kb EcoRV RFLP allele). The EcoRV RFLP was found to map near Exon 1. The incidence of the 13-kb polymorphic allele with EcoRV proved to be lower (4%) in the group with constitutionally short stature than in controls. These results could suggest that modifications in the region of the IGF-I gene may be involved in constitutionally short subjects. (Pediatr Res 27:488-491, 1990) Abbreviations constitutionally variant stature were selected on the basis of criteria defined previously (3, 4). Sixty-four short subjects were studied (55 of whom were unrelated). Fifty-eight were children and adolescents, and six were fully grown. Ht was below -2 SD for the French population (7), the average being -2.7 SD. Birth size was 49 cm a 1.2 (mean a SD). The mean body mass index (wt/ht2) was 15.8 k 1.6, which is within the normal range. Five families were also investigated, comprising 24 subjects of whom 13 were constitutionally short. All short subjects had GH levels exceeding 14 ng/mL after ornithine infusion and the mean of the GH peaks (22.7 k 7.3 ng/mL, mean + SD) was no different from that of normals (8). Ten constitutionally tall subjects (nine children and adolescents and one adult) were studied (ht above +2 SD, the mean being +3.4 SD). In all cases, wt was within the normal range (mean f I SD for ht). Thyroid hormone levels were normal in all subjects (free T4: 14.2 + 2.9 pg/mL, TSH:

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Section: Discussionmentioning

confidence: 97%

Insulin-Like Growth Factor-I Gene Analysis in Subjects with Constitutionally Variant Stature

et al. 1990

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“…To date the data point out that the causes are most likely heterogenous, including delay in physical maturity [5][6][7][8][9], suboptimal nutrition [4,10,11], genetic factors and GH-IGF axis abnormalities [4,5,9,[12][13][14]. Therefore a careful investigation of the components related to the GH-IGF-I axis, nutrition and maturity should be carried out in patients with growth failure who are categorized as "idiopathic" or "normal variant" short stature.…”

Section: Discussionmentioning

confidence: 99%

“…The suggested causes of poor growth in children with ISS are most likely heterogenous, i.e. delay in physical maturity [5][6][7][8][9], suboptimal nutrition [4,10,11], genetic factors and growth hormone (GH) -insulin-like growth factor (IGF) axis abnormalities [4,5,9,[12][13][14].…”

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confidence: 99%

Serum Ghrelin, IGF-I and IGFBP-3 Levels In Children with Normal Variant Short Stature

et al. 2006

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Abstract. This study is planned to investigate the role of ghrelin in normal variant short stature. Serum ghrelin, IGF-I and IGFBP-3 levels were measured in 17 children with constitutional delay of growth, 19 children with familial short stature and 11 age matched healthy children. Mean bone age of the constitutional delay of growth group was lower compared to other groups. Constitutional delay of growth group had lower mean weight compared to the controls. Serum IGF-I values were lower in the constitutional delay of growth group compared to the familial short stature and control groups. IGFBP-3 levels of the groups were similar. Ghrelin levels were higher in the short stature groups compared to the controls. In the multiple regression analyses, weight (β = -.54, p<0.0001) and height SDS (β = -.33, p = 0.01) were the independent determinants of ghrelin. The results of this study, the first one in which ghrelin levels are investigated in normal variant short stature, suggest that ghrelin does not play a role as a cause, but as a consequence in these patients because it is negatively correlated with weight and height standard deviation score. These negative correlations can be attributed to the compensatory response of ghrelin, which deserves further attention in future studies.

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“…Causes for CDGP are far from clear. Children with this condition are included, in most studies, in idiopathic short stature, and, whereas normality in the GH secretory dynamics has been reported (22), there are studies that report an impaired GH secretion (23,24), decreased GH binding proteins (25,26) and mutations of the GH receptor in some children with idiopathic short stature (27). Therefore, an abnormality in the GH/IGF-I axis cannot be excluded as a possible factor for the poor mineral density found in CDGP.…”

Section: Journal Of Endocrinology (1998) 139mentioning

confidence: 99%

Bone mineral status in prepubertal children with constitutional delay of growth and puberty

Moreira-Andres¹,

Cañizo²,

Cruz

et al. 1998

European Journal of Endocrinology

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Objective: We wished to clarify whether the osteopenia reported in adult men with a history of constitutional delay of growth and puberty (CDGP) could be due to the delayed puberty or an independent predisposition to osteoporosis in this condition. Design: Short prepubertal children with CDGP and children with familial short stature (FSS) were matched for height and other auxological variables. The FSS children served as a control group. Methods: We measured spinal (L1-L4) bone mineral content (BMC) and bone mineral density (BMD) by dual energy X-ray absorptiometry (Hologic QDR 1000/w) in 56 children aged 5-11 years. All children had height below the 10th percentile for chronological age (CA), and bone age (BA) less than 10 years, 29 of them with clinical diagnosis of possible CDGP and 27 of them with FSS. The BMD standard deviation scores (SDS) relative to the values for normal height children were obtained. Results: The mean (Ϯ S.D.) spinal BMD was significantly lower in the children with CDGP than in the FSS group (0.534 Ϯ 0.059 vs 0.623 Ϯ 0.060 g/cm 2 , P < 0.001). Both groups had negative mean lumbar BMD SDS, but in the CDGP group it was significantly lower than in the FSS group as well when the SDS was based on the CA (¹1.41 Ϯ 0.61 vs ¹0.38 Ϯ 0.51, P < 0.001) and when it was related to BA (¹0.78 Ϯ 0.64 vs ¹0.17 Ϯ 0.52, P < 0.01). BMC was significantly lower in the CDGP than in the FSS group, when multiple regression analysis was performed by using scanned bone area, body weight and height, sex and BA as independent variables (P ¼ 0.0005). Conclusion:The finding of decreased mineralization in prepubertal children with CDGP before the age of puberty suggests that they may have an inherent predisposition to osteopenia.

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506 Short Children Secrete Insufficient Quantities of Growth Hormone

Cited by 54 publications

References 0 publications

Insulin-Like Growth Factor-I Gene Analysis in Subjects with Constitutionally Variant Stature

Insulin-Like Growth Factor-I Gene Analysis in Subjects with Constitutionally Variant Stature

Serum Ghrelin, IGF-I and IGFBP-3 Levels In Children with Normal Variant Short Stature

Bone mineral status in prepubertal children with constitutional delay of growth and puberty

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