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      Effect of zinc supplementation on growth Hormone Insulin growth factor axis in short Egyptian children with zinc deficiency

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          Abstract

          Background

          The relationship between zinc (Zn) and growth hormone-insulin growth factor (GH-IGF) system and how Zn therapy stimulates growth in children has not been clearly defined in humans. Thus, we aimed to assess GH-IGF axis in short children with Zn deficiency and to investigate the effect of Zn supplementation on these parameters.

          Methods

          Fifty pre-pubertal Egyptian children with short stature and Zn deficiency were compared to 50 age-, sex-, and pubertal stage- matched controls. All subjects were subjected to history, auxological assessment and measurement of serum Zn, IGF-1, insulin growth factor binding protein-3 (IGFBP-3); and basal and stimulated GH before and 3 months after Zn supplementation (50 mg/day).

          Results

          After 3 months of Zn supplementation in Zn-deficient patients, there were significant increases in height standard deviation score (SDS, P = 0.033), serum Zn (P < 0.001), IGF-1 (P < 0.01), IGF-1 standard deviation score (SDS,P < 0.01) and IGFBP-3 (P = 0.042). Zn rose in all patients but reached normal ranges in 64 %, IGF-1 levels rose in 60 % but reached normal ranges in 40 % and IGFBP-3 levels rose in 40 % but reached reference ranges in 22 %. Growth velocity (GV) SDS did not differ between cases and controls (p = 0.15) but was higher in GH-deficient patients than non-deficient ones, both having Zn deficiency (p = 0.03).

          Conclusion

          Serum IGF-1 and IGFBP-3 levels were low in short children with Zn deficiency, and increased after Zn supplementation for 3 months but their levels were still lower than the normal reference ranges in most children; therefore, Zn supplementation may be necessary for longer periods.

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          Most cited references26

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          Standards from birth to maturity for height, weight, height velocity, and weight velocity: British children, 1965. I.

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            Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3).

            Assays for insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) have become essential tools in the diagnostic work-up of disorders of the somatotropic axis in children and adults. The aim of this study was to evaluate the automated IMMULITE IGF-I and IGFBP-3 assays and to establish reference limits--central 95% intervals, median, 0.1 and other centiles as clinically relevant--as a function of age from 797 females and 787 males, from the first week of life through the ninth decade. Pubertal children were classified by sex and by sexual maturation (Tanner stage). IGF-I and IGFBP-3 levels were also assayed in 20 pediatric patients each with growth hormone deficiency (GHD) and Turner syndrome (UTS), before and during 12 months of recombinant growth hormone (rhGH) therapy, as well as in 11 adult patients with GHD and seven with acromegaly before therapy. Both the IGF-I and IGFBP-3 assays were accurate, specific and sufficiently sensitive to measure IGF-I and IGFBP-3 in serum with good linearity and recovery. In the IGF-I assay, potential interference from IGFBPs was eliminated by blocking with excess IGF-II. Circulating IGF-I and IGFBP-3 concentrations, and their ratio IGF-I/IGFBP-3, were age-dependent, showing low levels immediately after birth, a typical pubertal peak for girls and boys, and a pronounced decline after puberty, reaching a plateau in early adulthood. In adults IGF-I and IGFBP-3 levels decreased smoothly but steadily with age. Children with GHD and UTS had low circulating IGF-I and IGFBP-3 levels which increased to normal reference limits under therapy with rhGH. Adult GHD patients showed IGF-I levels below the age-related median; untreated acromegalic patients mostly had IGF-I and IGFBP-3 levels above the age-related 97.5th centile. In conclusion, the automated IMMULITE IGF-I and IGFBP-3 assays are reliable tools in the diagnosis of pathologies of the GH/IGF axis and in the follow-up of their therapies.
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              Zinc: an overview.

              Zn deficiency in humans is widespread throughout the world. It is more prevalent in areas where the population subsists on cereal proteins. Conditioned Zn deficiency is seen in many disease states. Its deficiency during growth periods results in growth failure and lack of gonadal development in males. Other effects of Zn deficiency include skin changes, poor appetite, mental lethargy, delayed wound healing, neurosensory disorders, and cell-mediated immune disorders. Severe Zn deficiency, as seen in acrodermatitis enteropathica (a genetic disorder), is fatal if Zn is not administered to these patients. A clinical diagnosis of marginal Zn deficiency in humans remains problematic. Assays of Zn in granulocytes and lymphocytes provide better diagnostic criteria for marginal Zn deficiency than plasma Zn. Approximately 300 enzymes are known to require Zn for their activities. Zn is required for DNA synthesis, cell division, and protein synthesis. Recently, we learned that Zn-finger proteins are involved in genetic expression of various growth factors and steroid receptors. We suspect that several hundred Zn-containing nucleoproteins are probably involved in gene expression of various proteins. Zn deficiency adversely affects lymphocyte proliferation. This may be related to the enzymatic role of Zn in DNA synthesis and cell division. Thymulin, a thymic hormone involved in T-lymphocyte maturation, is known to be Zn dependent and is adversely affected by Zn deficiency. Thus, an adverse effect of Zn deficiency may also be in lymphocyte differentiation and maturity. Zn deficiency is known to decrease interleukin 2 production by helper T lymphocytes, and abnormalities in T-lymphocyte subpopulations have been observed in Zn-deficient humans.(ABSTRACT TRUNCATED AT 250 WORDS)
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                Author and article information

                Journal
                Ital J Pediatr
                Ital J Pediatr
                Italian Journal of Pediatrics
                BioMed Central
                1824-7288
                2012
                24 May 2012
                : 38
                : 21
                Affiliations
                [1 ]Department of Pediatrics, Ain Shams University, 36 Hisham Labib street, off Makram Ebeid street, Nasr City, Cairo, Egypt
                [2 ]Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
                [3 ]Department of Clinical and Chemical Pathology, National Research Center, Cairo, Egypt
                Article
                1824-7288-38-21
                10.1186/1824-7288-38-21
                3453500
                22625223
                3ed31ced-0e70-4a04-b22d-ffa93e69bd63
                Copyright ©2012 Hamza et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 September 2011
                : 24 May 2012
                Categories
                Research

                Pediatrics
                insulin growth factor-1,growth hormone,egyptian,zinc
                Pediatrics
                insulin growth factor-1, growth hormone, egyptian, zinc

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