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      The growth hormone–insulin-like growth factor-I axis in the diagnosis and treatment of growth disorders

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          Abstract

          The growth hormone (GH)–insulin-like growth factor (IGF)-I axis is a key endocrine mechanism regulating linear growth in children. While paediatricians have a good knowledge of GH secretion and assessment, understanding and use of measurements of the components of the IGF system are less current in clinical practice. The physiological function of this axis is to increase the anabolic cellular processes of protein synthesis and mitosis, and reduction of apoptosis, with each being regulated in the appropriate target tissue. Measurement of serum IGF-I and IGF-binding protein (IGFBP)-3 concentrations can complement assessment of GH status in the investigation of short stature and contribute to prediction of growth response during GH therapy. IGF-I monitoring during GH therapy also informs the clinician about adherence and provides a safety reference to avoid over-dosing during long-term management.

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          Most cited references66

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          Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency

          Background/Aims: On behalf of the Drug and Therapeutics, and Ethics Committees of the Pediatric Endocrine Society, we sought to update the guidelines published in 2003 on the use of growth hormone (GH). Because idiopathic short stature (ISS) remains a controversial indication, and diagnostic challenges often blur the distinction between ISS, GH deficiency (GHD), and primary IGF-I deficiency (PIGFD), we focused on these three diagnoses, thereby adding recombinant IGF-I therapy to the GH guidelines for the first time. Methods: This guideline was developed following the GRADE approach (Grading of Recommendations, Assessment, Development, and Evaluation). Results: This guideline provides recommendations for the clinical management of children and adolescents with growth failure from GHD, ISS, or PIGFD using the best available evidence. Conclusion: The taskforce suggests that the recommendations be applied in clinical practice with consideration of the evolving literature and the risks and benefits to each individual patient. In many instances, careful review highlights areas that need further research.
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            Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop.

            Our objective was to summarize important advances in the management of children with idiopathic short stature (ISS). Participants were 32 invited leaders in the field. Evidence was obtained by extensive literature review and from clinical experience. Participants reviewed discussion summaries, voted, and reached a majority decision on each document section. ISS is defined auxologically by a height below -2 sd score (SDS) without findings of disease as evident by a complete evaluation by a pediatric endocrinologist including stimulated GH levels. Magnetic resonance imaging is not necessary in patients with ISS. ISS may be a risk factor for psychosocial problems, but true psychopathology is rare. In the United States and seven other countries, the regulatory authorities approved GH treatment (at doses up to 53 microg/kg.d) for children shorter than -2.25 SDS, whereas in other countries, lower cutoffs are proposed. Aromatase inhibition increases predicted adult height in males with ISS, but adult-height data are not available. Psychological counseling is worthwhile to consider instead of or as an adjunct to hormone treatment. The predicted height may be inaccurate and is not an absolute criterion for GH treatment decisions. The shorter the child, the more consideration should be given to GH. Successful first-year response to GH treatment includes an increase in height SDS of more than 0.3-0.5. The mean increase in adult height in children with ISS attributable to GH therapy (average duration of 4-7 yr) is 3.5-7.5 cm. Responses are highly variable. IGF-I levels may be helpful in assessing compliance and GH sensitivity; levels that are consistently elevated (>2.5 SDS) should prompt consideration of GH dose reduction. GH therapy for children with ISS has a similar safety profile to other GH indications.
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              Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                June 2018
                03 May 2018
                : 7
                : 6
                : R212-R222
                Affiliations
                [1 ]University Children’s Hospital Giessen, Germany
                [2 ]Al Habib Medical Group Riyadh, Saudi Arabia
                [3 ]King Faisal Specialist Hospital and Research Center Riyadh, Saudi Arabia
                [4 ]Department of Pediatric Endocrinology & Diabetes Hamad Medical Center, Doha, Qatar
                [5 ]Tawam Hospital Al Ain, UAE
                [6 ]Global Medical Affairs Endocrinology Merck KGaA, Darmstadt, Germany
                [7 ]William Harvey Research Institute Barts and the London School of Medicine & Dentistry, London, UK
                Author notes
                Correspondence should be addressed to M O Savage: m.o.savage@ 123456qmul.ac.uk
                Article
                EC180099
                10.1530/EC-18-0099
                5987361
                29724795
                d28d168e-de2d-4349-ab59-3bad9f782c83
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 25 April 2018
                : 03 May 2018
                Categories
                Review

                growth hormone,paediatrics,short stature,insulin-like growth factor-i,insulin-like growth factor,binding protein-3

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