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      IGF1 for the diagnosis of growth hormone deficiency in children and adolescents: a reappraisal

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          Abstract

          A number of studies have evaluated the role of IGF1 measurement in the diagnosis of growth hormone deficiency (GHD). This study aimed to evaluate the accuracy and the best cut-off of IGF1 SDS in the diagnosis of GHD in a large cohort of short children and adolescents. One-hundred and forty-two children and adolescents with GHD ((63 organic/genetic (OGHD), 79 idiopathic (IGHD)) and 658 short non-GHD children (median age 10.4 years) were included in the analysis. The two groups were subdivided according to age (G1 <6, G2 6 <9, G3 9 <12, G4 ≥12) and to pubertal status. Serum IGFI was measured by the same chemiluminescence assay in all samples and expressed as age- and sex-based SDS. Receiver operating characteristic (ROC) analysis was used to evaluate the optimal IGF1 SDS cut-off and the diagnostic accuracy. Median IGF1 SDS was significantly lower in the GHD than in non-GHD patients. The area under the curve (AUC) was 0.69, with the best IGF1 cut-off of −1.5 SDS (sensitivity 67.61%, specificity 62.62%). The AUC was 0.75 for OGHD and 0.63 for IGHD. The accuracy was better in the pubertal (AUC = 0.81) than the prepubertal group (AUC = 0.64). In our cohort, IGF1 measurement has poor accuracy in discriminating GHD from non-GHD. Our findings confirm and reinforce the belief that IGF1 values should not be used alone in the diagnosis of GHD but should be interpreted in combination with other clinical and biochemical parameters.

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          Most cited references47

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          Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine.

          The clinical performance of a laboratory test can be described in terms of diagnostic accuracy, or the ability to correctly classify subjects into clinically relevant subgroups. Diagnostic accuracy refers to the quality of the information provided by the classification device and should be distinguished from the usefulness, or actual practical value, of the information. Receiver-operating characteristic (ROC) plots provide a pure index of accuracy by demonstrating the limits of a test's ability to discriminate between alternative states of health over the complete spectrum of operating conditions. Furthermore, ROC plots occupy a central or unifying position in the process of assessing and using diagnostic tools. Once the plot is generated, a user can readily go on to many other activities such as performing quantitative ROC analysis and comparisons of tests, using likelihood ratio to revise the probability of disease in individual subjects, selecting decision thresholds, using logistic-regression analysis, using discriminant-function analysis, or incorporating the tool into a clinical strategy by using decision analysis.
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            Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty.

            New charts for height, weight, height velocity, and weight velocity are presented for clinical (as opposed to population survey) use. They are based on longitudinal-type growth curves, using the same data as in the British 1965 growth standards. In the velocity standards centiles are given for children who are early- and late-maturing as well as for those who mature at the average age (thus extending the use of the previous charts). Limits of normality for the age of occurrence of the adolescent growth spurt are given and also for the successive stages of penis, testes, and pubic hair development in boys, and for stages of breast and pubic hair development in girls.
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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.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                November 2020
                22 October 2020
                : 9
                : 11
                : 1095-1102
                Affiliations
                [1 ]SSD Endocrinologia Pediatrica e Centro Screening Neonatale, Ospedale Pediatrico Microcitemico, ‘A. Cao’ , AO Brotzu, Cagliari, Italy
                [2 ]SSD Endocrinologia Pediatrica , Clinica Pediatrica, IRCCS Materno-infantile Burlo Garofolo, Trieste, Italy
                [3 ]Dipartimento di Pediatria , Università Federico II, Napoli, Italy
                [4 ]Dipartimento di Pediatria , IRCCS Istituto Giannina Gaslini, Università di Genova, Genova, Italy
                [5 ]Dipartimento di Neuroscienze , Riabilitazione, Oftalmologia, Genetica e Scienze Materno-infantili, Università di Genova, Genova, Italy
                [6 ]Dipartimento di Pediatria , Ospedale Generale Regionale, Bolzano, Italy
                [7 ]UOC di Endocrinologia , Dipartimento Universitario Ospedaliero, Ospedale Pediatrico Bambino Gesù IRCCS, Roma, Italy
                Author notes
                Correspondence should be addressed to S Loche: sandro.loche@ 123456aob.it
                Article
                EC-20-0347
                10.1530/EC-20-0347
                7774770
                33112822
                e2e51234-d30c-4e26-913e-49128ea0db47
                © 2020 The authors

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

                History
                : 09 October 2020
                : 22 October 2020
                Categories
                Research

                growth hormone deficiency,insulin-like growth factor 1,children,adolescents,short stature

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