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      Predictors of transient congenital hypothyroidism in children with eutopic thyroid gland

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          Abstract

          Purpose

          Congenital hypothyroidism (CH) is the most common cause of preventable mental retardation. Recently, the detection of CH cases with eutopic thyroid gland has increased due to neonatal screening programs. In this study, we aimed to identify and evaluate predictive factors that could distinguish between permanent and transient CH in patients with eutopic thyroid gland.

          Methods

          We retrospectively reviewed 100 children diagnosed with CH and with eutopic thyroid gland. All subjects were treated with levothyroxine and underwent re-evaluation after 3 years of age.

          Results

          Of the 100 CH patients, 35 (35.0%) were diagnosed with permanent CH (PCH) and 65 (65.0%) were diagnosed with transient CH (TCH). The initial thyroid stimulating hormone levels were significantly lower in the TCH subjects than in PCH subjects. In addition, the mean doses of levothyroxine (µg/kg/day) at the 1st, 2nd, and 3rd year of treatment were significantly lower in subjects with TCH than in PCH subjects with eutopic thyroid gland. Based on the receiver operating characteristic (ROC) curve, the optimal cutoff dose of levothyroxine at 3 years of 2.76 µg/kg/day could predict TCH, and was associated with 87.3% sensitivity and 67.6% specificity, with an area under the ROC curve of 0.769.

          Conclusion

          The levothyroxine dose requirement during treatment period has a predictive role in differentiating TCH from PCH in CH patients with eutopic thyroid gland.

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          Most cited references13

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          Understanding diagnostic tests 3: Receiver operating characteristic curves.

          The results of many clinical tests are quantitative and are provided on a continuous scale. To help decide the presence or absence of disease, a cut-off point for 'normal' or 'abnormal' is chosen. The sensitivity and specificity of a test vary according to the level that is chosen as the cut-off point. The receiver operating characteristic (ROC) curve, a graphical technique for describing and comparing the accuracy of diagnostic tests, is obtained by plotting the sensitivity of a test on the y axis against 1-specificity on the x axis. Two methods commonly used to establish the optimal cut-off point include the point on the ROC curve closest to (0, 1) and the Youden index. The area under the ROC curve provides a measure of the overall performance of a diagnostic test. In this paper, the author explains how the ROC curve can be used to select optimal cut-off points for a test result, to assess the diagnostic accuracy of a test, and to compare the usefulness of tests. The ROC curve is obtained by calculating the sensitivity and specificity of a test at every possible cut-off point, and plotting sensitivity against 1-specificity. The curve may be used to select optimal cut-off values for a test result, to assess the diagnostic accuracy of a test, and to compare the usefulness of different tests.
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            European Society for Paediatric Endocrinology Consensus Guidelines on Screening, Diagnosis, and Management of Congenital Hypothyroidism

            Objective: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). Evidence: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. Consensus Process: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. Recommendations: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T 4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancy.
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              Congenital hypothyroidism with eutopic thyroid gland: analysis of clinical and biochemical features at diagnosis and after re-evaluation.

              In recent years changes in screening strategies for congenital hypothyroidism (CH) led to an increased detection of mild forms of CH, associated with eutopic thyroid gland. We aimed to determine the clinical evolution of CH with eutopic thyroid gland and to find out prognostic factors at diagnosis and follow-up. We retrospectively analyzed a group of 84 children with CH and eutopic thyroid gland treated at our institution. They all underwent clinical re-evaluation after the age of 3, based on thyroid function testing after l-thyroxine therapy withdrawal, thyroid ultrasonography, and (123)I scintigraphy with perchlorate discharge test. Genetic analysis was performed in selected cases. At re-evaluation, 34.5% of patients showed permanent hypothyroidism and needed l-thyroxine reintroduction, 27.4% had persistent hyperthyrotropinemia (TSH 5-10 mU/L), and 38.1% had transient hypothyroidism. Major risk factors for permanent CH were prematurity, first-degree familial history of goiter/nodules, thyroid hypoplasia at diagnosis, and high l-thyroxine requirements at follow-up. Iodine organification defects were found in 29.7% of patients, 30% of whom harbored DUOX2 mutations. TSH receptor gene mutations were found in 8.7% of patients with persistent thyroid dysfunction and negative perchlorate discharge test. Only one-third of patients with CH and eutopic thyroid gland needed to continue l-thyroxine therapy after re-evaluation. A frequent finding was the persistence of mild hyperthyrotropinemia. The evolution of CH remains difficult to predict, although different clinical features might suggest different outcomes. Mutations in the genes commonly linked to mild forms of CH were documented in a minority of cases.
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                Author and article information

                Journal
                Ann Pediatr Endocrinol Metab
                Ann Pediatr Endocrinol Metab
                APEM
                Annals of Pediatric Endocrinology & Metabolism
                The Korean Society of Pediatric Endocrinology
                2287-1012
                2287-1292
                June 2017
                28 June 2017
                : 22
                : 2
                : 115-118
                Affiliations
                Department of Pediatrics, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea.
                Author notes
                Address for correspondence: Hae Sang Lee, MD, PhD. Department of Pediatrics, Ajou University School of Medicine, 206 World cup-ro, Yeongtong-gu, Suwon 16499, Korea. Tel: +82-31-219-5166, Fax: +82-31-219-5169, seaon98@ 123456naver.com
                Author information
                https://orcid.org/0000-0002-9684-4042
                Article
                10.6065/apem.2017.22.2.115
                5495977
                28690990
                9931a6c0-cd9b-47dc-a991-247c481ec899
                © 2017 Annals of Pediatric Endocrinology & Metabolism

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 October 2016
                : 10 November 2016
                : 20 December 2016
                Categories
                Original Article

                congenital hypothyroidism,thyroid gland,therapeutics

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