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      Malignancy risk of hyperfunctioning thyroid nodules compared with non-toxic nodules: systematic review and a meta-analysis

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          Abstract

          Background

          Hyperfunctioning or hot nodules are thought to be rarely malignant. As such, current guidelines recommend that hot nodules be excluded from further malignancy risk stratification. The objective of this systematic review and meta-analysis is to compare the malignancy risk in hot nodules and non-toxic nodules in observational studies.

          Methods

          Ovid MEDLINE Daily and Ovid MEDLINE, EMBASE, Scopus, and Web of Science databases were searched. Observational studies which met all of the following were included: (1) use thyroid scintigraphy for nodule assessment, (2) inclusion of both hyperfunctioning and non-functioning nodules based on scintigraphy, (3) available postoperative histopathologic nodule results, (4) published up to November 12, 2020 in either English or French. The following data was extracted: malignancy outcomes include malignancy rate, mapping of the carcinoma within the hot nodule, inclusion of microcarcinomas, and presence of gene mutations.

          Results

          Among the seven included studies, overall incidence of malignancy in all hot thyroid nodules ranged from 5 to 100% in comparison with non-toxic nodules, 3.8–46%. Odds of malignancy were also compared between hot and non-toxic thyroid nodules, separated into solitary nodules, multiple nodules and combination of the two. Pooled odds ratio (OR) of solitary thyroid nodules revealed a single hot nodule OR of 0.38 (95% confidence interval (CI) 0.25, 0.59), toxic multinodular goiter OR of 0.51 (95% CI 0.34, 0.75), and a combined hot nodule OR of 0.45 (95% CI 0.31, 0.65). The odds of malignancy are reduced by 55% in hot nodules; however, the incidence was not zero.

          Conclusions

          Odds of malignancy of hot nodules is reduced compared with non-toxic nodules; however, the incidence of malignancy reported in hot nodules was higher than expected. These findings highlight the need for further studies into the malignancy risk of hot nodules.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13044-021-00094-1.

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          Most cited references95

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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            Quantifying heterogeneity in a meta-analysis.

            The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity. Copyright 2002 John Wiley & Sons, Ltd.
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              2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

              Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer.
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                Author and article information

                Contributors
                ralf.paschke@ucalgary.ca
                Journal
                Thyroid Res
                Thyroid Res
                Thyroid Research
                BioMed Central (London )
                1756-6614
                25 February 2021
                25 February 2021
                2021
                : 14
                : 3
                Affiliations
                [1 ]GRID grid.22072.35, ISNI 0000 0004 1936 7697, Department of Medicine, Cumming School of Medicine, , University of Calgary, ; Calgary, Canada
                [2 ]GRID grid.22072.35, ISNI 0000 0004 1936 7697, Section of Endocrinology and Metabolism, Department of Medicine, Cumming School of Medicine, , University of Calgary, ; Calgary, Canada
                [3 ]GRID grid.22072.35, ISNI 0000 0004 1936 7697, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, , University of Calgary, ; Calgary, AB Canada
                [4 ]GRID grid.22072.35, ISNI 0000 0004 1936 7697, Clinical Medicine. Health Sciences Library, , University of Calgary, ; Calgary, Canada
                [5 ]GRID grid.22072.35, ISNI 0000 0004 1936 7697, Department of Community Health Sciences, Cumming School of Medicine, , University of Calgary, ; Calgary, AB Canada
                [6 ]GRID grid.22072.35, ISNI 0000 0004 1936 7697, Departments of Oncology, Pathology, and Laboratory Medicine, Biochemistry and Molecular Biology, Cumming School of Medicine, , University of Calgary, ; Calgary, Canada
                Author information
                http://orcid.org/0000-0003-1470-268X
                Article
                94
                10.1186/s13044-021-00094-1
                7905613
                33632297
                fc7aad9f-973a-409d-9811-8c9f39b6856d
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 10 September 2020
                : 1 February 2021
                Categories
                Research
                Custom metadata
                © The Author(s) 2021

                Endocrinology & Diabetes
                thyroid nodules,malignancy,hot nodule,thyrotoxicosis,thyroid cancer
                Endocrinology & Diabetes
                thyroid nodules, malignancy, hot nodule, thyrotoxicosis, thyroid cancer

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