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      A systematic review of subclinical hyperthyroidism guidelines: a remarkable range of recommendations

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          Abstract

          Background

          Subclinical thyroid diseases are often the subject of debate concerning their clinical significance, the appropriateness of diagnostic testing, and possible treatment. This systematic review addresses the variation in international guidelines for subclinical hyperthyroidism, focusing on diagnostic workup, treatment, and follow-up recommendations.

          Methods

          Following the PRISMA guidelines, we searched PubMed, Embase, and guideline-specific databases and included clinical practice guidelines with recommendations on subclinical hyperthyroidism. Guideline recommendations were extracted, and quality assessment was performed using selected questions of the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument.

          Results

          Of the 2624 records screened, 22 guidelines were included, which were published between 2007 and 2021. Guideline quality was generally intermediate to low. Diagnostic approaches differed substantially, particularly in the extent of recommended testing. Treatment initiation depended on TSH levels, age, and comorbidities, but the level of detail regarding defining precise comorbidities varied. Recommendations for monitoring intervals for follow-up ranged from 3 to 12 months.

          Conclusion

          This review underscores the existing variability in (inter)national guidelines concerning subclinical hyperthyroidism. There isa need for clear recommendations in guidelines considering diagnostic workup, treatment, and follow-up of subclinical hyperthyroidism. In order to establish this, future research should focus on determining clear and evidence-based intervention thresholds.

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          Most cited references33

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          AGREE II: advancing guideline development, reporting and evaluation in health care.

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            2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis.

            Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This document describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspecialty physicians and others providing care for patients with this condition.
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              2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism

              Graves’ disease (GD) is a systemic autoimmune disorder characterized by the infiltration of thyroid antigen-specific T cells into thyroid-stimulating hormone receptor (TSH-R)-expressing tissues. Stimulatory autoantibodies (Ab) in GD activate the TSH-R leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with biochemically confirmed thyrotoxicosis, positive TSH-R-Ab, a hypervascular and hypoechoic thyroid gland (ultrasound), and associated orbitopathy. In GD, measurement of TSH-R-Ab is recommended for an accurate diagnosis/differential diagnosis, prior to stopping antithyroid drug (ATD) treatment and during pregnancy. Graves’ hyperthyroidism is treated by decreasing thyroid hormone synthesis with the use of ATD, or by reducing the amount of thyroid tissue with radioactive iodine (RAI) treatment or total thyroidectomy. Patients with newly diagnosed Graves’ hyperthyroidism are usually medically treated for 12–18 months with methimazole (MMI) as the preferred drug. In children with GD, a 24- to 36-month course of MMI is recommended. Patients with persistently high TSH-R-Ab at 12–18 months can continue MMI treatment, repeating the TSH-R-Ab measurement after an additional 12 months, or opt for therapy with RAI or thyroidectomy. Women treated with MMI should be switched to propylthiouracil when planning pregnancy and during the first trimester of pregnancy. If a patient relapses after completing a course of ATD, definitive treatment is recommended; however, continued long-term low-dose MMI can be considered. Thyroidectomy should be performed by an experienced high-volume thyroid surgeon. RAI is contraindicated in Graves’ patients with active/severe orbitopathy, and steroid prophylaxis is warranted in Graves’ patients with mild/active orbitopathy receiving RAI.

                Author and article information

                Journal
                Eur Thyroid J
                Eur Thyroid J
                ETJ
                European Thyroid Journal
                Bioscientifica Ltd (Bristol )
                2235-0640
                2235-0802
                13 June 2024
                17 May 2024
                01 June 2024
                : 13
                : 3
                : e240036
                Affiliations
                [1 ]Department of Laboratory Medicine , Endocrine Laboratory, Amsterdam UMC Location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
                [2 ]Amsterdam Gastroenterology , Endocrinology & Metabolism, Amsterdam, The Netherlands
                [3 ]Amsterdam Reproduction & Development Research Institute , Amsterdam, The Netherlands
                [4 ]Department of Endocrinology and Metabolism , Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
                [5 ]Department of General Practice , Amsterdam UMC Location Vrije Universiteit, Amsterdam, The Netherlands
                [6 ]Amsterdam Public Health Research Institute , Amsterdam UMC, The Netherlands
                [7 ]LUMC Center for Medicine for Older People , Leiden University Medical Center, Leiden, The Netherlands
                [8 ]Department of Public Health and Primary Care , Leiden University Medical Center, Leiden, The Netherlands
                [9 ]Department of Laboratory Medicine , Endocrine Laboratory, Amsterdam UMC Location Vrije Universiteit Amsterdam, Boelelaan, Amsterdam, The Netherlands
                [10 ]Laboratory Specialized Diagnostics & Research , Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
                [11 ]Amsterdam Public Health Research Institute , Meibergdreef, Amsterdam, The Netherlands
                Author notes
                Correspondence should be addressed to A C Heijboer: a.heijboer@ 123456amsterdamumc.nl
                Author information
                http://orcid.org/0000-0001-9989-0821
                http://orcid.org/0000-0002-4994-2918
                http://orcid.org/0000-0001-6466-8497
                http://orcid.org/0000-0002-6712-9955
                Article
                ETJ-24-0036
                10.1530/ETJ-24-0036
                11227059
                38758966
                025a85e4-9b04-45d1-a3a5-50ccbb0d25c2
                © the author(s)

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

                History
                : 08 February 2024
                : 17 May 2024
                Categories
                Systematic Review
                ETJ-hyperthyroidism-thyrotoxicosis, Hyperthyroidism and thyrotoxicosis
                Custom metadata
                ETJ-hyperthyroidism-thyrotoxicosis

                subclinical hyperthyroidism,clinical practice guideline,guideline,systematic review,thyroid,primary care,general practice

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