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      TSH Measurement and Its Implications for Personalised Clinical Decision-Making

      review-article
      1 , * , 2
      Journal of Thyroid Research
      Hindawi Publishing Corporation

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          Abstract

          Advances in assay technology have promoted thyrotropin (TSH) measurements from participation in a multi-analyte assessment of thyroid function to a statistically defined screening parameter in its own right. While this approach has been successful in many ways, it has some grave limitations. This includes the basic question of what constitutes an agreed reference range and the fact that the population-based reference range by far exceeds the variation of the intraindividual set point. Both problems result in a potential misdiagnosis of normal and pathological thyroid function in a substantial proportion of patients. From a physiological perspective, TSH plays an integrated role in thyroid homeostasis. Few attempts have been made to adopt physiological insights into thyroid homeostasis for medical decision-making. Some emerging novel findings question the widely assumed log-linear TSH-FT 4 relationship over the entire thyroid function spectrum. This data favours more complex hierarchically structured models. With a better understanding of its role in thyroid homeostasis in thyroid health and disease, TSH can be revisited in the context of thyroid regulation. This, in turn, could help overcome some of the limitations arising from its isolated statistical use and offer new prospects towards a more personalised interpretation of thyroid test results.

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          Most cited references82

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          Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline.

          The aim was to update the guidelines for the management of thyroid dysfunction during pregnancy and postpartum published previously in 2007. A summary of changes between the 2007 and 2012 version is identified in the Supplemental Data (published on The Endocrine Society's Journals Online web site at http://jcem.endojournals.org). This evidence-based guideline was developed according to the U.S. Preventive Service Task Force, grading items level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms) as well as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The guideline was developed through a series of e-mails, conference calls, and one face-to-face meeting. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocrine Society, Asia and Oceania Thyroid Association, and the Latin American Thyroid Society. A second draft was reviewed and approved by The Endocrine Society Council. At each stage of review, the Task Force received written comments and incorporated substantive changes. Practice guidelines are presented for diagnosis and treatment of patients with thyroid-related medical issues just before and during pregnancy and in the postpartum interval. These include evidence-based approaches to assessing the cause of the condition, treating it, and managing hypothyroidism, hyperthyroidism, gestational hyperthyroidism, thyroid autoimmunity, thyroid tumors, iodine nutrition, postpartum thyroiditis, and screening for thyroid disease. Indications and side effects of therapeutic agents used in treatment are also presented.
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            Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association.

            Hypothyroidism has multiple etiologies and manifestations. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions. This paper describes evidence-based clinical guidelines for the clinical management of hypothyroidism in ambulatory patients. The development of these guidelines was commissioned by the American Association of Clinical Endocrinologists (AACE) in association with American Thyroid Association (ATA). AACE and the ATA assembled a task force of expert clinicians who authored this article. The authors examined relevant literature and took an evidence-based medicine approach that incorporated their knowledge and experience to develop a series of specific recommendations and the rationale for these recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach outlined in the American Association of Clinical Endocrinologists Protocol for Standardized Production of Clinical Guidelines-2010 update. Topics addressed include the etiology, epidemiology, clinical and laboratory evaluation, management, and consequences of hypothyroidism. Screening, treatment of subclinical hypothyroidism, pregnancy, and areas for future research are also covered. Fifty-two evidence-based recommendations and subrecommendations were developed to aid in the care of patients with hypothyroidism and to share what the authors believe is current, rational, and optimal medical practice for the diagnosis and care of hypothyroidism. A serum thyrotropin is the single best screening test for primary thyroid dysfunction for the vast majority of outpatient clinical situations. The standard treatment is replacement with L-thyroxine. The decision to treat subclinical hypothyroidism when the serum thyrotropin is less than 10 mIU/L should be tailored to the individual patient.
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              Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism.

              Measurements from all age groups defined the upper limit of the TSH reference range in National Health and Nutrition Examination Survey III. The TSH median, 97.5 centile and prevalence of subclinical hypothyroidism (SCH), normal serum T(4) and TSH greater than 4.5 mIU/liter, increased progressively with age. Age-adjusted reference ranges would include many people with TSH greater than 4.5 mIU/liter. We determined whether increasing 50 and 97.5 centiles with age resulted from more patients with SCH in populations with normal TSH distribution or whether age-specific population shifts to higher serum TSH might account for these findings. We analyzed TSH, antithyroid antibodies, and TSH frequency distribution curves for specific age deciles in populations without thyroid disease, with or without antithyroid antibodies. Without thyroid disease, 10.6% of 20- to 29-yr-olds had TSH greater than 2.5 mIU/liter, increasing to 40% in the 80+ group, 14.5% of whom had TSH greater than 4.5 mIU/liter. When TSH was greater than 4.5 mIU/liter, the percentage with antibodies was 67.4% (age 40-49 yr) and progressively decreased to 40.5% in the 80+ group. TSH frequency distribution curves of the 80+ group with or without antibodies was displaced to higher TSH, including TSH at peak frequency. The 97.5 centiles for the 20-29 and 80+ groups were 3.56 and 7.49 mIU/liter, respectively. Seventy percent of older patients with TSH greater than 4.5 mIU/liter were within their age-specific reference range. TSH distribution progressively shifts toward higher concentrations with age. The prevalence of SCH may be significantly overestimated unless an age-specific range for TSH is used.
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                Author and article information

                Journal
                J Thyroid Res
                J Thyroid Res
                JTR
                Journal of Thyroid Research
                Hindawi Publishing Corporation
                2090-8067
                2042-0072
                2012
                9 December 2012
                : 2012
                : 438037
                Affiliations
                1Department of Nuclear Medicine, Klinikum Luedenscheid, Paulmannshoeherstraße 14, 58515 Luedenscheid, Germany
                2Consultancy Division, North Lakes Clinical, 6 High Wheatley, Ilkley, West Yorkshire LS29 8RX, UK
                Author notes

                Academic Editor: Johannes W. Dietrich

                Author information
                http://orcid.org/0000-0002-1326-4270
                Article
                10.1155/2012/438037
                3529417
                23304636
                5edb4ac9-325c-4025-a1f2-af513fac8763
                Copyright © 2012 R. Hoermann and J. E. M. Midgley.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 October 2012
                : 15 November 2012
                Categories
                Review Article

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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