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      Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility

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          Abstract

          Thyroid disorders are common, affecting more than 10% of people in the US, and laboratory tests are integral in the management of these conditions. The repertoire of thyroid tests includes blood tests for thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine, thyroglobulin (Tg), thyroglobulin antibodies (Tg-Ab), thyroid peroxidase antibodies (TPO-Ab), TSH receptor antibodies (TRAb), and calcitonin. TSH and free thyroid hormone tests are frequently used to assess the functional status of the thyroid. TPO-Ab and TRAb tests are used to diagnose Hashimoto's thyroiditis and Graves' disease, respectively. Tg and calcitonin are important tumor markers used in the management of differentiated thyroid carcinoma and medullary thyroid carcinoma (MTC), respectively. Procalcitonin may replace calcitonin as a biomarker for MTC. Apart from understanding normal thyroid physiology, it is important to be familiar with the possible pitfalls and caveats in the use of these tests so that they can be interpreted properly and accurately. When results are discordant, clinicians and laboratorians should be mindful of possible assay interferences and/or the effects of concurrent medications. In addition, thyroid function may appear abnormal in the absence of actual thyroid dysfunction during pregnancy and in critical illness. Hence, it is important to consider the clinical context when interpreting results. This review aims to describe the above-mentioned blood tests used in the diagnosis and management of thyroid disorders, as well as the pitfalls in their interpretation. With due knowledge and care, clinicians and laboratorians will be able to fully appreciate the clinical utility of these important laboratory tests.

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          Most cited references80

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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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            The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey.

            The original Whickham Survey documented the prevalence of thyroid disorders in a randomly selected sample of 2779 adults which matched the population of Great Britain in age, sex and social class. The aim of the twenty-year follow-up survey was to determine the incidence and natural history of thyroid disease in this cohort. Subjects were traced at follow-up via the Electoral Register, General Practice registers, Gateshead Family Health Services Authority register and Office of Population Censuses and Surveys. Eight hundred and twenty-five subjects (30% of the sample) had died and, in addition to death certificates, two-thirds had information from either hospital/General Practitioner notes or post-mortem reports to document morbidity prior to death. Of the 1877 known survivors, 96% participated in the follow-up study and 91% were tested for clinical, biochemical and immunological evidence of thyroid dysfunction. Outcomes in terms of morbidity and mortality were determined for over 97% of the original sample. The mean incidence (with 95% confidence intervals) of spontaneous hypothyroidism in women was 3.5/1000 survivors/year (2.8-4.5) rising to 4.1/1000 survivors/year (3.3-5.0) for all causes of hypothyroidism and in men was 0.6/1000 survivors/year (0.3-1.2). The mean incidence of hyperthyroidism in women was 0.8/1000 survivors/year (0.5-1.4) and was negligible in men. Similar incidence rates were calculated for the deceased subjects. An estimate of the probability of the development of hypothyroidism and hyperthyroidism at a particular time, i.e. the hazard rate, showed an increase with age in hypothyroidism but no age relation in hyperthyroidism. The frequency of goitre decreased with age with 10% of women and 2% of men having a goitre at follow-up, as compared to 23% and 5% in the same subjects respectively at the first survey. The presence of a goitre at either survey was not associated with any clinical or biochemical evidence of thyroid dysfunction. In women, an association was found between the development of a goitre and thyroid-antibody status at follow-up, but not initially. The risk of having developed hypothyroidism at follow-up was examined with respect to risk factors identified at first survey. The odds ratios (with 95% confidence intervals) of developing hypothyroidism with (a) raised serum TSH alone were 8 (3-20) for women and 44 (19-104) for men; (b) positive anti-thyroid antibodies alone were 8 (5-15) for women and 25 (10-63) for men; (c) both raised serum TSH and positive anti-thyroid antibodies were 38 (22-65) for women and 173 (81-370) for men. A logit model indicated that increasing values of serum TSH above 2mU/l at first survey increased the probability of developing hypothyroidism which was further increased in the presence of anti-thyroid antibodies. Neither a positive family history of any form of thyroid disease nor parity of women at first survey was associated with increased risk of developing hypothyroidism. Fasting cholesterol and triglyceride levels at first survey when corrected for age showed no association with the development of hypothyroidism in women. This historical cohort study has provided incidence data for thyroid disease over a twenty-year period for a representative cross-sectional sample of the population, and has allowed the determination of the importance of prognostic risk factors for thyroid disease identified twenty years earlier.
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              Non-thyroidal illness in the ICU: a syndrome with different faces.

              Critically ill patients typically present with low or low-normal plasma thyroxine, low plasma triiodothyronine (T3), increased plasma reverse T3 (rT3) concentrations, in the absence of a rise in thyrotropin (TSH). This constellation is referred to as nonthyroidal illness syndrome (NTI). Although it is long known that the severity of NTI is associated with risk of poor outcomes of critical illness, the causality in this association has not been well investigated.

                Author and article information

                Journal
                Ann Lab Med
                Ann Lab Med
                ALM
                Annals of Laboratory Medicine
                The Korean Society for Laboratory Medicine
                2234-3806
                2234-3814
                January 2019
                13 September 2018
                : 39
                : 1
                : 3-14
                Affiliations
                [1 ]Department of Endocrinology, Changi General Hospital, Singapore.
                [2 ]Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
                [3 ]Department of Laboratory Medicine, Changi General Hospital, Singapore.
                Author notes
                Corresponding author: Tar-Choon Aw, FRCPA. Department of Laboratory Medicine, Changi General Hospital, 2 Simei Street 3, Singapore 529889, Singapore. Tel: +65-6850-4927, Fax: +65-6426-9507, tarchoon@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-7814-8836
                Article
                10.3343/alm.2019.39.1.3
                6143469
                30215224
                d3976f7a-0ee3-405f-8e69-71c5adc4c2ea
                © The Korean Society for Laboratory Medicine

                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
                : 21 April 2018
                : 29 May 2018
                : 02 September 2018
                Categories
                Review Article
                Clinical Chemistry

                Clinical chemistry
                thyroid function test,thyroid-stimulating hormone,free thyroxine,free triiodothyronine,thyroglobulin,thyroglobulin antibodies,thyroid peroxidase antibodies,thyroid-stimulating hormone receptor antibodies,calcitonin

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