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      The Cut-Off Level of Recombinant Human TSH-Stimulated Thyroglobulin in the Follow-Up of Patients with Differentiated Thyroid Cancer

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          Abstract

          Background

          The treatment of differentiated thyroid cancer (DTC) ends in full recovery in 80% of cases. However, in 20% of cases local recurrences or distant metastases are observed, for this reason DTC patients are under life-long follow-up. The most sensitive marker for recurrence is stimulated thyroglobulin (Tg) which, together with neck ultrasound (US), enables correct diagnosis in nearly all cases of the active disease. For many years the only known stimulation was a 4–5 week withdrawal from the L-T4 therapy (THW). For the last couple of years stimulation with the use of recombinant human TSH (rhTSH) has been available. This method of stimulation may have a significant influence in obtaining the Tg level. However, it is important to determine the cut-off level for rhTSH-stimulated Tg (rhTSH/Tg).

          Materials and Methods

          This is a retrospective analysis of consecutive patients from one facility who have qualified over a period of two years for repeated radioiodine therapy (RIA). In our facility the ablation effectiveness evaluation is always carried out with the use of rhTSH, with the repeated therapy following THW. Such a procedure enables two Tg measurements in the same patient after both types of stimulation within 4–5 weeks. The obtained values were compared, cut-off levels in THW conditions were used (2.0 ng/ml for patients in remission and 10.0 ng/ml for patients with an active disease). In order to determine the cut-off level for rhTSH/Tg, regression analysis and ROC curves were used.

          Results

          In 63 patients the Tg measurement of both methods of stimulation were obtained. It was observed that there was a high correlation between rhTSH/Tg and THW/Tg. However, the rhTSH/Tg level was significantly lower than THW/ Tg. The rhTSH/ Tg cut-off levels which corresponded to the 2.0 ng/ml and 10.0 ng/ml limits for THW/Tg were calculated and the values were 0.6 ng/ml and 2.3 ng/ml respectively.

          Conclusions

          The method of stimulation has a significant impact on the obtained Tg concentrations. The assumed THW/Tg cut off levels must not be transferred to rhTSH/Tg.

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          Most cited references11

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          Thyroid cancer epidemiology and prognostic variables.

          Thyroid cancer comprises a broad spectrum of diseases with variable prognoses. Although most patients with this disease have excellent overall survival, there are some who do not fare so well. With the worldwide increase in incidence, the need to identify which tumours pose the greatest risk to patients is more acute than ever. This paper will discuss this rising trend in incidence with an analysis of the possible reasons for the increase. In addition, the paper will explore the factors that portend a worse prognosis for the individual patient. Finally, the limitations of the current staging systems will be discussed, with particular emphasis on why they are not as informative in the management of patients with thyroid cancer. Copyright (c) 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
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            Recombinant human thyrotropin-stimulated serum thyroglobulin combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma.

            Recombinant human TSH (rhTSH)-stimulated thyroglobulin (Tg) measurement and (131)I whole body scan (WBS) have been validated as informative tests in the postsurgical follow-up of differentiated thyroid carcinoma. We report the diagnostic accuracy of Tg measurement and diagnostic WBS, alone or in combination, after rhTSH stimulation in a retrospective, consecutive series of patients undergoing follow-up for differentiated thyroid cancer. Routine procedures also include neck ultrasound in every patient and post-therapy WBS when indicated. We studied 340 consecutive patients with differentiated thyroid carcinoma, previously treated with near-total thyroidectomy and (131)I thyroid ablation, scheduled for routine diagnostic tests. At baseline on L-T(4)-suppressive therapy, 294 patients had undetectable (<1 ng/ml) serum Tg and negative anti-Tg autoantibodies (TgAb), 25 patients had undetectable serum Tg and positive TgAb, and 21 patients had detectable serum Tg and negative TgAb. These patients were tested for the presence of active disease by rhTSH stimulation. The results of our study showed that rhTSH-stimulated Tg alone had a diagnostic sensitivity of 85% for detecting active disease and a negative predictive value (NPV) of 98.2%. After adding the results of neck ultrasound, sensitivity increased to 96.3%, and the NPV to 99.5%. rhTSH-stimulated WBS had a sensitivity of only 21% and a NPV of 89%. The combination of rhTSH-stimulated Tg and WBS had a sensitivity of 92.7% and a NPV of 99%. We conclude that the rhTSH-stimulated Tg test combined with neck ultrasonography has the highest diagnostic accuracy in detecting persistent disease in the follow-up of differentiated thyroid carcinoma. A detectable level of serum Tg on L-T(4), its conversion from undetectable to detectable after rhTSH, and/or a suspicious finding at ultrasound will allow the identification of patients requiring therapeutic procedures without the need for diagnostic WBS.
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              American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules: executive summary of recommendations.

              American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules are systematically developed statements to assist health care professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                31 July 2015
                2015
                : 10
                : 7
                : e0133852
                Affiliations
                [1 ]Endocrinology Department, Holycross Cancer Centre, Kielce, Poland
                [2 ]Laboratory of Tumor Markers, Holycross Cancer Centre, Kielce, Poland
                [3 ]Clinical Oncology Department, Holycross Cancer Centre, Kielce, Poland
                Medical University of Gdańsk, POLAND
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AK. Performed the experiments: AS IP DGP TT AW. Analyzed the data: AK RM. Contributed reagents/materials/analysis tools: AS IP DGP TT AW SG. Wrote the paper: AK SG.

                Article
                PONE-D-15-17781
                10.1371/journal.pone.0133852
                4521804
                26230494
                02b2d558-b9c3-468f-9c37-6195ab3eba7c
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 28 April 2015
                : 3 July 2015
                Page count
                Figures: 3, Tables: 3, Pages: 9
                Funding
                The study was funded by Holycross Cancer Centre.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper.

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