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      Recombinant Human Thyroid-Stimulating Hormone: Use in Papillary and Follicular Thyroid Cancer

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          Abstract

          Recombinant human thyroid-stimulating hormone (rhTSH) is used in thyroid cancer patients to prepare for postoperative administration of 3.7 GBq of radioiodine (<sup>131</sup>I) and to facilitate the determination of serum thyroglobulin during follow-up. Recombinant human TSH is also used during thyroxine treatment to avoid the hypothyroid state induced by prolonged thyroid hormone withdrawal and thereby maintains a patient’s quality of life.

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          Most cited references 47

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          A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma.

          Recent studies have provided new information regarding the optimal surveillance protocols for low-risk patients with differentiated thyroid cancer (DTC). This article summarizes the main issues brought out in a consensus conference of thyroid cancer specialists who analyzed and discussed this new data. There is growing recognition of the value of serum thyroglobulin (Tg) as part of routine surveillance. An undetectable serum Tg measured during thyroid hormone suppression of TSH (THST) is often misleading. Eight studies show that 21% of 784 patients who had no clinical evidence of tumor with baseline serum Tg levels usually below 1 micro g/liter during THST had, in response to recombinant human TSH (rhTSH), a rise in serum Tg to more than 2 micro g/liter. When this happened, 36% of the patients were found to have metastases (36% at distant sites) that were identified in 91% by an rhTSH-stimulated Tg above 2 micro g/liter. Diagnostic whole body scanning, after either rhTSH or thyroid hormone withdrawal, identified only 19% of the cases of metastases. Ten studies comprising 1599 patients demonstrate that a TSH-stimulated Tg test using a Tg cutoff of 2 micro g/liter (either after thyroid hormone withdrawal or 72 h after rhTSH) is sufficiently sensitive to be used as the principal test in the follow-up management of low-risk patients with DTC and that the routine use of diagnostic whole body scanning in follow-up should be discouraged. On the basis of the foregoing, we propose a surveillance guideline using TSH-stimulated Tg levels for patients who have undergone total or near-total thyroidectomy and (131)I ablation for DTC and have no clinical evidence of residual tumor with a serum Tg below 1 micro g/liter during THST.
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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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              Diagnosis of neck recurrences in patients with differentiated thyroid carcinoma.

              The follow-up of patients with differentiated thyroid carcinoma (DTC) is traditionally carried out with (131)I whole body scan ((131)I WBS) and serum thyroglobulin (Tg) measurement. Neck ultrasonography (US) is also used. We compared the roles of Tg measurement (IRMA assay) after l-thyroxine (T4) withdrawal, (131)I WBS, and US in the diagnosis of DTC neck recurrences. Diagnosis of DTC neck recurrences was based on fine-needle aspiration biopsy (FNAB) or on histologic results. Four hundred ninety-four DTC patients (120 males, 374 females; mean age, 49.3 years), submitted to total thyroidectomy and subsequent radioablative (131)I treatment, underwent serum Tg measurement off T4 therapy, (131)I WBS, and neck US at our institution. Mean (+/- SD) follow-up time was 55.1 +/- 37.7 months. Neck DTC recurrences were detected in 51 (10.3%) patients (34 females, 17 males; mean age, 49.5 years). Neck recurrences occurred after 44.6 +/- 21.4 months from initial treatment. Serum Tg levels increased (> or = 2 ng/mL) off T4 therapy in 29 patients (sensitivity 56.8%), (131)I WBS showed neck uptake in 23 patients (sensitivity 45.1%) and coexisting distant metastases were detected in 9 of 23 patients, and US identified neck recurrence in 48 patients (sensitivity 94.1%). Of these 48 neck recurrences, 19 were found in the laterocervical compartment and 29 in the central neck compartment. Traditional techniques for the surveillance of DTC patients are not as sensitive as US in the detection of neck recurrences. Neck US detects recurrences in patients with undetectable serum Tg levels and negative IWBS and should be performed as the first-line test in the follow-up of all DTC patients. Copyright 2003 American Cancer Society.
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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                978-3-8055-8255-1
                978-3-318-01446-4
                1663-2818
                1663-2826
                2007
                February 2007
                15 February 2007
                : 67
                : Suppl 1
                : 132-142
                Affiliations
                aInstitut Gustave Roussy, Villejuif Cédex, France; bUniversity of Siena, Siena, Italy
                Article
                97570 Horm Res 2007;67:132–142
                10.1159/000097570
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                References: 87, Pages: 11
                Categories
                Adult Workshop 1

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