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

E Mazzaferri, L Braverman, L Wartofsky … (2003)

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.

E Molinaro, A Pinchera, R. Elisei … (2003)

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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Clinical impact of thyroglobulin (Tg) and Tg autoantibody method differences on the management of patients with differentiated thyroid carcinomas.

M Kazarosyan, S Hossein Fatemi, J LoPresti … (2005)

Changes in thyroglobulin (Tg) and/or Tg antibody (TgAb) methods can disrupt the serial monitoring of differentiated thyroid carcinoma (DTC) patients. This study compared Tg measurements made in TgAb-negative and TgAb-positive sera using four RIA and 10 immunometric assay (IMA) methods. TgAb detection using a panel of 12 direct methods was contrasted with four Tg recovery tests. Sera from 110 normal euthyroid subjects (68 TgAb negative/42 TgAb positive) and 131 TgAb-negative DTC patients had Tg and/or TgAb analyses made by 10 laboratories in four countries. Euthyroid controls were used to compare Tg and TgAb ranges, sensitivities, and TgAb interference, whereas DTC patients were used to study Tg assay specificities, hook effects, and the influence of high Tg levels on TgAb measurements. Tg methods had high between-method variability [47 +/- 3% (+/-sem)] that was only marginally reduced by CRM-457 standardization (37 +/- 3%). All methods had suboptimal sensitivity, and some failed to detect Tg in some normal euthyroid controls. Although direct TgAb measurements were more reliable than exogenous recovery tests, TgAb status was only concordant in 65% of sera. Only four of 42 (9.5%) sera containing TgAb had antibody detected by all direct methods. All IMA methods reported paradoxically undetectable Tg for many TgAb-positive euthyroid controls, suggesting TgAb interference, whereas RIA methods reported appropriate normal range values for these same subjects. Some sera displaying interference had TgAb detected by only a minority of methods. Specificity differences, suboptimal sensitivity, hook effects, and an inability to reliably detect interfering TgAb compromise the clinical utility of current Tg and TgAb methods. All of the IMA methods were prone to underestimate serum Tg in the presence of TgAb, whereas the RIA methods appeared resistant to TgAb interference.

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Journal

Journal ID (publisher-id): HRE

Journal ID (nlm-ta): Horm Res Paediatr

Journal ID (doi): 10.1159/issn.1663-2818

Title: Hormone Research in Paediatrics

Publisher: S. Karger AG

ISBN: 978-3-8055-8255-1

ISBN: 978-3-318-01446-4

ISSN (Print): 1663-2818

ISSN (Electronic): 1663-2826

Publication date Subscription-year: 2007

Publication date (Print): February 2007

Publication date (Electronic): 15 February 2007

Volume: 67

Issue: Suppl 1

Pages: 132-142

Affiliations

^aInstitut Gustave Roussy, Villejuif Cédex, France; ^bUniversity of Siena, Siena, Italy

Article

Publisher ID: 97570 Other ID: Horm Res 2007;67:132–142

DOI: 10.1159/000097570

SO-VID: b1ba4271-8b08-449a-bbbc-e8e05b5659bd

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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.

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Area under the curve of TSH after levothyroxine withdrawal versus administration of recombinant human TSH (rhTSH): possible implications for tumor growth
Authors: Pedro Weslley Rosario, Daniela Santos Salles, Saulo Purisch

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

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Most cited references 47

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

Recombinant human thyrotropin-stimulated serum thyroglobulin combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma.

Clinical impact of thyroglobulin (Tg) and Tg autoantibody method differences on the management of patients with differentiated thyroid carcinomas.

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