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Iscan Y, Sengun B, Karatas I, Atalay HB, Sormaz IC, Onder S, Yegen G, Hacisahinogullari H, Tunca F, Giles Senyurek Y. The impact of intraoperative neural monitoring during papillary thyroid cancer surgery on completeness of thyroidectomy and thyroglobulin response: a propensity-score matched study. Acta Chir Belg 2024; 124:298-306. [PMID: 38206297 DOI: 10.1080/00015458.2024.2305501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Accepted: 01/09/2024] [Indexed: 01/12/2024]
Abstract
BACKGROUND Intraoperative neural monitoring (IONM) has been utilized for a variety of thyroid pathologies, including papillary thyroid carcinoma (PTC). Remnant thyroid tissue following total thyroidectomy (TT) in patients with PTC is associated with increased recurrence. The aim of this study is to investigate whether the use of IONM in PTC surgery has an impact on the completeness of thyroidectomy. METHODS Retrospectively, patients with preoperative diagnosis of PTC, who underwent TT in a tertiary center were reviewed. They were grouped based on the IONM usage, and 1:1 propensity-score match was performed. Primary outcome was the completeness of thyroidectomy, determined by measuring postoperative stimulated thyroglobulin levels (sTg). RESULTS Among 274 clinically node-negative PTC patients who underwent TT and ipsilateral prophylactic central lymph-node dissection, a total of 170 patients (85:85) were matched. Postoperative sTg levels were significantly lower in the IONM group (1 ng/dL vs. 0.4 ng/dL; p < 0.01) with higher percentage of the patients with sTg levels <1 ng/ml (50.6% vs. 69.4%; p = 0.01). More patients in the no-IONM group received RAI ablation with significantly higher doses (mean mci: 120 vs. 102; p = 0.02). CONCLUSION The use of IONM during thyroidectomy provides improvement in the completeness of thyroidectomy and reduction in postoperative sTg levels which can be used as a guide by clinicians to avoid RAI ablation in selected PTC patients and to adjust low ablative doses in patients who are scheduled for remnant ablation.
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Affiliation(s)
- Yalin Iscan
- Faculty of Medicine, Department of General Surgery, Istanbul University, Istanbul, Turkey
| | - Berke Sengun
- Faculty of Medicine, Department of General Surgery, Istanbul University, Istanbul, Turkey
| | - Irem Karatas
- Faculty of Medicine, Department of General Surgery, Istanbul University, Istanbul, Turkey
| | - Hasan Berke Atalay
- Faculty of Medicine, Department of General Surgery, Istanbul University, Istanbul, Turkey
| | - Ismail Cem Sormaz
- Faculty of Medicine, Department of General Surgery, Istanbul University, Istanbul, Turkey
| | - Semen Onder
- Faculty of Medicine, Department of Pathology, Istanbul University, Istanbul, Turkey
| | - Gulcin Yegen
- Faculty of Medicine, Department of Pathology, Istanbul University, Istanbul, Turkey
| | - Hulya Hacisahinogullari
- Faculty of Medicine, Department of Internal Medicine, Division of Endocrinology, Istanbul University, Istanbul, Turkey
| | - Fatih Tunca
- Faculty of Medicine, Department of General Surgery, Istanbul University, Istanbul, Turkey
| | - Yasemin Giles Senyurek
- Faculty of Medicine, Department of General Surgery, Istanbul University, Istanbul, Turkey
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Added Value of Postoperative Radioiodine Scan for Staging and Risk Stratification in Papillary Thyroid Microcarcinoma. J ASEAN Fed Endocr Soc 2021; 36:64-68. [PMID: 34177090 PMCID: PMC8214359 DOI: 10.15605/jafes.036.01.10] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 03/30/2021] [Indexed: 11/17/2022] Open
Abstract
Objective The complete staging and risk stratification of Papillary thyroid microcarcinoma (PTMC) is usually not done due to its theoretically low recurrence rates. This study aimed to determine the value of postoperative radioiodine diagnostic scan and SPECT/CT for the accurate staging and risk stratification in PTMC patients. Methodology This study was a retrospective review of PTMC patients from January 2014 to May 2017 who underwent I-131 scans. All PTMC patients were initially staged by the 8th edition AJCC/TNM staging system and risk-stratified, based on clinical information, histopathology and stimulated thyroglobulin (sTg). After I-131 scan, staging and risk stratification were re-assessed. The proportion of patients who ended up with a higher stage and risk stratification were reported. Results and Conclusion Fifty-two patients were included. The overall upgrading of cancer stage was 7.7 %. The overall higher risk stratification was 19.2% with radioiodine-avid lymph node, lung, and bone metastases. Neck and paratracheal node metastases were found in 37.3% of the initial low-risk patients with sTg less than 5 ng/mL. Lung metastasis was found in the initial intermediate-risk patient. The I-131 scan helps to localize metastatic lesions and results in a higher stage in 50% of the initial high-risk patients. This study provides some evidence showing the value of postoperative radioiodine WBS for accurate staging and risk stratification in PTMC patients. Larger studies with analytical design should be further performed to prove its significant utility.
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Jammah AA, Masood A, Akkielah LA, Alhaddad S, Alhaddad MA, Alharbi M, Alguwaihes A, Alzahrani S. Utility of Stimulated Thyroglobulin in Reclassifying Low Risk Thyroid Cancer Patients' Following Thyroidectomy and Radioactive Iodine Ablation: A 7-Year Prospective Trial. Front Endocrinol (Lausanne) 2021; 11:603432. [PMID: 33716951 PMCID: PMC7945948 DOI: 10.3389/fendo.2020.603432] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Accepted: 12/30/2020] [Indexed: 11/16/2022] Open
Abstract
Context Following total thyroidectomy and radioactive iodine (RAI) ablation, serum thyroglobulin levels should be undetectable to assure that patients are excellent responders and at very low risk of recurrence. Objective To assess the utility of stimulated (sTg) and non-stimulated (nsTg) thyroglobulin levels in prediction of patients outcomes with differentiated thyroid cancer (DTC) following total thyroidectomy and RAI ablation. Method A prospective observational study conducted at a University Hospital in Saudi Arabia. Patients diagnosed with differentiated thyroid cancer and were post total thyroidectomy and RAI ablation. Thyroglobulin levels (nsTg and sTg) were estimated 3-6 months post-RAI. Patients with nsTg <2 ng/ml were stratified based on their levels and were followed-up for 5 years and clinical responses were measured. Results Of 196 patients, nsTg levels were <0.1 ng/ml in 122 (62%) patients and 0.1-2.0 ng/ml in 74 (38%). Of 122 patients with nsTg <0.1 ng/ml, 120 (98%) had sTg levels <1 ng/ml, with no structural or functional disease. sTg levels >1 occurred in 26 (35%) of patients with nsTg 0.1-2.0 ng/ml, 11 (15%) had structural incomplete response. None of the patients with sTg levels <1 ng/ml developed structural or functional disease over the follow-up period. Conclusion Suppressed thyroglobulin (nsTg < 0.1 ng/ml) indicates a very low risk of recurrence that does not require stimulation. Stimulated thyroglobulin is beneficial with nsTg 0.1-2 ng/ml for re-classifying patients and estimating their risk for incomplete responses over a 7 years follow-up period.
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Affiliation(s)
- Anwar A. Jammah
- Department of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Afshan Masood
- Obesity Research Center, King Saud University, Riyadh, Saudi Arabia
| | | | - Shaimaa Alhaddad
- Department of Medicine, Endocrinology Division, Ministry of Health, Kuwait City, Kuwait
| | - Maath A. Alhaddad
- Faculty of Allied Health Sciences, Kuwait University, Kuwait City, Kuwait
| | - Mariam Alharbi
- Endocrine and Internal Medicine Department, Qassim University, Buraydah, Saudi Arabia
| | | | - Saad Alzahrani
- Obesity, Endocrine, and Metabolism Center, King Fahad Medical City, Riyadh, Saudi Arabia
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Wheeler SE, Liu L, Blair HC, Sivak R, Longo N, Tischler J, Mulvey K, Palmer OMP. Clinical laboratory verification of thyroglobulin concentrations in the presence of autoantibodies to thyroglobulin: comparison of EIA, radioimmunoassay and LC MS/MS measurements in an Urban Hospital. BMC Res Notes 2017; 10:725. [PMID: 29221487 PMCID: PMC5723050 DOI: 10.1186/s13104-017-3050-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Accepted: 11/30/2017] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE Thyroglobulin (Tg) measurements assess recurrence in post-thyroidectomy thyroid cancer patients. Tg measurements by enzyme immunoassays (EIA) can be falsely elevated by interference from Tg autoantibodies (TgAb). Radioimmunoassay (RIA) is less susceptible to TgAb interference and has been the standard-of-care test for TgAb positive patients. Recently developed liquid chromatography tandem mass spectrometry (LC-MS/MS) methods may eliminate TgAb interference. We assessed the performance of Tg measurements by EIA, RIA and LC-MS/MS to evaluate TgAb interference differences. RESULTS We measured TgAb and Tg in 50 plasma samples from 40 patients in whom Tg measurement was part of their routine follow-up and 10 healthy volunteers. Discrepancy between EIA and both LC-MS/MS and RIA was observed at low Tg concentrations (≤ 7.55 ng/mL) in TgAb positive specimens (LC-MS/MS = 1.9 * EIA - 0.03, r = 0.68). RIA and LC-MS/MS Tg measurements in TgAb positive specimens with low Tg concentrations had improved correlation but demonstrated bias (LC MS/MS = 0.6 * RIA - 1.4, r = 0.90). Disagreement between methods may be attributed to LC-MS/MS reported Tg concentrations as undetectable compared to RIA. It seems likely that most discrepant cases are falsely elevated in RIA due to TgAb interference, however, some cases appear below the detection limit of LC-MS/MS; implementation of LC-MS/MS by clinicians will require lower detection limits.
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Affiliation(s)
- Sarah E Wheeler
- Department of Pathology, University of Pittsburgh School of Medicine, S723 Scaife Hall, 3550 Terrace St, Pittsburgh, PA, 15261, USA
| | - Li Liu
- Department of Pathology, University of Pittsburgh School of Medicine, S723 Scaife Hall, 3550 Terrace St, Pittsburgh, PA, 15261, USA
| | - Harry C Blair
- Department of Pathology, University of Pittsburgh School of Medicine, S723 Scaife Hall, 3550 Terrace St, Pittsburgh, PA, 15261, USA.,University of Pittsburgh Medical Center (UPMC), Clinical Laboratory Building, 3477 Euler Way, Room 3014, Pittsburgh, PA, 15213, USA
| | - Richard Sivak
- University of Pittsburgh Medical Center (UPMC), Clinical Laboratory Building, 3477 Euler Way, Room 3014, Pittsburgh, PA, 15213, USA
| | - Nancy Longo
- University of Pittsburgh Medical Center (UPMC), Clinical Laboratory Building, 3477 Euler Way, Room 3014, Pittsburgh, PA, 15213, USA
| | - Jeffery Tischler
- University of Pittsburgh Medical Center (UPMC), Clinical Laboratory Building, 3477 Euler Way, Room 3014, Pittsburgh, PA, 15213, USA
| | - Kathryn Mulvey
- University of Pittsburgh Medical Center (UPMC), Clinical Laboratory Building, 3477 Euler Way, Room 3014, Pittsburgh, PA, 15213, USA
| | - Octavia M Peck Palmer
- Department of Pathology, University of Pittsburgh School of Medicine, S723 Scaife Hall, 3550 Terrace St, Pittsburgh, PA, 15261, USA. .,University of Pittsburgh Medical Center (UPMC), Clinical Laboratory Building, 3477 Euler Way, Room 3014, Pittsburgh, PA, 15213, USA. .,Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA. .,Department of Clinical and Translational Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
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Indrasena BSH. Use of thyroglobulin as a tumour marker. World J Biol Chem 2017; 8:81-85. [PMID: 28289520 PMCID: PMC5329716 DOI: 10.4331/wjbc.v8.i1.81] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 11/22/2016] [Accepted: 01/14/2017] [Indexed: 02/05/2023] Open
Abstract
It is worthwhile to measure serum thyroglobulin (TG) level in thyroid cancer before subjecting patients to surgery for two reasons. Firstly, if the level is high, it may give a clue to the local and metastatic tumour burden at presentation; secondly, if the level is normal, it identifies the patients who are unlikely to show rising TG levels in the presence of thyroid cancer. Those who have high serum TG before surgery will show up recurrence as rising serum TG during the postoperative period. Those who do not have high serum TG before surgery will not show up rising serum TG in the presence of recurrent disease. In the latter situation, normal TG level gives only a false reassurance regarding recurrence of disease. Nevertheless, rising serum TG during the postoperative period must be interpreted cautiously because this could be due to the enlargement of non-cancerous residual thyroid tissue inadvertently left behind during surgery.
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van der Horst-Schrivers ANA, Sluiter WJ, Muller Kobold AC, Wolffenbuttel BHR, Plukker JTM, Bisschop PH, de Klerk JM, Al Younis I, Lips P, Smit JW, Brouwers AH, Links TP. Recombinant TSH stimulated remnant ablation therapy in thyroid cancer: the success rate depends on the definition of ablation success--an observational study. PLoS One 2015; 10:e0120184. [PMID: 25793762 PMCID: PMC4367989 DOI: 10.1371/journal.pone.0120184] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Accepted: 02/02/2015] [Indexed: 01/08/2023] Open
Abstract
INTRODUCTION Patients with differentiated thyroid cancer (DTC) are treated with (near)-total thyroidectomy followed by remnant ablation. Optimal radioiodine-131 (131I) uptake is achieved by withholding thyroid hormone (THW), pretreatment with recombinant human Thyrotropin Stimulating Hormone (rhTSH) is an alternative. Six randomized trials have been published comparing THW and rhTSH, however comparison is difficult because an uniform definition of ablation success is lacking. Using a strict definition, we performed an observational study aiming to determine the efficacy of rhTSH as preparation for remnant ablation. PATIENTS AND METHODS Adult DTC patients with, tumor stage T1b to T3, Nx, N0 and N1, M0 were included in a prospective multicenter observational study with a fully sequential design, using a stopping rule. All patients received remnant ablation with 131I using rhTSH. Ablation success was defined as no visible uptake in the original thyroid bed on a rhTSH stimulated 150 MBq 131I whole body scan (WBS) 9 months after remnant ablation, or no visible uptake in the original thyroid bed on a post therapeutic WBS when a second high dose was necessary. RESULTS After interim analysis of the first 8 patients, the failure rate was estimated to be 69% (90% confidence interval (CI) 20-86%) and the inclusion of new patients had to be stopped. Final analysis resulted in an ablation success in 11 out of 17 patients (65%, 95% CI 38-86%). CONCLUSION According to this study, the efficacy of rhTSH in the preparation of 131I ablation therapy is inferior, when using a strict definition of ablation success. The current lack of agreement as to the definition of successful remnant ablation, makes comparison between different ablation strategies difficult. Our results point to the need for an international consensus on the definition of ablation success, not only in routine patient's care but also for scientific reasons. TRIAL REGISTRATION Dutch Trial Registration NTR2395.
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Affiliation(s)
| | - Wim J. Sluiter
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Anneke C. Muller Kobold
- Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Bruce H. R. Wolffenbuttel
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - John T. M. Plukker
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Peter H. Bisschop
- Academic Medical Center, University of Amsterdam, Department of Endocrinology, Amsterdam, the Netherlands
| | - John M. de Klerk
- Meander Medical Center Amersfoort, Department of Nuclear Medicine, Amersfoort, the Netherlands
| | - Imad Al Younis
- Leiden University Medical Center, Department of Nuclear Medicine and Molecular Imaging, Leiden, the Netherlands
| | - Paul Lips
- VU University Medical Center, Department of Internal Medicine/Endocrinology, Amsterdam, the Netherlands
| | - Jan W. Smit
- Radboud University Nijmegen Medical Center, Department of Internal Medicine, Nijmegen, the Netherlands
| | - Adrienne H. Brouwers
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Thera P. Links
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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Agate L, Bianchi F, Giorgetti A, Sbragia P, Bottici V, Brozzi F, Santini P, Molinaro E, Vitti P, Elisei R, Ceccarelli C. Detection of metastases from differentiated thyroid cancer by different imaging techniques (neck ultrasound, computed tomography and [18F]-FDG positron emission tomography) in patients with negative post-therapeutic ¹³¹I whole-body scan and detectable serum thyroglobulin levels. J Endocrinol Invest 2014; 37:967-72. [PMID: 25070043 DOI: 10.1007/s40618-014-0134-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Accepted: 07/09/2014] [Indexed: 10/25/2022]
Abstract
INTRODUCTION DTC patients having detectable Tg and negative post-therapeutic (131)I-WBS have to be investigated by different imaging techniques to detect metastases. PURPOSE Comparison of neck US, CT and [18F]-FDG PET scan. METHODS In 49 DTC patients with biochemical disease, neck was examined by US, CT and [18F]-FDG PET. FNA was performed and Tg was determined by FNA-Tg in selected cases of suspicious lymph nodes. Thorax was examined by CT and PET. Serum Tg was measured on LT4 therapy (basal Tg) and after the stimulation with recombinant human TSH (peak Tg). RESULTS A thyroid remnant was seen by US, CT and PET in eight patients; recurrences were seen by US, CT and PET in six, five and five patients, respectively. Two metastatic nodes were identified by US and CT but not by PET. Lung micronodules were detected by CT in 7/49 (14.3 %) patients and by FDG PET in three of them. Basal Tg ranged from 0.5-1,725 ng/ml while peak Tg ranged from 0.5 to 2,135 ng/ml: the distribution between positive and negative patients was similar. Bone scan was negative in all cases. CONCLUSIONS In DTC patients with detectable Tg and negative I-131 post-therapy WBS, imaging examination revealed remnant or metastases in 43 % of cases. Remnant and recurrences were equally detected by the three techniques; US was better than [18F]-FDG PET for lymph node metastases since this latter method can give false both positive and negative results; chest examination is best made by CT versus FDG PET due to its higher spatial resolution.
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Affiliation(s)
- Laura Agate
- Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Paradisa 2, 56127, Pisa, Italy,
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Pitoia F, Bueno MF, Abelleira E, Salvai ME, Bergoglio L, Luster M, Niepomniszcze H. Undetectable pre-ablation thyroglobulin levels in patients with differentiated thyroid cancer: it is not always what it seems. ACTA ACUST UNITED AC 2013; 57:300-6. [PMID: 23828434 DOI: 10.1590/s0004-27302013000400004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2012] [Accepted: 11/01/2012] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To establish the frequency of U Tg (undetectable pre-ablation thyroglobulin) in TgAb- negative patients and to evaluate the outcome in the follow-up. SUBJECTS AND METHODS We retrospectively reviewed 335 patients' records. Twenty eight patients (9%) had U Tg. Mean follow-up was 42 ± 38 months. All subjects had undergone total thyroidectomy, and lymph nodes were positive in 13 (46%) patients. Tg and TgAb levels were measured 4 weeks after surgery by IMA technology in hypothyroid state. No evidence of disease (NED) status was defined as undetectable (< 1 ng/mL) stimulated Tg and negative Tg-Ab and/or negative WBS, together with normal imaging studies. RESULTS Seventeen patients (61%) were considered with NED. Four patients (14%) had persistent disease (mediastinum, n = 1, lung n = 2, unknown n = 1), and 7 (25%) had detectable TgAb by other method during their follow-up. CONCLUSIONS U Tg levels usually is associated to a complete surgery. However, in a low percentage of patients, this may be related to false negative Tg or TgAb measurement.
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Affiliation(s)
- Fabián Pitoia
- Division of Endocrinology, Hospital de Clinicas, University of Buenos Aires, Buenos Aires, Argentina.
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Jung CH, Goong HJ, Kim BY, Park JM, Kwak JJ, Kim CH, Hong HS, Kang SK, Mok JO. Lung nodule detected by F-18 fluorodeoxyglucose positron emission tomography-computed tomography in patients with papillary thyroid cancer, negative 131I whole body scan, and undetectable serum-stimulated thyroglobulin levels: two case reports. J Med Case Rep 2012; 6:374. [PMID: 23114422 PMCID: PMC3492104 DOI: 10.1186/1752-1947-6-374] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2012] [Accepted: 08/29/2012] [Indexed: 11/19/2022] Open
Abstract
Introduction When a pulmonary nodular lesion is detected by F-18 fluorodeoxyglucose positron emission tomography-computed tomography in a patient with post-surgical papillary thyroid carcinoma with undetectable serum-stimulated thyroglobulin levels and negative 131I whole body scan, diagnosis and management of the nodule may be confusing. Case presentation We describe two post-surgical patients with papillary thyroid carcinoma who showed pulmonary nodular lesions detected by F-18 fluorodeoxyglucose positron emission tomography-computed tomography. In both cases serum-stimulated thyroglobulin levels were undetectable and nodular lesions were not detected by 131I whole body scan. In the first case, a 64-year-old Asian woman showed one focal increased fluorodeoxyglucose uptake lesion in the right lower lobe of one of her lungs. Based on the histologic study, the pulmonary nodular lesion was diagnosed as a solitary pulmonary metastasis from papillary thyroid carcinoma. In the second case, a 59-year-old Asian woman showed a new pulmonary nodule in the right lower lobe. The computed tomography scan of her chest revealed a 9mm nodule in the anterior basal segment and another tiny nodule in the posterior basal segment of the right lower lobe. Six months later, both nodules had increased in size and miliary disseminated nodules were also seen in both lungs. Based on their histology, the pulmonary nodular lesions were considered to be primary lung adenocarcinoma. Conclusions The present cases emphasize that physicians should be cautious and make efforts for an accurate diagnosis of pulmonary nodules detected on F-18 fluorodeoxyglucose positron emission tomography-computed tomography in patients with papillary thyroid carcinoma with no evidence of metastasis such as negative 131I whole body scan and undetectable stimulated serum thyroglobulin levels.
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Affiliation(s)
- Chan-Hee Jung
- Department of Internal Medicine, Division of Endocrinology and Metabolism, Soonchunhyang University School of Medicine, Bucheon, Korea.
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Undetectable Thyroglobulin in Patients With Differentiated Thyroid Carcinoma and Residual Radioiodine Uptake on a Postablation Whole-Body Scan. Clin Nucl Med 2011; 36:109-12. [DOI: 10.1097/rlu.0b013e318203bb84] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Thyroid Follicular Epithelial Cell-Derived Carcinomas: An Overview of the Pathology of Primary and Recurrent Disease. Otolaryngol Clin North Am 2008; 41:1079-94, vii-viii. [DOI: 10.1016/j.otc.2008.08.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Abstract
Differentiated thyroid cancer (DTC) is a rare disease with a generally good prognosis. The initial treatment is total thyroidectomy with ablation of thyroid remnants by iodine-131 (131I). Currently, serum thyroglobulin (Tg) measurement and neck high-resolution ultrasound are the basis of follow-up. The thyroid cells are the only source of Tg in the human body, therefore, the presence of Tg after total thyroidectomy and ablative 131I therapy indicates persistence or recurrence of DTC. The sensitivity of Tg measurements can be optimized by clinical and technical improvements. Clinically, measurements of thyroid-stimulating hormone (TSH)-stimulated Tg after thyroid hormone withdrawal, or exogenous TSH administration in patients with undetectable serum Tg during thyroid hormone-suppression therapy, is recommended for revealing occult disease. Technically, the development of Tg assays with improved functional sensitivity enhances the value of Tg measurements, allowing us to measure Tg without any TSH stimulation during DTC with high negative predictive value. In particular, increasing serum Tg concentrations in highly sensitive assays are early and reliable indicators of recurrent disease. Several imaging methods are available for the localization of recurrences and metastases (i.e., 131I whole-body scan for iodine-positive metastases and fluorodeoxyglucose-PET or PET/CT scans for iodine-negative ones), but their rational use should be dictated by Tg testing results. This will be realized in a limited follow-up protocol, warranting the detection of recurrences of DTC and reducing patient burden and medical costs.
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Affiliation(s)
- Luca Giovanella
- a Department of Nuclear Medicine, PET Centre and Thyroid Unit, Oncology Institute of Southern Switzerland, 6500 Bellinzona, Switzerland.
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Phan HTT, Jager PL, van der Wal JE, Sluiter WJ, Plukker JTM, Dierckx RAJO, Wolffenbuttel BHR, Links TP. The follow-up of patients with differentiated thyroid cancer and undetectable thyroglobulin (Tg) and Tg antibodies during ablation. Eur J Endocrinol 2008; 158:77-83. [PMID: 18166820 DOI: 10.1530/eje-07-0399] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
OBJECTIVE This retrospective study describes the role of serum thyroglobulin (Tg) in relation to tumor characteristics in the prediction of persistent/recurrent disease in patients with differentiated thyroid cancer (DTC) with negative Tg at the time of ablation. DESIGN Between 1989 and 2006, 94 out of 346 (27%) patients with DTC had undetectable Tg at the time of 131I ablation and were included in this evaluation. The group of 94 patients consisted of 15 males and 79 females in the age range of 16-89 years with a median follow-up of 8 years (range 1-17). All medical records and follow-up parameters of the 94 patients were evaluated for the occurrence of persistent/recurrent disease. In patients with persistent/recurrent disease hematoxylin-eosin-stained slides of the primary tumors and/or metastatic lesions were also reviewed for histological features including immunostains for Tg. RESULTS During follow-up, 8 out of 94 (8.5%) patients showed persistent/recurrent disease: in the course of the disease two patients showed Tg positivity, three showed Tg antibody (TgAb) positivity, and the other three showed persistently undetectable Tg and TgAb. Patients who developed Tg and/or TgAb positivity during follow-up had a significantly shorter disease-free survival period when compared with patients with persistently undetectable Tg and TgAb (P<0.006). Histological features were not able to predict the recurrent status. CONCLUSIONS Follow-up of Tg and TgAb in patients with initially negative Tg and TgAb is useful since a number of patients had shown detectable Tg or TgAb during follow-up indicative for persistent/recurrent disease. Tg and TgAb negativity at the time of ablation is not a predictive determinant for future recurrent status.
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Affiliation(s)
- Ha T T Phan
- Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands.
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Hsu CC, Chen YW, Huang YF, Chuang YW. Routine 201Tl scintigraphy in the follow-up of patients with differentiated thyroid carcinoma: diagnostic accuracy and clinical impact. Nucl Med Commun 2007; 28:681-7. [PMID: 17667746 DOI: 10.1097/mnm.0b013e3282742090] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
OBJECTIVE The use of 201Tl scintigraphy as a routine imaging modality in the follow-up of patients with differentiated thyroid carcinoma (DTC) is controversial. The purpose of this retrospective study was to evaluate the diagnostic accuracy and clinical impact of routine 201Tl scintigraphy in the follow-up of patients with DTC. MATERIALS AND METHODS Three hundred and twenty-one patients (261 women, 60 men) with DTC (243 papillary thyroid carcinomas, 78 follicular thyroid carcinomas) were enrolled in this study. Two hundred and seventy-six patients underwent total or near total thyroidectomy (group 1) and 45 patients underwent subtotal thyroidectomy or unilateral lobectomy (group 2). A total of 1523 201Tl scintigraphy examinations were performed between 1987 and 2003. The duration of follow-up ranged from 13 to 204 months. 201Tl scintigraphy was performed 10 and 60 min after intravenous administration of 74 MBq 201Tl chloride. RESULTS In group 1, 55 recurrent lesions were confirmed in 39 patients. In a patient-based analysis, the sensitivity, specificity, positive and negative predictive values, and accuracy of 201Tl scintigraphy for detecting recurrent DTC were 71.8%, 98.3%, 87.5%, 95.5% and 94.6%, respectively. In a lesion-based analysis, the sensitivity, specificity, positive and negative predictive values, and accuracy of 201Tl scintigraphy were 63.6%, 99.7%, 89.7%, 98.5% and 98.3%, respectively. Of the 35 thallium-positive recurrent lesions, 21 (60%) were removed by surgery and seven (20%) were treated with external-beam radiation therapy. All the thallium-negative recurrent lesions were treated with 131I therapy. The difference between the management of thallium-positive and thallium-negative recurrences was statistically significant (P<0.001). In group 2, 10 recurrent lesions were confirmed in seven patients. In a patient-based analysis, the sensitivity, specificity, positive and negative predictive values, and accuracy of 201Tl scintigraphy for detecting recurrent DTC were 85.7%, 94.7%, 75%, 97.3% and 93.3%, respectively. In a lesion-based analysis, the sensitivity, specificity, positive and negative predictive values, and accuracy of 201Tl scintigraphy was 80%, 97.5%, 80%, 97.5% and 95.6%, respectively. All of the seven patients were treated with completion of total thyroidectomy and subsequent 131I ablation therapy. CONCLUSIONS 201Tl scintigraphy was not a highly sensitive imaging modality in routine follow-up of patients with DTC after total thyroidectomy. However, it had a clinical impact on the choice of optimal therapeutic approaches. In the follow-up of patients who underwent partial thyroidectomy, 201Tl scintigraphy was useful in the detection of recurrent DTC.
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Affiliation(s)
- Chien-Chin Hsu
- Department of Nuclear Medicine, Pingtung Christian Hospital, Taiwan
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16
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Giovanella L, Ceriani L, Ghelfo A, Maffioli M, Keller F. Preoperative undetectable serum thyroglobulin in differentiated thyroid carcinoma: incidence, causes and management strategy. Clin Endocrinol (Oxf) 2007; 67:547-51. [PMID: 17561976 DOI: 10.1111/j.1365-2265.2007.02922.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND In recent years serum thyroglobulin (Tg) measurement during thyroxine (T4) treatment and/or after stimulation by endogenous TSH or recombinant human TSH (rhTSH) has eclipsed other diagnostic procedures in managing patients with differentiated thyroid cancer (DTC). However, preoperative undetectable Tg was reported in up to 12% of patients affected by DTC and recurrences of DTC with no increase in serum Tg have also been described. Clearly, a negative Tg measurement may falsely reassure both the patient and the clinician in these cases. AIM We retrospectively evaluated the incidence of undetectable or reduced preoperative serum Tg in a group of 436 patients affected by DTC. Additionally, we evaluated the role of Tg retesting by two different immunoassays in patients with low Tg at first measurement. METHODS We retrospectively selected 17 patients with undetectable (i.e. less than functional sensitivity of assay method) or reduced Tg (i.e. between functional sensitivity and minimum normal value) among 436 patients with histologically proved DTC. The remaining 419 patients were used as control cases. Frozen sera from all patients were retested by two different Tg immunoassays. RESULTS Globally, 17 out of 436 (3.8%) patients showed undetectable (n = 5, 1.1%) or reduced (n = 12, 2.7%) preoperative Tg. The Tg level was above the minimum normal value in 3 and 4 out of 5, and 8 and 9 out of 12 of these patients, respectively, when two different immunoassays were employed. On the other hand, undetectable or reduced Tg levels were found in 3.0%-5.1% of control cases when different immunoassays were used. CONCLUSIONS Regardless of the method employed, 3.0-5.1% of patients with DTC showed undetectable or reduced preoperative Tg. This fact must be recognized, as Tg cannot be used as a benchmark for DTC follow-up in these cases. However, Tg retesting with different immunoassays seems to be useful in ruling out these pitfalls in a large majority of patients, and also indicates the most effective assay to be employed in these cases.
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MESH Headings
- Adenocarcinoma, Follicular/blood
- Adenocarcinoma, Follicular/radiotherapy
- Adenocarcinoma, Follicular/surgery
- Adenoma, Oxyphilic/blood
- Adenoma, Oxyphilic/radiotherapy
- Adenoma, Oxyphilic/surgery
- Adult
- Aged
- Biomarkers/blood
- Carcinoma, Papillary/blood
- Carcinoma, Papillary/radiotherapy
- Carcinoma, Papillary/surgery
- Case-Control Studies
- Female
- Follow-Up Studies
- Humans
- Immunoradiometric Assay/methods
- Incidence
- Iodine Radioisotopes/therapeutic use
- Male
- Middle Aged
- Neoplasm Recurrence, Local/blood
- Neoplasm Recurrence, Local/radiotherapy
- Radiopharmaceuticals/therapeutic use
- Retrospective Studies
- Sensitivity and Specificity
- Thyroglobulin/blood
- Thyroid Neoplasms/blood
- Thyroid Neoplasms/radiotherapy
- Thyroid Neoplasms/surgery
- Thyroidectomy
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Affiliation(s)
- Luca Giovanella
- Nuclear Medicine and Thyroid Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
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17
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Schlumberger M, Lacroix L, Russo D, Filetti S, Bidart JM. Defects in iodide metabolism in thyroid cancer and implications for the follow-up and treatment of patients. ACTA ACUST UNITED AC 2007; 3:260-9. [PMID: 17315034 DOI: 10.1038/ncpendmet0449] [Citation(s) in RCA: 92] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2006] [Accepted: 10/20/2006] [Indexed: 12/13/2022]
Abstract
The two major steps of iodine metabolism--uptake and organification--are altered in thyroid cancer tissues. Organification defects result in a rapid discharge of radioiodine from thyroid cells, a short effective half-life of iodine, and a low rate of thyroid hormone synthesis. These defects are mainly due to decreased expression of functional genes encoding the sodium-iodide symporter and thyroid peroxidase and could result in a low radiation dose to thyroid cancer cells. TSH stimulation that is achieved with injections of recombinant human TSH, or long-term withdrawal of thyroid hormone treatment increases iodine-131 uptake in two-thirds of patients with metastatic disease and increases thyroglobulin production in all patients with metastases, even in the absence of detectable uptake. Serum thyroglobulin determination obtained following TSH stimulation and neck ultrasonography is the most sensitive combination for the detection of small tumor foci. Radioiodine treatment is effective when a high radiation dose can be delivered (in patients with high uptake and retention of radioiodine) and when tumor foci are sensitive to the effects of radiation therapy (younger patients, with a well-differentiated tumor and/or with small metastases). The other patients rarely respond to radioiodine treatment, and when progression occurs, other treatment modalities should be considered. Novel strategies are currently being explored to restore iodine uptake in cancer cells that are unable to concentrate radioiodine.
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18
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Huang SH, Wang PW, Huang YE, Chou FF, Liu RT, Tung SC, Chen JF, Kuo MC, Hsieh JR, Hsieh HH. Sequential follow-up of serum thyroglobulin and whole body scan in thyroid cancer patients without initial metastasis. Thyroid 2006; 16:1273-8. [PMID: 17199438 DOI: 10.1089/thy.2006.16.1273] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
OBJECTIVE To investigate the usefulness of whole body scan (WBS) and serum thyroglobulin (Tg) measurement after thyroxine withdrawal during sequential follow-ups in patients with differentiated thyroid cancer (DTC). DESIGN Two hundred and sixty-five consecutive DTC patients were enrolled. They were previously treated with near-total thyroidectomy and I-131 remnant ablation, without initial metastases or Tg antibodies. All had the first follow-up WBS and serum Tg measurement 6-12 months after initial treatment, and 165 patients received the second follow-up without further therapy. Positive/negative predictive values (PPV/NPV) were calculated by the outcome of patients being followed up for more than 8 years (mean+/-SD: 133+/-26 months). RESULTS Serum Tg levels while the patients were off thyroxine therapy decreased spontaneously in 39.3% of the cases without further therapy. The NPV of the first follow-up serum Tg level was excellent: <2 microg/L and <0.5 microg/L were 95.1% and 98.2%, respectively. However, the PPV of the first follow-up serum Tg level was low: >10 microg/L and 2-10 microg/L were 40% and 9.6%, respectively. The trend of Tg levels was more informative; the PPV was 62.5% in cases with an increase of serum Tg of >10 microg/L and 16.6% with an increase of <5 microg/L. However, decreasing Tg levels may associate with rapid deterioration of disease, in which cases decrease of Tg indicated dedifferentiation of the tumor. The diagnostic WBS showed the same picture in 91.5% of the patients. Only one patient (0.6%) turned from negative study to positive during the follow-up. In the meanwhile his serum Tg levels increased from 0.56 to 13.6 microg/L. CONCLUSION It is most informative when both the trend and the levels of Tg during sequential follow-up are considered. The diagnostic WBS may be performed for selected patients with indication based on Tg levels to localize the disease.
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Affiliation(s)
- Shu-Hua Huang
- Department of Nuclear Medicine, Chang Gung Memorial Hospital-Ksohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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19
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Choi MY, Chung JK, Lee HY, So Y, Park DJ, Jeong JM, Lee DS, Lee MC, Cho BY. The clinical impact of18F-FDG PET in papillary thyroid carcinoma with a negative131I whole body scan: A single-center study of 108 patients. Ann Nucl Med 2006; 20:547-52. [PMID: 17134022 DOI: 10.1007/bf03026819] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
OBJECTIVE To assess whether FDG PET could localize the recurrent or metastatic lesions in papillary thyroid cancer patients with negative radioiodine scan. METHODS Whole body PET was performed after injecting 370-555 MBq of 18F-FDG in 108 patients, who were suspected of having recurrence or metastasis and whose 131I whole body scans were negative. Recurrence or metastasis occurred in 63 patients by pathology or clinical assessment, whereas 45 patients remained in remission. RESULTS FDG PET revealed recurrence or metastases in 59 patients (sensitivity 93.7%), whereas thyroglobulin (Tg) levels were elevated in 41 (sensitivity 65.1%). In 35 of 45 patients in remission, FDG PET was negative (specificity 77.8%). When patients positive for antithyroglobulin antibody were excluded, the sensitivity and specificity of serum Tg became 84.8% and 46.9%, respectively. Compared to Tg measurement, FDG PET detected more metastatic lesions in cervical lymph nodes. Of 40 patients with a negative radioiodine scan showing diffuse hepatic uptake, metastases occurred in 23 patients and remission in 17. FDG PET showed 100% sensitivity and 76.5% specificity in the detection of recurrence in these 40 patients. CONCLUSION FDG PET is useful for localizing recurrent or metastatic lesions in 131I scan-negative thyroid cancer patients. In particular, it is superior to serum Tg measurement for identifying metastases to cervical lymph nodes. We recommend its use in cases of negative radioiodine scan with diffuse hepatic uptake.
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Affiliation(s)
- Mi-Yeon Choi
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea
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20
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Lind P, Kohlfürst S. Respective Roles of Thyroglobulin, Radioiodine Imaging, and Positron Emission Tomography in the Assessment of Thyroid Cancer. Semin Nucl Med 2006; 36:194-205. [PMID: 16762610 DOI: 10.1053/j.semnuclmed.2006.03.002] [Citation(s) in RCA: 74] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Depending on the iodine supply of an area, the incidence of thyroid cancer ranges between 4 and 12/100,000 per year. To detect thyroid cancer in an early stage, the assessment of thyroid nodules includes ultrasonography, ultrasonography-guided fine-needle aspiration biopsy, and conventional scintigraphic methods using (99m)Tc-pertechnetate, (99m)Tc-sestamibi or -tetrofosmin, and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in selected cases. After treatment of thyroid cancer, a consequent follow-up is necessary over a period of several years. For following up low-risk patients, recombinant thyroid-stimulating hormone-stimulated thyroglobulin and ultrasonography is sufficient in most cases. After total thyroidectomy and radioiodine ablation therapy, thyroid-stimulating hormone-stimulated thyroglobulin should be below the detection limit (eg, <0.5 ng/mL, R: 70-130). An increase of thyroglobulin over time is suspicious for recurrent or metastatic disease. Especially in high-risk patients, aside from the use of ultrasonography for the detection of local recurrence and cervial lymph node metastases, nuclear medicine methods such as radioiodine imaging and FDG-PET are the methods of choice for localizing metastatic disease. Radioiodine imaging detects well-differentiated recurrences and metastases with a high specificity but only moderate sensitivity. The sensitivity of radioiodine imaging depends on the activity administered. Therefore a low activity diagnostic (131)I whole-body scan (74-185 MBq) has a lower detection rate than a high activity post-therapy scan (3700-7400 MBq). In patients with low or dedifferentiated thyroid cancer and after several courses of radioiodine therapy caused by metastatic disease, iodine negative metastases may develop. In these cases, despite clearly elevated levels of thyroglobulin, radioiodine imaging is negative or demonstrates only faint iodine uptake. The method of choice to image these iodine negative metastases is FDG-PET. In recent years the combination of PET and computed tomography has been introduced. The fusion of the metabolic and morphologic information was able to increase the diagnostic accuracy, reduces pitfalls and changes therapeutic strategies in a reasonable number of patients.
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MESH Headings
- Adenocarcinoma, Follicular/blood
- Adenocarcinoma, Follicular/diagnostic imaging
- Adenocarcinoma, Follicular/secondary
- Biomarkers, Tumor/blood
- Biopsy, Fine-Needle
- Carcinoma, Papillary/blood
- Carcinoma, Papillary/diagnostic imaging
- Carcinoma, Papillary/secondary
- Fluorodeoxyglucose F18
- Follow-Up Studies
- Humans
- Iodine Radioisotopes
- Liver Neoplasms/diagnostic imaging
- Liver Neoplasms/secondary
- Lung Neoplasms/diagnostic imaging
- Lung Neoplasms/secondary
- Lymphatic Metastasis/diagnostic imaging
- Neoplasm Recurrence, Local/diagnostic imaging
- Positron-Emission Tomography
- Preoperative Care
- Radiometry/methods
- Radiopharmaceuticals
- Sensitivity and Specificity
- Thyroglobulin/blood
- Thyroid Neoplasms/blood
- Thyroid Neoplasms/diagnostic imaging
- Thyroid Nodule/diagnostic imaging
- Thyroid Nodule/pathology
- Thyrotropin
- Tomography, Emission-Computed, Single-Photon
- Tomography, X-Ray Computed/methods
- Ultrasonography
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Affiliation(s)
- Peter Lind
- Department of Nuclear Medicine and Endocrinology, PET/CT Center Klagenfurt, Austria.
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21
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Alzahrani AS, Mohamed GE, Al Rifai A, Al-Sugair A, Abdel Salam SA, Sulaiman OM, Demirkaya O. Role Of [18F]Fluorodeoxyglucose Positron Emission Tomography In Follow-Up Of Differentiated Thyroid Cancer. Endocr Pract 2006; 12:152-8. [PMID: 16690462 DOI: 10.4158/ep.12.2.152] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE To assess the diagnostic utility of [(18)F]flu-orodeoxyglucose positron emission tomography (FDG PET) in the follow-up of patients with differentiated thyroid cancer (DTC). METHODS In this study, we used strict definitions of presence and absence of the disease and performed all FDG PET scans while the patients were not taking levothyroxine (LT4). We report the results of conventional FDG PET scans obtained during the follow-up of 50 nonselected patients with DTC (34 female and 16 male patients; median age, 40.5 years; range, 18 to 68). All FDG PET scans and measurement of thyroglobulin (Tg) levels were performed while the patients were not taking LT4 (thyrotropin>or=25 microIU/mL). Tg antibodies were negative in all patients. The initial surgical procedure was total thyroidectomy in all cases, and 26 patients underwent additional operations (2 to 4 procedures). Radioactive iodine (131I) therapy was given to 48 patients (median dose, 5,550 MBq). In 42 patients, FDG PET was used for evaluation of Tg-positive (Tg>2 ng/mL in the absence of LT4 therapy), scan-negative disease. In 8 patients, Tg was <or=2 ng/mL but other findings suggested the presence of the disease (detectable Tg in 7 cases and abnormal ultrasound findings in 3). Disease was considered present if confirmed by fine-needle aspiration, histopathologic examination of subsequent surgical specimens, or persistent elevation of Tg levels (>2 ng/mL without LT4 therapy) for >1 year. Disease was considered absent if Tg was <or=2 ng/mL and at least all the following imaging studies were negative: diagnostic radioiodine whole-body scan, chest radiography or spiral computed tomography of the chest, and high-resolution neck ultrasonography. If all these criteria were present, a positive FDG PET scan was considered a false-positive study. RESULTS FDG PET scans were positive in 27 patients (54%) and negative in 23 (46%). FDG PET results were true-positive in 26 cases, false-positive in 1, true-negative in 7, and false-negative in 16. The sensitivity, specificity, and positive and negative predictive values were 61.9%, 87.5%, 96.3%, and 30.4%, respectively. CONCLUSION FDG PET scanning is moderately sensitive and specific for detection of persistent or recurrent DTC.
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Affiliation(s)
- Ali S Alzahrani
- Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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22
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Rezk S, Khan A. Role of Immunohistochemistry in the Diagnosis and Progression of Follicular Epithelium-Derived Thyroid Carcinoma. Appl Immunohistochem Mol Morphol 2005; 13:256-64. [PMID: 16082252 DOI: 10.1097/01.pai.0000142823.56602.fe] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Thyroid carcinoma derived from the thyroid hormone-producing follicular epithelium is the most common thyroid malignancy. While the morphologic diagnosis of conventional papillary thyroid carcinoma is simple, thyroid tumors with a follicular pattern are sometimes a diagnostic challenge. It is in the latter group of thyroid neoplasms that ancillary diagnostic tests such as immunohistochemistry may be of great help. Furthermore, while most differentiated thyroid carcinomas have an excellent prognosis, a subset of these tumors may progress to a poorly or undifferentiated phenotype indicating an aggressive biologic behavior that may lead to systemic spread and death. Application of immunohistochemistry to identify a subset of thyroid carcinoma that may progress to a biologically aggressive phenotype may help in the management of patients with thyroid carcinoma. This review discusses the role of immunohistochemistry in the diagnosis and progression of thyroid carcinoma is discussed.
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Affiliation(s)
- Sherif Rezk
- Department of Pathology, University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, Massachusetts 01655, USA
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23
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Salvatori M, Perotti G, Rufini V, Maussier ML, Dottorini M. Are there disadvantages in administering 131I ablation therapy in patients with differentiated thyroid carcinoma without a preablative diagnostic 131I whole-body scan? Clin Endocrinol (Oxf) 2004; 61:704-10. [PMID: 15579184 DOI: 10.1111/j.1365-2265.2004.02153.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To evaluate the risk of performing inappropriate (131)I ablative therapies for thyroid carcinoma in patients lacking thyroid remnants or metastases, using a strategy of treatment without a preliminary iodine-131 diagnostic whole-body scan (DxWBS). DESIGN Retrospective evaluation of post-therapy whole-body scans to assess the prevalence of thyroid remnants or metastases after total thyroidectomy. Comparison of (131)I uptake test and thyroglobulin (Tg) off levothyroxine (L-T4) performed before therapy with post-therapy scans, in order to evaluate the ability to predict inappropriate treatments. PATIENTS A group of 875 consecutive patients with previous total or near-total thyroidectomy for differentiated thyroid carcinoma underwent (131)I ablative therapy without a preliminary (131)I-DxWBS. All patients were clinically free of distant metastases and macroscopic residual tumour. MEASUREMENTS Whole-body scans were performed 2-5 days after the treatment as gold standard for thyroid remnants and metastases; 24-h (131)I quantitative neck uptake test and Tg off L-T4 were performed before (131)I therapy. RESULTS The majority of patients (94%) were found to have thyroid remnants or metastases at post-therapy scans, in most cases (91.2%) with detectable Tg off L-T4 and positive 24-h neck uptake. 14 patients (1.6%) with tiny lymph-node metastases positive at post-therapy scans showed undetectable Tg off L-T4. In 30 patients (3.6%) faint positive post-therapy images for thyroid remnants have been classified as false-positive results on the basis of both negative 24-h neck uptake and undetectable Tg off L-T4. CONCLUSIONS This study confirms that most patients have residual thyroid tissue after total thyroidectomy and that it seems reasonable to omit routine diagnostic whole-body scans before (131)I treatment with clinical, managerial and economic advantages.
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Affiliation(s)
- Massimo Salvatori
- Institute of Nuclear Medicine, Catholic University of the Sacred Heart, Rome, Italy.
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24
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Ceccarelli C, Bianchi F, Trippi D, Brozzi F, Di Martino F, Santini P, Elisei R, Pinchera A. Location of functioning metastases from differentiated thyroid carcinoma by simultaneous double isotope acquisition of I-131 whole body scan and bone scan. J Endocrinol Invest 2004; 27:866-9. [PMID: 15648552 DOI: 10.1007/bf03346282] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
In a young patient with differentiated thyroid carcinoma (DTC), previously submitted to total thyroidectomy and I-131 therapy for ablation of thyroid remnant, a follow-up 1-131 diagnostic whole body scan (WBS) demonstrated four small abnormal I-131 uptake areas. Two of these were projected over the thoracic region and corresponded to lung nodules, as later demonstrated by lung computerized tomography (CT)-scan. The remaining two areas were found in the lumbar-pelvic region, but their precise location could not be determined. Standard bone Rx examination and bone scan were negative. After I-131 therapy, we simultaneously acquired a I-131 WBS and a Tc-99m oxidronate bone scan by setting a dual window on the gamma camera. Comparing the I-131 and bone images we were able to identify the 4th lumbar vertebra and right ilium as the bone segments to be studied by a radiological approach. Eventually, the thin slice CT-scan demonstrated the presence of two small osteolytic lesions in these areas. In conclusion, the simultaneous acquisition of images both from I-131 and a bone-seeking agent may be useful to locate functioning bone metastases from DTC.
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Affiliation(s)
- C Ceccarelli
- Department of Endocrinology, University of Pisa, Pisa, Italy.
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25
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Hamy A, Mirallié E, Bennouna J, Resche I, Drefty C, Johnstone M, Visset J. Thyroglobulin monitoring after treatment of well-differentiated thyroid cancer. Eur J Surg Oncol 2004; 30:681-5. [PMID: 15256244 DOI: 10.1016/j.ejso.2004.03.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/20/2004] [Indexed: 10/26/2022] Open
Abstract
AIMS The prognosis for well-differentiated thyroid carcinomas is favourable after treatment, but the rate of recurrence is around 20%. Cervical ultrasonography, radio-iodine scans, and monitoring of serum thyroglobulin (Tg) levels allow these recurrences to be diagnosed. The management of patients with isolated elevated Tg levels is controversial in the presence of negative radio-iodine scans. METHODS The records of 57 patients diagnosed with recurrence of well-differentiated thyroid cancer were reviewed. Serum Tg was not evaluated in 31 of these patients (group 1) and measured in the other 26 cases (group 2). RESULTS Forty-three recurrence sites were found; four deposits in the thyroid bed and 39 cervical metastatic nodes, with an average of five nodes per patient. The radio-iodine scan was accurate in detecting 10/24 of cases, radiology in 9/17, and elevated Tg levels in 20/25. Thirteen patients with recurrences diagnosed on the basis of Tg levels had negative radio-iodine scans. After surgery, Tg levels were normal in 10 patients from group 1 and 16 patients from group 2 (p=0.0078). CONCLUSIONS Elevated Tg levels are indicative of disease progression or recurrence in patients who have previously been operated on for well-differentiated thyroid cancer. Even when the radiological study or radio-iodine scan is normal, surgical re-exploration of the neck, with total thyroidectomy and lymphadenectomy, is advisable.
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MESH Headings
- Adenocarcinoma, Follicular/blood
- Adenocarcinoma, Follicular/diagnosis
- Adenocarcinoma, Follicular/surgery
- Adenocarcinoma, Papillary/blood
- Adenocarcinoma, Papillary/diagnosis
- Adenocarcinoma, Papillary/surgery
- Adolescent
- Adult
- Aged
- Biomarkers, Tumor/blood
- Disease Progression
- Female
- Humans
- Lymph Node Excision/methods
- Male
- Middle Aged
- Neck
- Neoplasm Recurrence, Local/blood
- Neoplasm Recurrence, Local/diagnosis
- Neoplasm Recurrence, Local/surgery
- Retrospective Studies
- Thyroglobulin/blood
- Thyroid Neoplasms/blood
- Thyroid Neoplasms/diagnosis
- Thyroid Neoplasms/surgery
- Thyroidectomy/methods
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Affiliation(s)
- A Hamy
- Department of Surgery, University Hospital, 49933 Angers Cedex, France.
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26
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Abstract
Thyroglobulin measurements in tissue and serum play an integral role in the evaluation of patients who have thyroid cancer. Immunohistochemical detection of thyroglobulin in surgical specimens is useful in the differential diagnosis of tumors of unknown origin; however, the most important application of thyroglobulin measurement in clinical practice is in the postsurgical management of differentiated thyroid cancer. Serum thyroglobulin is a highly specific and sensitive tumor marker for detecting persistent or recurrent thyroid cancer and for monitoring clinical status. The reappearance of circulating thyroglobulin after total thyroid ablation is pathognomonic for the presence of tumor. The measurement of thyroglobulin in serum is challenging, however, and several analytical problems limit assay performance. Thyroglobulin autoantibody interference is a particularly significant concern that requires all thyroglobulin samples to be screened for their presence. No immunoassay is totally free from interference by thyroglobulin autoantibodies. Measurement of thyroglobulin mRNA to detect circulating tumor cells may help to overcome some of the limitations of current protein-detection methods; serum thyroglobulin will continue to remain the "gold standard." The complex functional features of thyroid carcinomas make sole reliance upon any one diagnostic technique, including thyroglobulin assessments, potentially misleading. Thyroglobulin measurements are a critical component of a multifaceted diagnostic approach to this disease.
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Affiliation(s)
- Ronald J Whitley
- Department of Pathology and Laboratory Medicine, 800 Rose Street, University of Kentucky, Lexington, KY 40536-02963, USA.
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27
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Golger A, Fridman TR, Eski S, Witterick IJ, Freeman JL, Walfish PG. Three-week thyroxine withdrawal thyroglobulin stimulation screening test to detect low-risk residual/recurrent well-differentiated thyroid carcinoma. J Endocrinol Invest 2003; 26:1023-31. [PMID: 14759077 DOI: 10.1007/bf03348202] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Measurement of serum TSH-stimulated thyroglobulin (Tg) is recognized as a sensitive method for detecting residual/recurrent well-differentiated thyroid carcinoma (WDTC) in patients previously treated by surgery and radioactive iodine (RAI) ablation therapy. WDTC patients who have an undetectable serum Tg on thyroid hormone therapy (THT) in the absence of Tg-antibody interference are considered to be at low risk for residual/recurrent disease. Traditional management has been to withdraw T4 for 4-6 weeks or T3 for 2 weeks to stimulate endogenous TSH. However, this prolonged THT withdrawal induces hypothyroidism and its concomitant morbidity. In the present study, we assess the efficacy of shortening the time of T4 withdrawal to only 3 weeks for detecting residual/recurrent WDTC as a sufficient serum TSH stimulus for obtaining a positive serum Tg result without a routine diagnostic whole body scan (WBS). Additionally, we have evaluated the impact of such a T4 withdrawal interval on quality of life and loss of employment time. A total of 181 patients with WDTC selected for study had previously been treated with a bilateral surgical thyroidectomy followed by RAI ablation therapy (average post-surgery to follow-up interval of 10.8 yr). All of the cohort had an undetectable (< 1 microg/l) serum Tg on THT without Tg-antibody interference. Serum TSH and Tg were measured before and after cessation of T4 therapy for 3 weeks. A serum Tg > or = 2 microg/l was considered positive for residual/recurrent disease. A quality of life questionnaire [Short-Form 36 (SF-36)] was administered before withdrawal, at peak TSH and after resumption of therapy. From the completed SF-36 questionnaires, the overall degree of functional impairment was not severe and did not result in loss of employment time. Moreover, this protocol identified three possible responses to the 3-week T4 withdrawal interval as follows: a) serum Tg undetectable with TSH > or = 25 mIU/l (approximately 75% of total cohort); b) serum Tg > or = 2 microg/l (approximately 10% of total cohort) which will require further investigation and treatment for residual/recurrent disease; c) undetectable serum Tg with inadequate TSH rise (approximately 15% of total cohort), which will require TSH stimulation by either longer T4 withdrawal or recombinant human TSH to exclude residual disease. We conclude that a stimulated serum Tg test performed 3 weeks after T4 withdrawal is a simple and cost-effective first-line screening test with minimal morbidity which is sufficient to evaluate low-risk WDTC patients for recurrent/residual carcinoma.
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Affiliation(s)
- A Golger
- Department of Otolaryngology, Mount Sinai Hospital, University of Toronto Medical School, Toronto, Ontario, Canada
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Stojadinovic A, Shoup M, Nissan A, Ghossein RA, Shah JP, Brennan MF, Shaha AR. Recurrent differentiated thyroid carcinoma: biological implications of age, method of detection, and site and extent of recurrence. Ann Surg Oncol 2002; 9:789-98. [PMID: 12374663 DOI: 10.1007/bf02574502] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND We identified factors predictive of outcome for recurrent differentiated thyroid carcinoma (DTC). METHODS Fifty-seven patients with local (LR), regional (RRec), and/or distant recurrence (DR) of 431 recurrent DTCs were studied. Disease-specific survival (DSS) rate was estimated with the Kaplan-Meier method. Univariate and multivariate comparisons were conducted by log-rank and Cox regression analysis. RESULTS The median follow-up was 13 years. Distribution of the first relapse was LR only (35%), LR and RRec (23%), LR and DR (30%), and LR, RRec, and DR (12%). Factors predictive of resectability were a long (>or=5-year) disease-free interval (DFI) and subclinical and thyroid remnant recurrence. Only 26% of symptomatic and 45% of thyroid bed LR, and 43% with DFI <5 years, could be resected completely. No isolated thyroid remnant and 75% of thyroid bed LR resulted in tumor-related mortality. Age <45 years, subclinical recurrence, isolated LR, and the ability to render the patient disease free independently predicted DSS. Fifteen-year DSS for LR only; LR and RRec; LR and DR; and LR, RRec, and DR were 49%, 28%, 15%, and 0%, respectively. CONCLUSIONS Isolated thyroid remnant recurrence defines a benign phenotype. Age, method of detection, site and extent of recurrence, and the ability to render the patient disease free predict outcome for recurrent DTC. Multimodality long-term follow-up is warranted to detect recurrence at a subclinical potentially curative stage.
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Affiliation(s)
- Alexander Stojadinovic
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York , USA.
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29
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Visset J, Hamy A, Mirallie E, Paineau J. [Locoregional recurrence of differentiated thyroid cancers: diagnosis-treatment]. ANNALES DE CHIRURGIE 2002; 127:35-9. [PMID: 11833304 DOI: 10.1016/s0003-3944(01)00672-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
AIM OF THE STUDY To evaluate the improvement of the diagnosis and the treatment of local recurrences (LR) in patients with differentiated thyroid carcinoma. MATERIAL AND METHOD Among a total of 57 patients, two groups were compared: group I: 31 patients operated on from 1974 to 1990; group II: 26 patients operated on from 1991 to 2000. In the group I, the diagnosis of the cervical recurrence was supported by imaging study (ultrasonography, tomodensitometry), in the group II by radioiodinescan and serum thyroglobuline (Tg) measurement. The main difference was the consideration of Tg measurement to detect the recurrence in the group II. A high level of Tg was the only abnormality for 9 patients of the group II. RESULTS A nodal recurrence was respectively present in the group I and II in 88.8% and 92% of the cases. Re-operation consisting in thyroid totalisation and bilateral lymphadenectomy was respectively performed in 71% and 100% of the cases. Surgery associated with iodine 131 therapy was respectively the treatment for 45.1% and 88.4% of the cases. After a median follow up of 66.2 months; results of the group I were as follow: normal or undetectable Tg: 10 (33.3%), second or more cervical recurrences: 7, distant metastases: 11, death in relation to thyroid cancer: 11. After a median follow up of 36.3 months, results of the group II were as follow: normal or undetectable Tg: 17 (65.4%), second or more cervical recurrences: 6, distant metastasis: 5, death in relation to thyroid cancer: 1. The best results concerned patients with an isolated elevated Tg without anatomical location of the first LR. CONCLUSION LR diagnosis is difficult and needs imaging study, radioiodine-scan and serum Tg determination together. Re-operation associated with radioiodine-therapy is the treatment of choice. Elevated serum Tg is suffisant to indicate re-operation even if no anatomical substrate is found. Iodine-radiotherapy alone is generally unable to obtain undetectable serum Tg.
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Affiliation(s)
- J Visset
- Clinique chirurgicale I, hôpital Guillaume et René Laënnec, 44093 Nantes, France
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30
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Hammersley PA, Al-Saadi A, Chittenden S, Flux GD, McCready VR, Harmer CL. Value of protein-bound radioactive iodine measurements in the management of differentiated thyroid cancer treated with (131)I. Br J Radiol 2001; 74:429-33. [PMID: 11388991 DOI: 10.1259/bjr.74.881.740429] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Measurement of the protein-bound radioactive iodine level (PBI(131)) in the plasma of patients following (131)I-iodide administration for thyroid cancer has been re-examined in a retrospective study of 171 patient episodes. It is shown that whereas the previously used threshold value for the measurement at 6 days does not correlate well with the 3-day whole body scan, there is good agreement between the scan and the temporal changes in PBI(131) from 1-6 days: an increasing PBI(131) correlates with a positive scan, and a decreasing PBI(131) with a negative scan. The area under the curve (AUC) for the PBI(131)-time curve is related to the absorbed dose for the tumour. For a small group of 11 patients, dosimetry estimates were made from serial scans, quantified with phantoms; these absorbed doses correlated with the AUC and the 6-day PBI(131). Therefore, it is suggested that these parameters may be useful in predicting absorbed radiation dose in these patients.
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Affiliation(s)
- P A Hammersley
- Department of Nuclear Medicine, Royal Marsden Hospital NHS Trust, Downs Road, Sutton, Surrey SM2 5PT, UK
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31
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Regional Thyroid Cancer Group. Northern Cancer Network Guidelines for Management of Thyroid Cancer. Clin Oncol (R Coll Radiol) 2000. [DOI: 10.1053/clon.2000.9197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Oertli D, Harder F. Surgical approach to thyroid nodules and cancer. BAILLIERE'S BEST PRACTICE & RESEARCH. CLINICAL ENDOCRINOLOGY & METABOLISM 2000; 14:651-66. [PMID: 11289740 DOI: 10.1053/beem.2000.0108] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Fine needle aspiration cytology is the mainstay of the diagnostic work-up of solitary thyroid nodules. Together with the patient's history and the clinical findings, cytology determines the indication for surgery. The minimal intervention for a suspicious nodule consists of thyroid lobectomy. If a diagnosis of malignancy is established, then we recommend total thyroidectomy for all follicular lesions that are larger than 1.5 cm and for high-risk papillary tumours. Near-total thyroidectomy may be appropriate for low-risk patients with papillary carcinoma in whom it is not intended to use radioactive iodine ablation. Whereas ipsilateral lymphadenectomy of the central (primary) compartment should routinely be performed, modified radical neck dissection is only indicated in evident nodal disease of the lateral (secondary) compartment(s). Patients with incidentally discovered differentiated thyroid carcinomas generally do not require complete thyroidectomy unless the tumours are larger than 1.5 cm in diameter or nodal involvement is present. A detailed description of the surgical technique for thyroidectomy and lymphadenectomy is given and an overview of surgical complications is provided.
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Affiliation(s)
- D Oertli
- Department of Surgery, University Hospital of Basel, Spitalstrasse 21, CH-4031 Basel, Switzerland
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