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S C Clement Department of Pediatrics, Emma Children’s Hospital, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital/ University Medical Center Utrecht, Utrecht, The Netherlands

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W E Visser Academic Center For Thyroid Disease, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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C A Lebbink Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital/ University Medical Center Utrecht, Utrecht, The Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

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D Albano Department of Nuclear Medicine, University of Brescia and Spedali Civili of Brescia, Brescia, Italy

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H L Claahsen-van der Grinten Department of Pediatrics, Radboud University Medical Center, Amalia Children's Hospital, Nijmegen, The Netherlands

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A Czarniecka The Oncologic and Reconstructive Surgery Clinic, M. Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland

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R P Dias Department of Endocrinology and Diabetes, Birmingham Children’s Hospital, Birmingham Women’s, and Children’s NHS Foundation Trust, Birmingham, UK
Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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M P Dierselhuis Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

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I Dzivite-Krisane Department of Pediatric Endocrinology, Children's Clinical University Hospital, Riga, Latvia

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R Elisei Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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A Garcia-Burillo Nuclear Medicine Department, Vall d'Hebron University Hospital, Barcelona, Spain

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L Izatt Department of Clinical Genetics, Guy's and St Thomas’ NHS Foundation Trust, London, UK

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C Kanaka-Gantenbein Division of Endocrinology, Diabetes, and Metabolism, First Department of Pediatrics National and Kapodistrian University of Athens Medical School, Aghia Sophia Children's Hospital, Athens, Greece

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H Krude Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin, Berlin, Germany

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L Lamartina Department of Endocrine Oncology, Gustave Roussy, Villejuif, France

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K Lorenz Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany

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M Luster Department of Nuclear Medicine, University Hospital Marburg, Marburg, Germany

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R Navardauskaitė Department of Endocrinology, Lithuanian University of Health Sciences, Kaunas, Lithuania

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M Negre Busó Nuclear Medicine Service - Institut de diagnòstic per la Imatge, Hospital Universitari de Girona Dr. Josep Trueta, Girona, Spain

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K Newbold Thyroid Therapy Unit, The Royal Marsden NHS Foundation Trust Hospital, London, UK

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R P Peeters Academic Center For Thyroid Disease, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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G Pellegriti Endocrinology, Endocrinology Division, Garibaldi-Nesima Medical Center, Catania, Italy

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A Piccardo Department of Nuclear Medicine, EO Ospedali Galliera, Genoa, Italy

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A L Priego Department of Medicine, Division of Endocrinology, Leiden, University medical Center, Leiden, The Netherlands

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A Redlich Pediatric Oncology Department, Otto von Guericke University Children's Hospital, Magdeburg, Germany

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L de Sanctis Regina Margherita Children Hospital - Department of Public Health and Pediatric Sciences, University of Torino, Torino, Italy

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M Sobrinho-Simões University Hospital of São João, Medical Faculty and Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal

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A S P van Trotsenburg Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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F A Verburg Department of Radiology & Nuclear Medicine, Erasmus MC Rotterdam, Rotterdam, The Netherlands

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M Vriens Department of Endocrine Surgery, University Medical Center Utrecht, Utrecht, The Netherlands

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T P Links Department of Endocrinology, University Medical Center Groningen, Groningen, The Netherlands

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S F Ahmed Endocrinology, Endocrinology Division, Garibaldi-Nesima Medical Center, Catania, Italy
Developmental Endocrinology Research Group, Royal Hospital for Children, University of Glasgow, Glasgow, UK
Office for Rare Conditions, University of Glasgow, Glasgow, UK

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H M van Santen Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital/ University Medical Center Utrecht, Utrecht, The Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

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studies. The development of a patient registry is a complex process which can globally be divided into three major stages: i) preparatory phase, ii) implementation, and iii) output. The ped-DTC registry is in progress, and we are currently in the

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Heleen I Jansen Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands

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Marijn M Bult Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands

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Peter H Bisschop Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Endocrinology and Metabolism, Amsterdam, The Netherlands

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Anita Boelen Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands

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Annemieke C Heijboer Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands

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Jacquelien J Hillebrand Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands

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Introduction

In our hospital, physicians noticed high free thyroxine (fT4) concentrations without complete suppression of thyroid-stimulating hormone (TSH) in blood samples of patients at the outpatient clinic, which appeared to occur more often following the introduction of a new fT4 immunoassay. This discordance may be explained by incorrect reference intervals, analytical issues, or patient-related factors. We aimed to establish the contribution of the possible factors involved.

Methods

Reference intervals of both fT4 immunoassays were re-evaluated using blood samples of healthy volunteers and the new immunoassay’s performance was assessed using internal quality controls and external quality rounds. The frequency of discordant fT4 and TSH pairings obtained from laboratory requests were retrospectively analysed using a Delfia (n = 3174) and Cobas cohort (n = 3408). Last, a literature search assessed whether the time of blood draw and the time of levothyroxine (L-T4) ingestion may contribute to higher fT4 concentrations in L-T4 users.

Results

The original reference intervals of both fT4 immunoassays were confirmed and no evidence for analytical problems was found. The Delfia (n = 176, 5.5%) and Cobas cohorts (n = 295, 8.7%) showed comparable frequencies of discordance. Interestingly, 72–81% of the discordant results belonged to L-T4 users. Literature indicated the time of blood withdrawal of L-T4 users and, therefore, the time of L-T4 intake as possible explanations.

Conclusions

High fT4 without suppressed TSH concentrations can mainly be explained by L-T4 intake. Physicians and laboratory specialists should be aware of this phenomenon to avoid questioning the assay’s performance or unnecessarily adapting the L-T4 dose in patients.

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Qian Yang Department of Endocrinology, Fifth People’s Hospital of Shanghai Fudan University, Shanghai, China

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Wencai Ke Department of Clinical Laboratory Medicine, Fifth People's Hospital of Shanghai Fudan University, Shanghai, China

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Fanfan Pan Department of Endocrinology, Fifth People’s Hospital of Shanghai Fudan University, Shanghai, China

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Xinmei Huang Department of Endocrinology, Fifth People’s Hospital of Shanghai Fudan University, Shanghai, China

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Jun Liu Department of Endocrinology, Fifth People’s Hospital of Shanghai Fudan University, Shanghai, China

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Bingbing Zha Department of Endocrinology, Fifth People’s Hospital of Shanghai Fudan University, Shanghai, China

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small number of participants (only 29 of GD individuals had neutropenia) and may not have carried sufficient statistical power to determine potential risk factors for the development of neutropenia. In our study, 1000 patients diagnosed with GD were

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Kjersti S Bakken Women’s Clinic, Innlandet Hospital Trust, Lillehammer, Norway
Center for International Health, University of Bergen, Bergen, Norway

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Kristina Randjelovic Nermo Center for International Health, University of Bergen, Bergen, Norway
Department of Microbiology, Innlandet Hospital Trust, Lillehammer, Norway

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Bjørn Gunnar Nedrebø Department of Medicine, Haugesund Hospital, Haugesund, Norway
Department of Clinical Science, University of Bergen, Bergen, Norway

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Tim I M Korevaar Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands

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Tor A Strand Center for International Health, University of Bergen, Bergen, Norway
Department of Research, Innlandet Hospital Trust, Lillehammer, Norway

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Background Optimal thyroid function during pregnancy is essential for both the mother and the developing fetus since thyroid hormones regulate the metabolism, growth, maintenance of pregnancy and development of the fetal CNS ( 1 ). During

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Fei Wu Department of Nuclear Medicine, Yancheng City No. 1 People’s Hospital, Yancheng, China
Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

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Chaoming Mao Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

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Xiao Mou Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

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Chengcheng Xu Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

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Tingting Zheng Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

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Ling Bu Department of Clinical Medicine, Jiangsu Health Vocational College, Nanjing, China

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Xuan Luo Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

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Qingyan Lu Department of Laboratory Medicine, Xuzhou Central Hospital, Xuzhou, China

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Xuefeng Wang Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

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shown that HT development depends on an immune defect in an individual with genetic susceptibility together with environmental factors ( 2 ), such as iodine, selenium, smoking, and medications (e.g. amiodarone, alumtuzumab, iplimumab, interferon alpha

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Brenda Anguiano Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro, México

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Carlos Montes de Oca Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro, México

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Evangelina Delgado-González Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro, México

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Carmen Aceves Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro, México

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Introduction The purpose of this review is to compile and discuss findings related to the role of thyroid hormones (THs) in the development, physiology, and pathology of the prostate gland. The study of the prostate is of interest in the field

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Hui Li Department of Thyroid Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, P. R. China.

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Peng Wu Department of Thyroid Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, P. R. China.

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circular RNAs (circRNAs) ( 5 , 6 , 7 ). These epigenetic processes are essential for elucidating the intricate mechanisms underlying the development and progression of thyroid cancer. Furthermore, the study of these epigenetic pathways holds significant

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Katica Bajuk Studen Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

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Simona Gaberšček Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

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Edvard Pirnat Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia

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Nataša Bedernjak Bajuk Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia

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Andreja Vendramin Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia

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Vito Majcen Department of Nuclear Medicine, SB Celje, Celje, Slovenia

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Katja Zaletel Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

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stimulation 422.5 ± 14.7 (range 400–444) nmol/L. The development of adrenal insufficiency significantly correlated with cortisol level after stimulation at visit 1 ( Fig. 5 ). No other significant difference in patients’ age, BMI, thyroid volume, basal

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Dongyan Han Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

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Min Ding Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Rongli Xie Department of General Surgery, RuiJin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Zhengshi Wang Thyroid Center, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
Shanghai Center of Thyroid Diseases, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

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Guohui Xiao Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Xiaohong Wang Shanghai Rigen Biotechnology Co., Ltd. Shanghai, China

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Lei Dong Department of Pathology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Zhiqiang Yin Thyroid Center, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
Shanghai Center of Thyroid Diseases, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

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Jian Fei Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, China
Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China

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approximately 2–3% of all thyroid cancers and is predominantly sporadic (around 80%). Point mutations are the predominant type of RET in MTC ( 19 ), while normal thyroid development does not depend on RET protein expression ( 20 ). Specific RET germline

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Kim Magaly Pabst Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, Essen, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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Robert Seifert Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, Essen, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany
Department of Nuclear Medicine, University Hospital Münster, Münster, Germany

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Nader Hirmas Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, Essen, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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Martina Broecker-Preuss Department of Medicine, Ruhr-University Bochum, University Hospital, Knappschaftskrankenhaus Bochum, Bochum, Germany

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Manuel Weber Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, Essen, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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Wolfgang Peter Fendler Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, Essen, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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Timo Bartel Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, Essen, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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Sarah Theurer German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany
Institute of Pathology, University Hospital Essen, University Duisburg-Essen, Essen, Germany

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Ken Herrmann Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, Essen, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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Rainer Görges Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, Essen, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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Objective

Recurrence of differentiated thyroid cancer (DTC) is associated with reduced quality of life, and therefore, early identification of patients at risk is urgently needed.Here we investigated the predictive power of various cut-off values of single stimulated thyroglobulin (s-Tg) and single highly sensitive measured, unstimulated thyroglobulin (u-hsTg) measurements close to the end of primary therapy for recurrence-free survival (RFS) in long-term follow-up (>10 years) of patients with DTC.

Methods

In DTC patients with adjuvant radioiodine therapy, we assessed retrospectively u-hsTg (6 ± 3 months before s-Tg measurement) and s-Tg measurements (≤24 months after last radioiodine therapy). Positive predictive (PPV)/negative predictive values (NPV) of various cut-off values (s-Tg: 0.5/1.0 ng/mL; u-hsTg: 0.09/0.2 ng/mL) for patient outcomes as well as additional factors associated with disease development were analyzed.

Results

In total, 175 patients were retrospectively reviewed (tumor recurrence: n = 14/complete remission: n = 161). Examined cut-off values for s-Tg and u-hsTg showed significant predictive power for RFS (log-rank: all P < 0.001). NPV/PPV for s-Tg were 98.6%/36.4%, respectively (0.5 ng/mL cut-off) and 96.7%/42.9%, respectively (1.0 ng/mL cut-off); those for u-hsTg were 97.3%/35.7%, respectively (0.09 ng/mL cut-off) and 95.2%/85.7%, respectively (0.2 ng/mL cut-off). U-hsTg (P < 0.001) and patient age (P < 0.05) were significantly associated with tumor recurrence. One-third of patients with tumor recurrence in the course initially showed undetectable u-hsTg after completion of primary therapy.

Conclusion

With >10 years of follow-up, both s-Tg and u-hsTg have a comparably high predictive power for RFS, while only u-hsTg was significantly associated with a recurrence event.Serial u-hsTg measurements seem warranted since patients with tumor recurrence during follow-up may have an undetectable tumor marker at baseline.

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