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Peter D Mark Department of Medicine O, Department of Clinical Physiology and Nuclear Medicine, Department of Clinical Physiology, Faculty of Health Sciences, Center for Functional and Diagnostic Imaging and Research, Centre of Endocrinology and Metabolism, Herlev University Hospital, Herlev Ringvej 75, Herlev DK‐2730, Denmark

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Mikkel Andreassen Department of Medicine O, Department of Clinical Physiology and Nuclear Medicine, Department of Clinical Physiology, Faculty of Health Sciences, Center for Functional and Diagnostic Imaging and Research, Centre of Endocrinology and Metabolism, Herlev University Hospital, Herlev Ringvej 75, Herlev DK‐2730, Denmark

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Claus L Petersen Department of Medicine O, Department of Clinical Physiology and Nuclear Medicine, Department of Clinical Physiology, Faculty of Health Sciences, Center for Functional and Diagnostic Imaging and Research, Centre of Endocrinology and Metabolism, Herlev University Hospital, Herlev Ringvej 75, Herlev DK‐2730, Denmark
Department of Medicine O, Department of Clinical Physiology and Nuclear Medicine, Department of Clinical Physiology, Faculty of Health Sciences, Center for Functional and Diagnostic Imaging and Research, Centre of Endocrinology and Metabolism, Herlev University Hospital, Herlev Ringvej 75, Herlev DK‐2730, Denmark

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Andreas Kjaer Department of Medicine O, Department of Clinical Physiology and Nuclear Medicine, Department of Clinical Physiology, Faculty of Health Sciences, Center for Functional and Diagnostic Imaging and Research, Centre of Endocrinology and Metabolism, Herlev University Hospital, Herlev Ringvej 75, Herlev DK‐2730, Denmark
Department of Medicine O, Department of Clinical Physiology and Nuclear Medicine, Department of Clinical Physiology, Faculty of Health Sciences, Center for Functional and Diagnostic Imaging and Research, Centre of Endocrinology and Metabolism, Herlev University Hospital, Herlev Ringvej 75, Herlev DK‐2730, Denmark

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Jens Faber Department of Medicine O, Department of Clinical Physiology and Nuclear Medicine, Department of Clinical Physiology, Faculty of Health Sciences, Center for Functional and Diagnostic Imaging and Research, Centre of Endocrinology and Metabolism, Herlev University Hospital, Herlev Ringvej 75, Herlev DK‐2730, Denmark
Department of Medicine O, Department of Clinical Physiology and Nuclear Medicine, Department of Clinical Physiology, Faculty of Health Sciences, Center for Functional and Diagnostic Imaging and Research, Centre of Endocrinology and Metabolism, Herlev University Hospital, Herlev Ringvej 75, Herlev DK‐2730, Denmark

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Purpose

The aim of this study was to investigate structure and function of the heart in subclinical hyperthyroidism (SH) before and after obtaining euthyroidism by radioactive iodine treatment, using high precision and observer-independent magnetic resonance imaging (MRI) technology.

Methods

Cardiac MRI was performed before and after euthyroidism was obtained by radioactive iodine treatment in 12 otherwise healthy patients (11 women and one man, mean age 59 years, range 44–71 years) with a nodular goiter and SH, and compared with eight healthy controls investigated at baseline. Cardiac data were expressed as an index, as per body surface area, except for heart rate (HR) and ejection fraction.

Results

Post-treatment cardiac MRI was performed in median 139 days after a normalized serum TSH value had been recorded. During treatment, serum TSH increased from (median (range)) 0.01 (0.01–0.09) to 0.88 (0.27–3.99) mU/l. Patients with untreated SH had increased resting HR (P<0.01) as well as cardiac index (cardiac output as per body surface area) (P<0.01) compared with controls. Obtaining euthyroidism resulted in a significant decrease in left ventricular mass index (LVMI) of 2.7 g/m2 (P=0.034), in HR of 8 bpm (P=0.001), and in cardiac index of 0.24 l/min per m2 (P=0.017).

Conclusions

Normalization of thyroid function by radioactive iodine treatment of SH resulted in significant reductions in clinically important heart parameters such as LVMI, HR, and cardiac index. SH should be regarded as a condition in which aggressive treatment should be considered to protect cardiac function.

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Kjell Oberg Uppsala University, Uppsala, Sweden

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Eric Krenning Erasmus Medical Center, Rotterdam, Netherlands

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Anders Sundin Uppsala University, Uppsala, Sweden

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Lisa Bodei Memorial Sloan Kettering Cancer Center, New York, New York, USA

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Mark Kidd Wren Laboratories, Branford, Connecticut, USA

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Margot Tesselaar Netherlands Cancer Institute, Amsterdam, Netherlands

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Valentina Ambrosini University of Bologna, Bologna, Italy

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Richard P Baum Zentralklinik Bad Berka, Bad Berka, Germany

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Matthew Kulke Dana Farber Cancer Institute, Boston, Massachusetts, USA

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Marianne Pavel Charite Hospital, Berlin, Germany

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Jaroslaw Cwikla University of Warmia and Mazury, Olsztyn, Poland

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Ignat Drozdov Wren Laboratories, Branford, Connecticut, USA

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Massimo Falconi Ospedale San Raffaele, Milan, Italy

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Nicola Fazio IEO (European Institute of Oncology), Milan, Italy

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Andrea Frilling Imperial College London, London, UK

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Robert Jensen National Institutes of Health, Bethesda, Maryland, USA

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Klaus Koopmans Martini Ziekenhuis, Groningen, Netherlands

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Tiny Korse Netherlands Cancer Institute, Amsterdam, Netherlands

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Dik Kwekkeboom Erasmus Medical Center, Rotterdam, Netherlands

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Helmut Maecke University Hospital Freiburg, Freiburg, Germany

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Giovanni Paganelli Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy

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Ramon Salazar Instituto Catala d’Oncologia, Barcelona, Spain

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Stefano Severi Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy

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Jonathan Strosberg H. Lee Moffitt Cancer Center, Tampa, Florida, USA

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Vikas Prasad Charite Hospital, Berlin, Germany

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Aldo Scarpa University of Verona, Verona, Italy

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Ashley Grossman Univeristy of Oxford, Oxford, UK

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Annemeik Walenkamp University of Groningen, Groningen, Netherlands

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Mauro Cives H. Lee Moffitt Cancer Center, Tampa, Florida, USA

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Irene Virgolini Medical University Innsbruck, Innsbruck, Austria

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Andreas Kjaer Copenhagen University, Copenhagen, Denmark

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Irvin M Modlin Yale University, New Haven, Connecticut, USA

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The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors) criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management. Consensus (>75%) was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest) had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA) would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.

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