Abstracts 43Rd Annual Meeting of the European Thyroid Association
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43rd Annual Meeting of the European Thyroid Association Abstracts Virtual Conference September 4–7, 2021 Guest Editors Laszlo Hegedüs, Odense, Denmark Leonidas Duntas, Athens, Greece Abstracts containing errors in spelling, grammar, or scientific content have been published as typed by the author and have not been corrected by the Publisher Basel • Freiburg • Paris • London • New York • Chennai • New Delhi • Bangkok • Beijing • Shanghai • Tokyo • Kuala Lumpur • Singapore • Sydney Disclosure Statement Guest Editors Laszlo Hegedüs: Head of the Scientific Board and a consultant for International IBSA. Chair of the Novo Nordisk committee for Non-diabetic Endocrinology. Leonidas Duntas: Recipient of educational Grants from Merck, Berlin Chemie, and IBSA. S. Karger Disclaimer All rights reserved. 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[email protected] www.karger.com/etj Vol. 10, Suppl. 1, 2021 Contents Oral Presentations Saturday, 4th September 2021 1 Topic Highlights Sunday, 5th September 2021 3 Oral Session 1 6 Oral Session 2 Tuesday, 7th September 2021 8 Young Investigator Session / Clinical and Translational 10 Young Investigator Session / Basic 12 Oral Session 3 14 Oral Session 4 Poster Presentations September 4th–7th, 2021 17 Case Reports 18 COVID 22 Diagnostic Tools in Thyroid Cancer 23 Follow-Up in Differentiated Thyroid Carcinoma 28 Genetics 31 Iodine and Pregnancy 33 Molecular and Morphological Features in Thyroid Cancer 36 Nodules and Thyroid Cancer 39 Peripheral Actions of Thyroid Hormones 42 Primary Thyroid Disease 44 Thyroid Cell Biology 47 Thyroid Hormone Metabolites 48 Treatment of Thyroid Disease 54 Author Index E-Mail [email protected] © 2021 European Thyroid Association www.karger.com/etj Published by S. Karger AG, Basel Oral Presentations Eur Thyroid J 2021;10(suppl 1):1–56 Published online: August 6, 2021 DOI: 10.1159/000517526 Presenting authors are underlined Our scRNA-Seq for thyroid progenitors and adult TFCs points to multiple Saturday, 4th September 2021 genes with a yet unappreciated role in thyroid physiology. We hope that our efforts using the zebrafish to illuminate the process and underlying genetic network of thyroid development and maintenance might help identify candi- date genes with a role in diseases related to the thyroid. Topic Highlights 139 STATINS FOR GRAVES’ ORBITOPATHY (STAGO): 4 PRELIMINARY RESULTS OF A PHASE II ILLUMINATING THYROID DEVELOPMENT RANDOMIZED CLINICAL TRIAL AND GROWTH USING THE ZEBRAFISH Giulia Lanzolla 1, Elena Sabini 2, Marenza Leo 3, Francesca Menconi 3, MODEL SYSTEM Roberto Rocchi 3, Maria Novella Maglionico 3, Chiara Posarelli 3, Meghna Shankar 1, Macarena Pozo Morales 1, Sema Elif Eski 1, Michele Figus 3, Marco Nardi 3, Claudio Marcocci 3, Michele Marinò 3 Ines Garteizgogeascoa 1, Camille Perazzolo 1, Pierre Gillotay 2, 1University of Pisa, University of Pisa, Endocrinology Unit, Pisa, Italy; Sabine Costagliola 3, Sumeet Singh 1 2Johns Hopkins School of Medicine, Baltimore, MD, USA; 3Department 1Institute of Interdisciplinary Research in Molecular Human Biology of Clinical and Experimental Medicine, Endocrinology Units, University (Iribhm), Université Libre de Bruxelles (Belgium), Anderlecht, Belgium; of Pisa and University Hospital of Pisa 2Institute of Interdisciplinary Research in Molecular Human Biology (Iribhm), Université Libre de Bruxelles (Belgium), Iribhm, Anderlecht, Objectives: Over the past few years a role of cholesterol and statins has Belgium; 3Iribhm, Iribhm, Ulb, Brussels, Belgium emerged in Graves’ Orbitopathy (GO): a protective action of statins on the development of GO was observed in two retrospective studies; an association In the simplest form, the vertebrate thyroid gland is an iodine accumulat- between high cholesterol and GO was reported in a cross-sectional investiga- ing organ. And it does so by utilizing a structure that is conserved among tion; a worse response of GO to immunosuppressive treatment was described vertebrates: a follicle composed of epithelial tissue with a central lumen for in patients with high cholesterol levels. Based on these observations, we storage of iodinated molecules. To elucidate the fundamental processes regu- conducted the present clinical trial, designed to investigate whether adminis- lating thyroid physiology, we harness a genetically tractable vertebrate model tration of atorvastatin improves the outcome of GO to intravenous glucocor- system, the zebrafish. Zebrafish provide the advantage of transparency dur- ticoids in hypercholesterolemic patients with moderate-to-severe, active GO. ing early development, allowing direct visualization of thyroid morphogen- Methods: Eighty-eight patients with moderate-to-severe, active GO and esis and growth. Moreover, 84 per cent of genes known to be associated with high LDL-cholesterol were randomized in a 1:1 ratio into treatment with human disease have a zebrafish counterpart, allowing modeling of human intravenous methylprednisolone (500 mg/week for 6 weeks, 250 mg/week for disorders. 6 weeks) plus atorvastatin (20 mg/daily for 12 weeks) (statin group) or meth- Here, using in vivo live imaging, we demonstrate the zebrafish thyroid ylprednisolone alone (non-statin group). Patients were evaluated at baseline follicular cells (TFCs) are ciliated, polarized and surrounded by a network and then at 12 and 24 weeks. The primary endpoint was the overall outcome of of blood and lymphatic vessels. To understand the differentiation of thyroid GO at 24 weeks, assessed using a composite evaluation. The secondary end- from progenitors, we performed single-cell RNA-Seq (scRNA-Seq) of foregut points were: 1) outcome of GO at 12 weeks; 2) improvement in quality of life, endoderm at a stage when thyroid progenitors are specified, but not yet differ- using a specific questionnaire (GO-QoL) at 12 and 24 weeks; 3) GO relapse at entiated. This allowed us to compare the molecular characteristics of thyroid 24 weeks. Here we present the preliminary results obtained in 80/88 patients. progenitors with the neighboring endoderm, providing clues into regulators Results: At week 24, the proportion of responders in the intention-to-treat for thyroid specification. Using loss of function analysis, we uncover gene population was significantly higher in the statin group [48.7% vs. 23% in the regulatory network underlying thyroid morphogenesis, defects which lead to non-statin group; P=0.01). GO relapse at 24 weeks was more frequent in non- congenital hypothyroidism. statin group [15.3% vs 0% in the statin group; P=0.01]. A significant greater Moreover, using newly generated transgenic reporters for cell-cycle, we improvement in quality of life across the follow-up period was observed in the capture replicating TFCs in their native environment. Using scRNA-Seq, we statin group compared with the non-statin group (P=0.03). No significant dif- will develop an atlas of the cell-cycle in thyroid follicular cells, providing ferences were observed with the remaining secondary outcome measure (over- genes involved in goiter and cancer. all GO outcome at 12 weeks). No significant difference in LDL-cholesterol Finally, to understand maintenance of TFCs during homeostasis, we per- levels was observed across the follow-up period between GO responders and formed scRNA-Seq of the region in adult zebrafish encompassing the thyroid non-responders, suggesting that the effect of atorvastatin is likely due to its follicles. With this, we identify genes expressed in mature TFCs and the sur- anti-inflammatory actions. No severe adverse events were observed. rounding cells. Using the prolife of TFCs at cellular resolution, we identify Conclusions: Atorvastatin seems to improve