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Lena-Maria Levin Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany

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Henry Völzke Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
DZHK (German Centre for Cardiovascular Research), Greifswald, Germany
DZD (German Center for Diabetes Research), Greifswald, Germany

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Markus M Lerch Department of Medicine A, University Medicine Greifswald, Greifswald, Germany

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Jens-Peter Kühn Department of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany
Institute and Policlinic for Radiology and Interventional Radiology, University Hospital, Carl-Gustav-Carus University Dresden, Dresden, Germany

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Matthias Nauck Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
DZHK (German Centre for Cardiovascular Research), Greifswald, Germany

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Nele Friedrich Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
DZHK (German Centre for Cardiovascular Research), Greifswald, Germany

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Stephanie Zylla Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
DZHK (German Centre for Cardiovascular Research), Greifswald, Germany

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Objective

Chemerin and adiponectin are adipokines assumed to be involved in the development of metabolic syndrome-related phenotypes like hepatic steatosis. We aimed to evaluate the associations of circulating chemerin and adiponectin concentrations with liver enzymes, liver fat content, and hepatic steatosis in the general population.

Methods

Data of 3951 subjects from the population-based Study of Health in Pomerania (SHIP-TREND) were used. Hepatic steatosis was assumed when either a hyperechogenic liver (assessed via ultrasound) or a magnetic resonance imaging (MRI)-quantified liver fat content >5% was present. Adjusted sex-specific quantile and logistic regression models were applied to analyze the associations of chemerin and adiponectin with liver enzymes, liver fat content and hepatic steatosis.

Results

The observed associations of chemerin and adiponectin with liver enzymes were very divergent depending on sex, fasting status and the specific enzyme. More consistent results were seen in the analyses of these adipokines in relation to MRI-quantified liver fat content. Here, we observed inverse associations to adiponectin in both sexes as well as a positive (men) or U-shaped (women) association to chemerin. Similarly, the MRI-based definition of hepatic steatosis revealed strongly consistent results: in both sexes, high chemerin concentrations were associated with higher odds of hepatic steatosis, whereas high adiponectin concentrations were associated with lower odds.

Conclusion

Our results suggest a role of these adipokines in the pathogenesis of hepatic steatosis independent of metabolic or inflammatory disorders. However, experimental studies are needed to further clarify the underlying mechanisms and the inter-play between adipokine concentrations and hepatic steatosis.

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Monika Schaffner Department of Public Health, Health Services Research and Health Technology Assessment, Institute of Public Health, Medical Decision Making and Health Technology Assessment, UMIT – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria

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Ursula Rochau Department of Public Health, Health Services Research and Health Technology Assessment, Institute of Public Health, Medical Decision Making and Health Technology Assessment, UMIT – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria

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Nikolai Mühlberger Department of Public Health, Health Services Research and Health Technology Assessment, Institute of Public Health, Medical Decision Making and Health Technology Assessment, UMIT – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria

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Annette Conrads-Frank Department of Public Health, Health Services Research and Health Technology Assessment, Institute of Public Health, Medical Decision Making and Health Technology Assessment, UMIT – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria

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Vjollca Qerimi Rushaj Department of Public Health, Health Services Research and Health Technology Assessment, Institute of Public Health, Medical Decision Making and Health Technology Assessment, UMIT – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria
Faculty of Pharmacy, School of PhD Studies, Ss. Cyril and Methodius University, Skopje, Macedonia

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Gaby Sroczynski Department of Public Health, Health Services Research and Health Technology Assessment, Institute of Public Health, Medical Decision Making and Health Technology Assessment, UMIT – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria

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Eftychia Koukkou General Hospital ‘Elena Venizelou’, Athens, Greece

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Betina Heinsbaek Thuesen Centre for Clinical Research and Prevention, Capital Region of Denmark, Denmark

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Henry Völzke Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

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Wilhelm Oberaigner Department of Public Health, Health Services Research and Health Technology Assessment, Institute of Public Health, Medical Decision Making and Health Technology Assessment, UMIT – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria

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Uwe Siebert Department of Public Health, Health Services Research and Health Technology Assessment, Institute of Public Health, Medical Decision Making and Health Technology Assessment, UMIT – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria
Center for Health Decision Science, Department of Health Policy and Management, Harvard Chan School of Public Health, Boston, Massachusetts, USA
Department of Radiology, Institute for Technology Assessment, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Objective

More than 30% of the German population suffers from mild to moderate iodine deficiency causing goiter and other iodine deficiency disorders (IDDs). The economic burden of iodine deficiency is still unclear. We aimed to assess costs for prevention, monitoring and treatment of IDDs in Germany.

Design

We performed a comprehensive cost analysis.

Methods

We assessed direct medical costs and direct non-medical costs for inpatient and outpatient care of IDDs and costs for productivity loss due to the absence of work in 2018. Additionally, we calculated total costs for an IDD prevention program comprising universal salt iodization (USI). We performed threshold analyses projecting how many cases of IDDs or related treatments would need to be avoided for USI to be cost-saving.

Results

Annual average costs per case in the year of diagnosis were € 211 for goiter/thyroid nodules; € 308 for hyperthyroidism; and € 274 for hypothyroidism. Average one-time costs for thyroidectomy were € 4184 and € 3118 for radioiodine therapy. Average costs for one case of spontaneous abortion were € 916. Annual costs of intellectual disability were € 14,202. In the German population, total annual costs for USI would amount to 8 million Euro. To be cost-saving, USI would need to prevent, for example, 37,900 cases of goiter/thyroid nodules.

Conclusion

USI potentially saves costs, if a minimum amount of IDDs per year could be avoided. In order to recommend the implementation of USI, a full health-economic evaluation including a comprehensive benefit-harm assessment is needed.

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Till Ittermann Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

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Rehman Mehmood Khattak Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
Department of Zoology, Islamia College Peshawar (CU), Peshawar, Pakistan

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Marcello R P Markus Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany

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Jens-Peter Kühn Institute of Radiology, University Hospital, Carl-Gustav-Carus University, Dresden, Germany

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Marie-Luise Kromrey Department of Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany

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Giovanni Targher Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy

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Antje Steveling Department of Internal Medicine A, University Medicine Greifswald, Greifswald, Germany

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Matthias Nauck Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine, Greifswald, Germany

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Henry Völzke Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

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The associations of thyroid function parameters with non-alcoholic fatty liver disease (NAFLD) and hepatic iron overload are not entirely clear. We have cross-sectionally investigated these associations among 2734 participants of two population-based cross-sectional studies of the Study of Health in Pomerania. Serum levels of thyroid-stimulating hormone (TSH), free tri-iodothyronine (fT3), and free thyroxine (fT4) levels were measured. Liver fat content (by proton-density fat fraction) as well as hepatic iron content (by transverse relaxation rate; R2*) were assessed by quantitative MRI. Thyroid function parameters were associated with hepatic fat and iron contents by median and logistic regression models adjusted for confounding. There were no associations between serum TSH levels and liver fat content, NAFLD, or hepatic iron overload. Serum fT4 levels were inversely associated with liver fat content, NAFLD, hepatic iron contents, and hepatic iron overload. Serum fT3 levels as well as the fT3 to fT4 ratio were positively associated with hepatic fat, NAFLD, hepatic iron contents, but not with hepatic iron overload. Associations between fT3 levels and liver fat content were strongest in obese individuals, in which we also observed an inverse association between TSH levels and NAFLD. These findings might be the result of a higher conversion of fT4 to the biologically active form fT3. Our results suggest that a subclinical hyperthyroid state may be associated with NAFLD, particularly in obese individuals. Furthermore, thyroid hormone levels seem to be more strongly associated with increased liver fat content compared to hepatic iron content.

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Line Tang Møllehave Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark

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Marie Holm Eliasen Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark

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Ieva Strēle The Institute of Occupational Safety and Environmental Health, Riga Stradiņš University, Riga, Latvia

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Allan Linneberg Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Rodrigo Moreno-Reyes Nuclear Medicine Department, Erasme Hospital, Brussels, Belgium
Université Libre de Bruxelles, Bruxelles, Belgium

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Ludmila B Ivanova Faculty of Medicine, Sofia University St. Kl. Ohridski, Sofia, Bulgaria

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Zvonko Kusić Croatian Academy of Sciences and Arts, Zagreb, Croatia
School of Medicine, Zagreb, Croatia

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Iris Erlund Department of Government Services, Finnish Institute for Health and Welfare, Helsinki, Finland

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Till Ittermann Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

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Endre V Nagy Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Ingibjorg Gunnarsdottir Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland
Department of Clinical Nutrition, Landspitali-National University Hospital, Reykjavik, Iceland

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Jonathan Eli Arbelle Division of Medicine, Maccabi Healthcare Services, Tel Aviv, Israel
Goldman School of Medicine, Ben Gurion University of the Negev, Beer Sheva, Israel

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Aaron Milton Troen The Institute of Biochemistry Food Science and Nutrition, The Hebrew University of Jerusalem, Rehovot, Israel

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Valdis Pīrāgs Internal Medicine, University of Latvia, Riga, Latvia

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Lisbeth Dahl Seafood, Nutrition and Environmental State, Institute of Marine Research (IMR), Bergen, Norway

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Alicja Hubalewska-Dydejczyk Chair and Department of Endocrinology, Jagiellonian University, Medical College, Cracow, Poland

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Malgorzata Trofimiuk-Müldner Chair and Department of Endocrinology, Jagiellonian University, Medical College, Cracow, Poland

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João Jacome de Castro Endocrine Department, Armed Forces Hospital, Lisbon, Portugal

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Mafalda Marcelino Endocrine Department, Armed Forces Hospital, Lisbon, Portugal

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

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Manuel Puig-Domingo Department of Endocrinology and Nutrition, Germans Trias Research Institute and Hospital, Badalona, Spain
Universitat Autònoma de Barcelona, Barcelona, Spain

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Lluis Vila Endocrinology and Nutrition Service, Hospital Moisés Broggi, Sant Juan Despi, Barcelona, Spain

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Sofia Manousou Sahlgrenska Academy, Institute of Medicine, Gothenburg, Sweden
Frölunda Specialist Hospital, Västra Frölunda, Sweden

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Helena Filipsson Nyström Department of Endocrinology, Specialist Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Wallenberg Centre of Molecular and Translational Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden

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Michael Bruce Zimmermann Health Sciences and Technology, ETH Zurich, Zurich, Switzerland

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Karen R Mullan Regional Centre for Endocrinology and Diabetes, Belfast Health and Social Care Trust, Belfast, UK

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Jayne Valerie Woodside Centre for Public Health, Queen’s University Belfast, Belfast, UK

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Henry Völzke Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

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Betina Heinsbæk Thuesen Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark

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Objective

Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs.

Design

Register-based cross-sectional study.

Methods

National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated.

Results

Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs.

Conclusions

The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.

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