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Kevin Stroek Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Annemieke C. Heijboer Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands

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Marja van Veen-Sijne Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Annet M. Bosch Division of Metabolic Disorders, Department of Pediatrics, Emma Children’s Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Catharina P.B. van der Ploeg Department of Child Health, Netherlands Organization for Applied Scientific Research TNO, Leiden, The Netherlands

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Nitash Zwaveling-Soonawala Department of Paediatric Endocrinology, Emma Children’s Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Robert de Jonge Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit & University of Amsterdam, Amsterdam, The Netherlands

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A.S. Paul van Trotsenburg Department of Paediatric Endocrinology, Emma Children’s Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Anita Boelen Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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[ 6 ], optimization of the Dutch NBS for detection of CH-C is warranted to improve its specificity. Reference intervals (RIs) for diagnostic tests are crucial for the interpretation of the measurements. A RI is based on measurement of a laboratory test

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Marta Kostecka-Matyja Chair and Department of Endocrinology, Jagiellonian University, Collegium Medicum, Krakow

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Anna Fedorowicz Chair and Department of Endocrinology, Jagiellonian University, Collegium Medicum, Krakow

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Ewa Bar-Andziak Department of Internal Medicine and Endocrinology, Medical University, Warsaw

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Tomasz Bednarczuk Department of Internal Medicine and Endocrinology, Medical University, Warsaw

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Monika Buziak-Bereza Chair and Department of Endocrinology, Jagiellonian University, Collegium Medicum, Krakow

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Paulina Dumnicka Department of Medical Diagnostics, Jagiellonian University, Collegium Medicum, Krakow

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Maria Górska Department of Endocrinology, Diabetology and Internal Medicine, Medical University, Bialystok

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Małgorzata Krasnodębska Department of Internal Medicine and Endocrinology, Medical University, Warsaw

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Beata Niedźwiedzka Department of Internal Medicine and Endocrinology, Medical University, Warsaw

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Dorota Pach Chair and Department of Endocrinology, Jagiellonian University, Collegium Medicum, Krakow

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Marek Ruchała Department of Endocrinology, Metabolism and Internal Medicine, University of Medical Sciences, Poznan

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Katarzyna Siewko Department of Endocrinology, Diabetology and Internal Medicine, Medical University, Bialystok

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Bogdan Solnica Department of Diagnostics, Chair of Clinical Biochemistry, Jagiellonian University, Collegium Medicum, Krakow, Poland

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Jerzy Sowiński Department of Endocrinology, Metabolism and Internal Medicine, University of Medical Sciences, Poznan

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Małgorzata Szelachowska Department of Endocrinology, Diabetology and Internal Medicine, Medical University, Bialystok

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Małgorzata Trofimiuk-Müldner Chair and Department of Endocrinology, Jagiellonian University, Collegium Medicum, Krakow

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Katarzyna Wachowiak-Ochmańska Department of Endocrinology, Metabolism and Internal Medicine, University of Medical Sciences, Poznan

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Alicja Hubalewska-Dydejczyk Chair and Department of Endocrinology, Jagiellonian University, Collegium Medicum, Krakow

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secretion peak corresponds to the decrease in TSH secretion [ 11 ]. TSH levels during late pregnancy stay within the reference intervals determined for the general population, but in the first trimester it tends to be lower. The lowest TSH concentrations

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Lise Husted Department of Clinical Biochemistry, Viborg Regional Hospital, Viborg, Denmark

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Sidsel Rødgaard-Hansen Department of Clinical Biochemistry, Viborg Regional Hospital, Viborg, Denmark

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Maja Hjelm Lundgaard Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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Nanna Maria Uldall Torp Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

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Stine Linding Andersen Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

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shows considerable dynamics within the first trimester of a pregnancy which necessitates the use of pregnancy-specific reference intervals in the assessment of maternal thyroid function ( 3 ). In the kidney, an increase in renal plasma flow and the

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Bernadette Biondi Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy

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Luigi Bartalena Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, Ospedale di Circolo, Varese, Italy

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David S. Cooper Division of Endocrinology, Diabetes, and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Md., USA

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Laszlo Hegedüs Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark

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Peter Laurberg Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark

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George J. Kahaly Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany

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Endogenous subclinical hyperthyroidism (SHyper) is caused by Graves' disease, autonomously functioning thyroid nodules and multinodular goitre. Its diagnosis is based on a persistently subnormal serum thyroid-stimulating hormone (TSH) level with free thyroid hormone levels within their respective reference intervals. In 2014 the European Thyroid Association Executive Committee, given the controversies regarding the treatment of Endo SHyper, formed a task force to develop clinical practice guidelines based on the principles of evidence-based medicine. The task force recognized that recent meta-analyses, including those based on large prospective cohort studies, indicate that SHyper is associated with increased risk of coronary heart disease mortality, incident atrial fibrillation, heart failure, fractures and excess mortality in patients with serum TSH levels <0.1 mIU/l (grade 2 SHyper). Therefore, despite the absence of randomized prospective trials, there is evidence that treatment is indicated in patients older than 65 years with grade 2 SHyper to potentially avoid these serious cardiovascular events, fractures and the risk of progression to overt hyperthyroidism. Treatment could be considered in patients older than 65 years with TSH levels 0.1-0.39 mIU/l (grade 1 SHyper) because of their increased risk of atrial fibrillation, and might also be reasonable in younger (<65 years) symptomatic patients with grade 2 SHyper because of the risk of progression, especially in the presence of symptoms and/or underlying risk factors or co-morbidity. Finally, the task force concluded that there are no data to support treating SHyper in younger asymptomatic patients with grade 1 SHyper. These patients should be followed without treatment due to the low risk of progression to overt hyperthyroidism and the weaker evidence for adverse health outcomes.

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

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Antonius E van Herwaarden Radboud University Medical Center, Department of Laboratory Medicine, Nijmegen, The Netherlands

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Henk J Huijgen Department of Clinical Chemistry, Red Cross Hospital, Beverwijk, The Netherlands

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Rebecca C Painter Department of Obstetrics and Gynaecology, Amsterdam UMC Vrije Universiteit Amsterdam, 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
Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands

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

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

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comparability of the fT4 assays enabling worldwide generalized reference intervals, will improve interpretation and will prevent miscommunication regarding fT4 results. However, there are other methodological quality aspects (like matrix effects in a pregnant

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Véronique Raverot Hospices Civils de Lyon, Groupement Hospitalier Est, LBMMS, Centre de biologie et de pathologie Est, Lyon, France

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Stéphanie Metrat Hospices Civils de Lyon, Groupement Hospitalier Est, LBMMS, Centre de biologie et de pathologie Est, Lyon, France

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Pauline Perrin Hospices Civils de Lyon, Groupement Hospitalier Est, LBMMS, Centre de biologie et de pathologie Est, Lyon, France

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Juliette Abeillon Hospices Civils de Lyon, Groupement Hospitalier Est, Fédération d’Endocrinologie, Lyon, France

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Hélène Lasolle Hospices Civils de Lyon, Groupement Hospitalier Est, Fédération d’Endocrinologie, Lyon, France

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context of constitutional thinness (TSH: 63.9 mUI/L (reference interval (RI): 0.27–4.2 mUI/L), free T4: 16 pmol/L (RI: 12.51–21.39 pmol/L), and free T3: 5.8 pmol/L (RI: 3.10–6.8 pmol/L); cobas analyser, Roche Diagnostics). Anti-thyroid peroxidase and anti

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Linda M. Thienpont Mass Spectrometry Reference Laboratory, Laboratory for Analytical Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium

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James D. Faix Clinical Chemistry and Immunology, Montefiore Medical Center, New York, N.Y., USA
Department of Pathology, Albert Einstein School of Medicine, New York, N.Y., USA

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Graham Beastall International Federation of Clinical Chemistry and Laboratory Medicine, Milan, Italy

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assays to use common reference intervals or decision limits for interpretation of results. However, in view of the Committee's approach to standardization/harmonization with clinically relevant patient samples, this recalibration basis will uniquely be

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Federica D’Aurizio Department of Laboratory Medicine, Institute of Clinical Pathology, University Hospital of Udine, Udine, Italy

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Alessia Biasotto Department of Medicine, University of Udine, Udine, Italy

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Claudia Cipri Endocrinology, Metabolism and Clinical Nutrition Unit, University Hospital of Udine, Udine, Italy

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Franco Grimaldi Endocrinology, Metabolism and Clinical Nutrition Unit, University Hospital of Udine, Udine, Italy

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Jessica Zucco Department of Laboratory Medicine, Institute of Clinical Pathology, University Hospital of Udine, Udine, Italy

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Stefania Marzinotto Department of Laboratory Medicine, Institute of Clinical Pathology, University Hospital of Udine, Udine, Italy

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Francesco Curcio Department of Laboratory Medicine, Institute of Clinical Pathology, University Hospital of Udine, Udine, Italy
Department of Medicine, University of Udine, Udine, Italy

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Salvatore Benvenga Department of Clinical and Experimental Medicine, Endocrinology Section, University of Messina, Messina, Italy

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baby, coinciding with normalization of TPOAb concentrations. Because of her history, TFT were monitored during her second gestation. At week 5 + 2 days, TSH and FT4 values were normal and congruent (1.69 mIU/L, reference interval: 0.36–3.74 mIU/L; 15

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Mikael Lantz Department of Endocrinology and Ophthalmology, Skåne University Hospital Malmö, Malmö
Department of Clinical Sciences, Lund University, Lund

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Jan Calissendorff Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset

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Frank Träisk Department of Clinical Neurosciences, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden

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Leif Tallstedt Department of Clinical Neurosciences, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden

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Tereza Planck Department of Endocrinology and Ophthalmology, Skåne University Hospital Malmö, Malmö
Department of Clinical Sciences, Lund University, Lund

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Ove Törring Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset

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Bengt Hallengren Department of Endocrinology and Ophthalmology, Skåne University Hospital Malmö, Malmö
Department of Clinical Sciences, Lund University, Lund

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Peter Åsman Department of Endocrinology and Ophthalmology, Skåne University Hospital Malmö, Malmö
Department of Clinical Sciences, Lund University, Lund

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in certain periods. In general, during screening half of the patients could be included and only 6 patients were lost during the 2-year follow-up period; the study was terminated in May 2014. Assays Plasma TSH (reference interval: 0.4-3.7 mIU

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Camilla Bøgelund Larsen Department of Endocrinology, Odense University Hospital, Odense, Denmark
Department of Clinical Research, University of Southern Denmark, Odense, Denmark

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Eva Rabing Brix Petersen Department of Clinical Biochemistry and Immunology, Hospital of Southern Jutland, Aabenraa, Denmark

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Martin Overgaard Department of Clinical Research, University of Southern Denmark, Odense, Denmark
Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark

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Steen Joop Bonnema Department of Endocrinology, Odense University Hospital, Odense, Denmark
Department of Clinical Research, University of Southern Denmark, Odense, Denmark

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decreased during LT4 replacement therapy, in parallel with a rise in plasma free T4. Reference interval of TSH: 0.3–4.0 mIU/L; free T4: 12–21 pmol/L. LT4 was initiated at week = 0 and withdrawn at week = 28. LT4, levothyroxine. Supplementary

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