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Tanja Diana Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany

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Paul D. Olivo Department of Molecular Microbiology, Washington University Medical School, St. Louis, Missouri, USA

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Yie-Hwa Chang Mediomics, LLC, St. Louis, Missouri, USA

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Christian Wüster Endocrine Laboratory and Practice Prof. Wüster, Mainz, Germany

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Michael Kanitz Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany

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George J. Kahaly Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany

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) cells expressing a chimeric human TSH-R. In addition, CHO cells expressing the wild-type (WT) TSH-R and a cAMP-responsive luciferase reporter were utilized to measure TSAb [ 28 ] and TBAb [ 29 ]. These bioassays are based on the transcription of a

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Tanja Diana Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany

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Christian Wüster Endocrine Laboratory Prof. Wüster, Mainz, Germany

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Paul D. Olivo Department of Microbiology, Washington University, St. Louis, Missouri, USA

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Angelica Unterrainer Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany

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Jochem König Endocrine Laboratory Prof. Wüster, Mainz, Germany

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Michael Kanitz Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany

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Artur Bossowski Department of Pediatrics, Endocrinology, and Diabetology, Medical University of Byalistok, Bialystok, Poland

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Brigitte Decallonne Division of Clinical and Experimental Endocrinology, UZ Leuven, Leuven, Belgium

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George J. Kahaly Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany

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performance of TSHR Ab immunoassays are available, we aimed to measure the lowest possible Ab concentration in several immunoassays and to compare the performance of ELISA and automated assays. FDA-cleared and/or validated functional cell-based bioassays for

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George J. Kahaly Johannes Gutenberg University Medical Center, Mainz, Germany

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for measuring the biological activity of molecules and this has been specifically and successfully applied to TSHR-Ab [ 7 ]. TSHR bioassays are functional cell-based tests that directly assess the bioactive immunoglobulins having either stimulating or

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Tanja Diana Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany

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Hans-Peter Holthoff AdvanceCor GmbH, Martinsried, Germany

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Julia Fassbender AdvanceCor GmbH, Martinsried, Germany

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Christian Wüster Endocrine Laboratory and Practice Prof. Wüster, Mainz, Germany

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Michael Kanitz Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany

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George J. Kahaly Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany

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Martin Ungerer AdvanceCor GmbH, Martinsried, Germany

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and thyroid-related antibodies. Bioassay for Blocking TSHR Antibodies Levels of serum TSHR-blocking antibodies (TBAb) were measured according to the manufacturer’s (Quidel, San Diego, USA) instructions for the CE-marked cell-based bioassay [ 27

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Naohiro Araki Diagnostic Division, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan

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Mitsuru Iida Diagnostic Division, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan

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Nobuyuki Amino Department of Internal Medicine, Kuma Hospital, Kobe, Japan

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Shinji Morita Department of Internal Medicine, Kuma Hospital, Kobe, Japan

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Akane Ide Department of Internal Medicine, Kuma Hospital, Kobe, Japan

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Eijun Nishihara Department of Internal Medicine, Kuma Hospital, Kobe, Japan

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Mitsuru Ito Department of Internal Medicine, Kuma Hospital, Kobe, Japan

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Jun Saito Department of Medicine, Yokohama Rosai Hospital, Yokohama, Japan

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Tetsuo Nishikawa Department of Medicine, Yokohama Rosai Hospital, Yokohama, Japan

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Kiyonori Katsuragi Diagnostic Division, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan

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Akira Miyauchi Department of Internal Medicine, Kuma Hospital, Kobe, Japan

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TSBAb depend on cell-based assays using various cells such as porcine primary cells, human thyroid cells and Fischer rat thyroid cell line-5 (FRTL-5), combined with the measurement of cyclic adenosine monophosphate (cAMP) released from the cells

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Isabelle Clinckspoor Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven

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Anne-Catherine Gérard Pôle de Morphologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain

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Jacqueline Van Sande IRIBHM, Université Libre de Bruxelles, Brussels

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Marie-Christine Many Pôle de Morphologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain

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Lieve Verlinden Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven

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Roger Bouillon Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven

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Geert Carmeliet Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven

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Chantal Mathieu Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven
Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium

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Annemieke Verstuyf Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven

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Brigitte Decallonne Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven
Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium

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washed three times and the counts were recorded in a gamma counter. Serum TSH was evaluated by bioassay using a line of Chinese hamster ovary cells (CHO-K1) stably transfected with human TSH receptor cDNA, as previously described [ 30 ]. Five to eleven

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Fabio Maino Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Cristina Dalmiglio Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Nicoletta Benenati Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Michele Campanile Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Tania Pilli Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Raffaella Forleo Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Lucia Brilli Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Cristina Ciuoli Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Silvia Cantara Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Marco Capezzone Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Alessandra Cartocci Department of Medical Biotechnologies, University of Siena, Siena, Italy

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Furio Pacini Humanitas Clinical Institute, Humanitas University, Rozzano, Italy

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Maria Grazia Castagna Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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with a nodular thyroid, the measurement of basal serum CT levels has been proposed as a systematic screening method for MTC [ 2 , 3 ]. The routine measurement of CT in patients with thyroid nodules can be useful in the early diagnosis of MTC and C-cell

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

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Luigi Bartalena Department of Medicine and Surgery, University of Insubria, Varese, Italy

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

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Laurence Leenhardt Thyroid and Endocrine Tumors Unit, Pitié Salpêtrière Hospital, Sorbonne University, Paris, France

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Kris Poppe Endocrine Unit, CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium

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Simon H. Pearce Department of Endocrinology, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom

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-R-Ab concentration measured with second- and third-generation binding assays were 97 and 98%, respectively [ 25 ]. In contrast, the highly sensitive cell-based bioassays [ 26 - 33 ] exclusively differentiate between the TSH-R-stimulating Ab (TSAb) and TSH

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Sandrine Donadio-Andréi Siamed'Xpress, Hôtel Technologique Morandat, Gardanne

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Karim Chikh Hospices Civils de Lyon, Lyon
CARMEN-INSERM U1060, Université Claude Bernard Lyon 1, Faculté de Médecine et de Maïeutique Lyon Sud - Charles Mérieux, Oullins
Société Française de Médecine Nucléaire, Groupe de Biologie Spécialisée, Centre Antoine Béclère, Paris

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Christine Heuclin BioSIMS Technologies, Seine Biopolis II, Rouen

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Elisabetta Kuczewski Hospices Civils de Lyon, Lyon

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Anne Charrié Hospices Civils de Lyon, Lyon
CARMEN-INSERM U1060, Université Claude Bernard Lyon 1, Faculté de Médecine et de Maïeutique Lyon Sud - Charles Mérieux, Oullins
Société Française de Médecine Nucléaire, Groupe de Biologie Spécialisée, Centre Antoine Béclère, Paris

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Anne-Sophie Gauchez Société Française de Médecine Nucléaire, Groupe de Biologie Spécialisée, Centre Antoine Béclère, Paris
Laboratoire du Service de Médecine Nucléaire, Centre Hospitalier de Chambéry, Chambéry
Pôle de Biologie, Centre Hospitalier et Universitaire de Grenoble
UMR-S INSERM 1037, Grenoble, France

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Catherine Ronin Siamed'Xpress, Hôtel Technologique Morandat, Gardanne

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-Aldrich), pH 7.4. Cyclic AMP released from the cells was measured by RIA (Immunotech, Marseille, France). The negative sera of pooled TSH-receptor antibodies (normal sera) were used to measure cAMP basal production. Results were expressed as the ratio of

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Alan Chun Hong Lee Division of Endocrinology and Metabolism, Department of Medicine, Queen Mary Hospital, Hong Kong, China
Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany

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

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DON [ 63 ]. Based on the latest evidence, the EUGOGO recommends that RTX be considered as one of the second-line treatment options after failure of IVGC, but it should not be used in patients with impending DON or long duration of disease [ 2 ]. B cell

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