Search Results

You are looking at 1 - 10 of 11 items for

  • Author: Dagmar Fuhrer x
Clear All Modify Search
Dagmar Führer Department of Endocrinology and Metabolism, University Hospital Essen, University Duisburg-Essen, Essen, Germany

Search for other papers by Dagmar Führer in
Google Scholar
PubMed
Close
,
Klaudia Brix Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany

Search for other papers by Klaudia Brix in
Google Scholar
PubMed
Close
, and
Heike Biebermann Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany

Search for other papers by Heike Biebermann in
Google Scholar
PubMed
Close

Thyroid hormones (TH) are of crucial importance for the physiological function of almost all organs. In cases of abnormal TH signaling, pathophysiological consequences may arise. The routine assessment of a healthy or diseased thyroid function state is currently based on the determination of serum concentrations of thyroid-stimulating hormone (TSH), and the TH T<sub>3</sub> and T<sub>4</sub>. However, the definition of a ‘normal' TSH range and similarly ‘normal' T<sub>3</sub> and T<sub>4</sub> concentrations remains the subject of debate in different countries worldwide and has important implications on patient treatment in clinics. Not surprisingly, a significant number of patients whose thyroid function tests are biochemically determined to be within the normal range complain of impaired well-being. The reasons for this are so far not fully understood, but it has been recognized that thyroid function status needs to be ‘individualized' and extended beyond simple TSH measurement. Thus, more precise and reliable parameters are required in order to optimally define the healthy thyroid status of an individual, and as a perspective to employ these in clinical routine. With the recent identification of new key players in TH action, a more accurate assessment of a patient's thyroid status may in the future become possible. Recently described distinct TH derivatives and metabolites, TH transporters, nongenomic TH effects (either through membrane-bound or cytosolic signaling), and classical nuclear TH action allow for insights into molecular and cellular preconditions of a healthy thyroid state. This will be a prerequisite to improve management of thyroid dysfunction, and additionally to prevent and target TH-related nonthyroid disease.

Free access
Tim Brandenburg Department of Endocrinology, Diabetes and Metabolism, Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Endocrine Tumour Center at West German Cancer Center, Member of ENDO-ERN and EURACAN, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

Search for other papers by Tim Brandenburg in
Google Scholar
PubMed
Close
,
Philipp Muchalla Department of Endocrinology, Diabetes and Metabolism, Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Endocrine Tumour Center at West German Cancer Center, Member of ENDO-ERN and EURACAN, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

Search for other papers by Philipp Muchalla in
Google Scholar
PubMed
Close
,
Sarah Theurer Endocrine Tumour Center at West German Cancer Center, Member of ENDO-ERN and EURACAN, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
University Duisburg-Essen, Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

Search for other papers by Sarah Theurer in
Google Scholar
PubMed
Close
,
Kurt Werner Schmid Endocrine Tumour Center at West German Cancer Center, Member of ENDO-ERN and EURACAN, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
University Duisburg-Essen, Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

Search for other papers by Kurt Werner Schmid in
Google Scholar
PubMed
Close
, and
Dagmar Führer Department of Endocrinology, Diabetes and Metabolism, Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Endocrine Tumour Center at West German Cancer Center, Member of ENDO-ERN and EURACAN, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

Search for other papers by Dagmar Führer in
Google Scholar
PubMed
Close

Introduction: Primary squamous cell carcinoma (PSCC) of the thyroid is an exceptionally rare malignancy accounting for <1% of all primary thyroid cancers. Therapy is multimodal including surgery, radiotherapy, and chemotherapy but with no consensus for management and therapy. Here, we describe a case of a male patient who presented with a BRAF V600E-mutated PSCC of the thyroid gland showing response to combined dabrafenib and trametinib therapy over a period of >12 months. Case Presentation: A 78-year-old male patient presented with a 3-week history of dysphonia and dyspnoea. Laryngoscopy revealed a mechanical obstruction by a right-sided, subglottical mass, which on cervical ultrasound was highly suggestive of anaplastic thyroid carcinoma. Additional workup including esophagogastroduodenoscopy showed compression of the oesophagus but no oesophageal infiltration by the tumour. Immunohistochemistry displayed CK19-positive cells indicating epithelial origin of the tumour. CK5/6 and P40 immunohistochemistry confirmed the morphological impression of squamous cell differentiation while staining with thyroid markers TTF-1 and TPO was negative and PAX8 showed a nuclear positive signal. Based on immunohistopathology, presence of TP53 and BRAF V600E mutations, and exclusion of metastatic squamous cell carcinoma of other origin, the diagnosis of a PSCC of the thyroid was established. As an individualized treatment concept, we decided to advocate combined BRAF V600E targeting by the multikinase inhibitors dabrafenib and trametinib. This led to drastic improvement in patient’s quality of life without severe side effects over a period of >12 months. Conclusion: In this case, molecular diagnosis allowed a highly individualized treatment concept with combined dabrafenib and trametinib therapy.

Free access
Denise Zwanziger Department of Endocrinology and Metabolism and Division of Laboratory Research, University Hospital Essen, Essen, Germany

Search for other papers by Denise Zwanziger in
Google Scholar
PubMed
Close
,
Helena Rakov Department of Endocrinology and Metabolism and Division of Laboratory Research, University Hospital Essen, Essen, Germany

Search for other papers by Helena Rakov in
Google Scholar
PubMed
Close
,
Kathrin Engels Department of Endocrinology and Metabolism and Division of Laboratory Research, University Hospital Essen, Essen, Germany

Search for other papers by Kathrin Engels in
Google Scholar
PubMed
Close
,
Lars C. Moeller Department of Endocrinology and Metabolism and Division of Laboratory Research, University Hospital Essen, Essen, Germany

Search for other papers by Lars C. Moeller in
Google Scholar
PubMed
Close
, and
Dagmar Führer Department of Endocrinology and Metabolism and Division of Laboratory Research, University Hospital Essen, Essen, Germany

Search for other papers by Dagmar Führer in
Google Scholar
PubMed
Close

Background: In the liver the tight junction protein claudin-1 plays an important role in bile secretion by maintaining the paracellular barrier of bile canaliculi and the bile duct. A diminished bile excretion has been found in hypothyroid patients, and the prevalence of gallstones is increased in hypothyroidism. This association, however, only applies for men and is in contrast to the well-established female preponderance of biliary disease in the general population. Objectives: We hypothesized that hypothyroidism could lead to altered claudin-1 expression in the liver, and that this effect may be sex specific. Methods: We characterized claudin-1 expression and localization in livers of euthyroid and hypothyroid male and female C57BL/6NTac mice by real-time PCR, Western blot and immunofluorescence. Results: Claudin-1 is expressed in canalicular regions and the bile ducts of the murine liver. Livers of female mice showed lower claudin-1 expression than male livers. In hypothyroid livers, female animals showed an elevated claudin-1 expression, whereas reduced claudin-1 expression was found in male animals compared to the euthyroid controls. Conclusion: We demonstrate a correlation between claudin-1 expression and hypothyroidism in the murine liver. Furthermore, a sex-dependent alteration of claudin-1 expression was found.

Free access
Kathrin Engels Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany

Search for other papers by Kathrin Engels in
Google Scholar
PubMed
Close
,
Helena Rakov Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany

Search for other papers by Helena Rakov in
Google Scholar
PubMed
Close
,
Denise Zwanziger Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany

Search for other papers by Denise Zwanziger in
Google Scholar
PubMed
Close
,
Lars C. Moeller Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany

Search for other papers by Lars C. Moeller in
Google Scholar
PubMed
Close
,
Georg Homuth Department of Functional Genomics, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany

Search for other papers by Georg Homuth in
Google Scholar
PubMed
Close
,
Josef Köhrle Institute of Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany

Search for other papers by Josef Köhrle in
Google Scholar
PubMed
Close
,
Klaudia Brix Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany

Search for other papers by Klaudia Brix in
Google Scholar
PubMed
Close
, and
Dagmar Führer Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany

Search for other papers by Dagmar Führer in
Google Scholar
PubMed
Close

Background: Clinical features of thyroid dysfunction vary with age, and an oligosymptomatic presentation of hyperthyroidism is frequently observed in the elderly. This suggests age modulation of thyroid hormone (TH) action, which may occur, for example, by alterations in TH production, metabolism and/or TH action in target organs. Objectives: In this paper, we address possible changes in TH transporter expression in liver tissues as a mechanism of age-dependent variation in TH action. Methods: Chronic hyperthyroidism was induced in 4- and 20-month-old C57BL6/NTac male mice (n = 8-10) by intraperitoneal injections of 1 µg/g body weight <smlcap>L</smlcap>-thyroxine (T<sub>4</sub>) every 48 h over 7 weeks. Control animals were injected with PBS. Total RNA was isolated from liver samples for analysis of the TH transporter and TH-responsive gene expression. TH concentrations were determined in mice sera. Results: Baseline serum free T<sub>4</sub> (fT<sub>4</sub>) concentrations were significantly higher in euthyroid young compared to old mice. T<sub>4</sub> treatment increased total T<sub>4</sub>, fT<sub>4</sub> and free triiodothyronine to comparable concentrations in young and old mice. In the euthyroid state, TH transporter expression was significantly higher in old than in young mice, except for Mct8 and Oatp1a1 expression levels. Hyperthyroidism resulted in upregulation of Mct10, Lat1 and Lat2 in liver tissue, while Oatp1a1, Oatp1b2 and Oatp1a4 expression was downregulated. This effect was preserved in old animals. Conclusion: Here, we show age-dependent differences in TH transporter mRNA expression in the euthyroid and hyperthyroid state of mice focusing on the liver as a classical TH target organ.

Free access
Lars C. Moeller Department of Endocrinology and Metabolism, University of Duisburg-Essen, Essen, Germany

Search for other papers by Lars C. Moeller in
Google Scholar
PubMed
Close
,
Yaw Appiagyei-Dankah Medical University of South Carolina, Charleston, S.C., USA

Search for other papers by Yaw Appiagyei-Dankah in
Google Scholar
PubMed
Close
,
Birgit Köhler Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany

Search for other papers by Birgit Köhler in
Google Scholar
PubMed
Close
,
Heike Biebermann Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany

Search for other papers by Heike Biebermann in
Google Scholar
PubMed
Close
,
Onno E. Janssen Department of Endocrinology and Metabolism, University of Duisburg-Essen, Essen, Germany

Search for other papers by Onno E. Janssen in
Google Scholar
PubMed
Close
, and
Dagmar Führer Department of Endocrinology and Metabolism, University of Duisburg-Essen, Essen, Germany

Search for other papers by Dagmar Führer in
Google Scholar
PubMed
Close

Background: Thyroxine-binding globulin (TBG) is the main transport protein for T<sub>4</sub> in blood. Until now, 22 mutations leading to complete TBG deficiency (TBG-CD) have been reported. Objective: We report two mutations associated with TBG-CD found in patients from Andrews, S.C., USA (TBG-CD-Andrews), and Berlin, Germany (TBG-CD-Berlin). Methods: Automated chemiluminescence immunoassays were used for the determination of TSH, free and total T<sub>4</sub> and T<sub>3</sub> (fT<sub>4</sub>, TT<sub>4</sub>, TT<sub>3</sub>) and TBG. Direct DNA sequencing was used to identify the TBG mutations in the propositi. Results: TBG-CD-Andrews was found in a 1-month-old boy who was euthyroid with normal TSH and fT<sub>4</sub>, but reduced TT<sub>4</sub>, indicating TBG deficiency. TBG was not detectable, confirming TBG-CD. No mutation in the coding region and the promoter of the TBG gene was found, but a single nucleotide substitution in intron 1 disrupts the donor splice site of exon 0 (IVS1+2T>C). Another mutation was found in an 11-year-old boy. He was also euthyroid with normal fT<sub>4</sub> and TSH. However, TT<sub>4</sub> and TT<sub>3</sub> were low, suggesting TBG-CD. Sequencing revealed a 79-nucleotide deletion, ranging from intron 3 into exon 3. Conclusion: We report two novel mutations of the TBG gene associated with TBG-CD. Whereas most TBG-CDs are caused by small deletions, in TBG-CD-Andrews the disruption of a donor splice site was detected, whilst in TBG-CD-Berlin the largest deletion in the Serpina7 gene to date was found.

Free access
Beatrice Engelmann Interfaculty Institute for Genetics and Functional Genomics, Germany

Search for other papers by Beatrice Engelmann in
Google Scholar
PubMed
Close
,
Julia Bischof Interfaculty Institute for Genetics and Functional Genomics, Germany

Search for other papers by Julia Bischof in
Google Scholar
PubMed
Close
,
Anne-Luise Dirk Experimental and Clinical Endocrinology, Med Clinic I, University of Lübeck, Lübeck, Germany

Search for other papers by Anne-Luise Dirk in
Google Scholar
PubMed
Close
,
Nele Friedrich Institute for Clinical Chemistry and Laboratory Medicine, Germany

Search for other papers by Nele Friedrich in
Google Scholar
PubMed
Close
,
Elke Hammer Interfaculty Institute for Genetics and Functional Genomics, Germany

Search for other papers by Elke Hammer in
Google Scholar
PubMed
Close
,
Thomas Thiele Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany

Search for other papers by Thomas Thiele in
Google Scholar
PubMed
Close
,
Dagmar Führer Clinic for Endocrinology and Metabolic Disorders, University Clinics Essen, Essen, Germany

Search for other papers by Dagmar Führer in
Google Scholar
PubMed
Close
,
Georg Homuth Interfaculty Institute for Genetics and Functional Genomics, Germany

Search for other papers by Georg Homuth in
Google Scholar
PubMed
Close
,
Georg Brabant Experimental and Clinical Endocrinology, Med Clinic I, University of Lübeck, Lübeck, Germany

Search for other papers by Georg Brabant in
Google Scholar
PubMed
Close
, and
Uwe Völker Interfaculty Institute for Genetics and Functional Genomics, Germany

Search for other papers by Uwe Völker in
Google Scholar
PubMed
Close

Background: Hyperthyroidism is known to induce a hypercoagulable state. It stimulates plasma levels of procoagulative factors and reduces fibrinolytic activity. So far most of the data have been derived from patients with endogenous hyperthyroidism with a wide variability in the underlying pathogenesis and severity of the disease. Objectives: In this study we experimentally induced thyrotoxicosis in healthy volunteers to explore the effects of thyroxine excess on the plasma proteome. Using a shotgun proteomics approach, the abundance of plasma proteins was monitored before, during and after thyrotoxicosis. Methods: Sixteen healthy male subjects were sampled at baseline, 4 and 8 weeks under 250 µg/day thyroxine p.o., as well as 4 and 8 weeks after stopping the application. Plasma proteins were analyzed after depletion of 6 high-abundance proteins (MARS6) by LC-ESI-MS/MS mass spectrometry. Mass spectrometric raw data were processed using a label-free, intensity-based workflow. Subsequently, the linear dependence between protein abundances and fT<sub>4</sub> levels were calculated using a Pearson correlation. Results: All subjects developed biochemical thyrotoxicosis, and this effect was reversed within the first 4 weeks of follow-up. None of the volunteers noticed any subjective symptoms. Levels of 10 proteins involved in the coagulation cascade specifically correlated with fT<sub>4</sub>, supporting an influence of thyroid hormone levels on blood coagulation even at nonpathological levels. Conclusions: The results suggest that experimental thyrotoxicosis exerts selective and specific thyroxine-induced effects on coagulation markers. Our study design allows assessment of thyroid hormone effects on plasma protein levels without secondary effects of other diseases or therapies.

Free access
Joanna Szumska Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany

Search for other papers by Joanna Szumska in
Google Scholar
PubMed
Close
,
Maria Qatato Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany

Search for other papers by Maria Qatato in
Google Scholar
PubMed
Close
,
Maren Rehders Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany

Search for other papers by Maren Rehders in
Google Scholar
PubMed
Close
,
Dagmar Führer Department of Endocrinology and Metabolism and Division of Laboratory Research, University of Duisburg-Essen, Essen, Germany

Search for other papers by Dagmar Führer in
Google Scholar
PubMed
Close
,
Heike Biebermann Institut für Experimentelle Pädiatrische Endokrinologie, Berlin, Germany

Search for other papers by Heike Biebermann in
Google Scholar
PubMed
Close
,
David K. Grandy Department of Physiology and Pharmacology, School of Medicine and the Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oreg., USA

Search for other papers by David K. Grandy in
Google Scholar
PubMed
Close
,
Josef Köhrle Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany

Search for other papers by Josef Köhrle in
Google Scholar
PubMed
Close
, and
Klaudia Brix Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany

Search for other papers by Klaudia Brix in
Google Scholar
PubMed
Close

Background: The trace amine-associated receptor 1 (Taar1) is one member of the Taar family of G-protein-coupled receptors (GPCR) accepting various biogenic amines as ligands. It has been proposed that Taar1 mediates rapid, membrane-initiated effects of thyronamines, the endogenous decarboxylated and deiodinated relatives of the classical thyroid hormones T<sub>4</sub> and T<sub>3</sub>. Objectives: Although the physiological actions of thyronamines in general and 3-iodothyronamine (T<sub>1</sub>AM) in particular are incompletely understood, studies published to date suggest that synthetic T<sub>1</sub>AM-activated Taar1 signaling antagonizes thyromimetic effects exerted by T<sub>3</sub>. However, the location of Taar1 is currently unknown. Methods: To fill this gap in our knowledge we employed immunofluorescence microscopy and a polyclonal antibody to detect Taar1 protein expression in thyroid tissue from Fisher rats, wild-type and taar1-deficient mice, and in the polarized FRT cells. Results: With this approach we found that Taar1 is expressed in the membranes of subcellular compartments of the secretory pathway and on the apical plasma membrane of FRT cells. Three-dimensional analyses further revealed Taar1 immunoreactivity in cilial extensions of postconfluent FRT cell cultures that had formed follicle-like structures. Conclusions: The results suggest Taar1 transport along the secretory pathway and its accumulation in the primary cilium of thyrocytes. These findings are of significance considering the increasing interest in the role of cilia in harboring functional GPCR. We hypothesize that thyronamines can reach and activate Taar1 in thyroid follicular epithelia by acting from within the thyroid follicle lumen, their potential site of synthesis, as part of a nonclassical mechanism of thyroid autoregulation.

Free access
Laura Fugazzola Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

Search for other papers by Laura Fugazzola in
Google Scholar
PubMed
Close
,
Rossella Elisei Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Search for other papers by Rossella Elisei in
Google Scholar
PubMed
Close
,
Dagmar Fuhrer Department of Endocrinology, Diabetes and Metabolism, Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Duisburg, Germany

Search for other papers by Dagmar Fuhrer in
Google Scholar
PubMed
Close
,
Barbara Jarzab Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Institute, Oncology Center, Gliwice Branch, Gliwice, Poland

Search for other papers by Barbara Jarzab in
Google Scholar
PubMed
Close
,
Sophie Leboulleux Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy and Université Paris Saclay, Villejuif, France

Search for other papers by Sophie Leboulleux in
Google Scholar
PubMed
Close
,
Kate Newbold Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom

Search for other papers by Kate Newbold in
Google Scholar
PubMed
Close
, and
Jan Smit Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

Search for other papers by Jan Smit in
Google Scholar
PubMed
Close

The vast majority of thyroid cancers of follicular origin (TC) have a very favourable outcome, but 5–10% of cases will develop metastatic disease. Around 60–70% of this subset, hence less than 5% of all patients with TC, will become radioiodine refractory (RAI-R), with a significant negative impact on prognosis and a mean life expectancy of 3–5 years. Since no European expert consensus or guidance for this challenging condition is currently available, a task force of TC experts was nominated by the European Thyroid Association (ETA) to prepare this document based on the principles of clinical evidence. The task force started to work in September 2018 and after several revision rounds, prepared a list of recommendations to support the treatment and follow-up of patients with advanced TC. Criteria for advanced RAI-R TC were proposed, and the most appropriate diagnostic tools and the local, systemic and palliative treatments are described. Systemic therapy with multikinase inhibitors is fully discussed, including recommendations on how to start it and at which dosage, on the duration of treatment, and on the management of side effects. The appropriate relationship between the specialist and the patient/family as well as ethical issues are covered. Based on the available studies and on personal experience, the experts provided 39 recommendations aimed to improve the management of advanced RAI-R TCs. Above all of them is the indication to treat and follow these patients in a specialized setting which allows the interaction between several specialists in a multidisciplinary team.

Free access
Furio Pacini Section of Endocrinology, University of Siena, Siena, Italy

Search for other papers by Furio Pacini in
Google Scholar
PubMed
Close
,
Dagmar Fuhrer Department of Endocrinology, Diabetes and Metabolism, West German Cancer Centre (WTZ), University Hospital Essen, University Duisburg-Essen, Essen, Germany

Search for other papers by Dagmar Fuhrer in
Google Scholar
PubMed
Close
,
Rossella Elisei Section of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Search for other papers by Rossella Elisei in
Google Scholar
PubMed
Close
,
Daria Handkiewicz-Junak Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland

Search for other papers by Daria Handkiewicz-Junak in
Google Scholar
PubMed
Close
,
Sophie Leboulleux Gustave Roussy Cancer Campus and University Paris-Saclay, Villejuif, Cedex, France

Search for other papers by Sophie Leboulleux in
Google Scholar
PubMed
Close
,
Markus Luster Department of Nuclear Medicine, University Hospital Marburg, Marburg, Germany

Search for other papers by Markus Luster in
Google Scholar
PubMed
Close
,
Martin Schlumberger Gustave Roussy Cancer Campus and University Paris-Saclay, Villejuif, Cedex, France

Search for other papers by Martin Schlumberger in
Google Scholar
PubMed
Close
, and
Johannes W Smit Radboud University Medical Center, Nijmegen, Netherlands

Search for other papers by Johannes W Smit in
Google Scholar
PubMed
Close

Modern use of post-operative radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC) should be implemented in line with patients’ risk stratification. Although beneficial effects of radioiodine are undisputed in high-risk patients, controversy remains in intermediate-risk and some low-risk patients. Since the last consensus on post-surgical use of RAI in DTC patients, new retrospective data and results of prospective randomized trials have been published, which have allowed the development of a new European Thyroid Association (ETA) statement for the indications of post-surgical RAI therapy in DTC. Questions about which patients are candidates for RAI therapy, which activities of RAI can be used, and which modalities of pre-treatment patient preparation should be used are addressed in the present guidelines.

Open access
Lars Bastholt Department of Oncology R, Odense University Hospital, Odense, Denmark

Search for other papers by Lars Bastholt in
Google Scholar
PubMed
Close
,
Michael C. Kreissl Department of Nuclear Medicine, Augsburg Hospital, Augsburg
Department of Nuclear Medicine, University Hospital Würzburg, Würzburg

Search for other papers by Michael C. Kreissl in
Google Scholar
PubMed
Close
,
Dagmar Führer Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany

Search for other papers by Dagmar Führer in
Google Scholar
PubMed
Close
,
Ana L. Maia Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, Porto Alegre

Search for other papers by Ana L. Maia in
Google Scholar
PubMed
Close
,
Laura D. Locati Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan

Search for other papers by Laura D. Locati in
Google Scholar
PubMed
Close
,
Léa Maciel Hospital das Clínicas de Ribeirăo Preto, Ribeirăo Preto, Brazil

Search for other papers by Léa Maciel in
Google Scholar
PubMed
Close
,
Yi Wu Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

Search for other papers by Yi Wu in
Google Scholar
PubMed
Close
,
Kevin N. Heller AstraZeneca, Gaithersburg, Md., USA

Search for other papers by Kevin N. Heller in
Google Scholar
PubMed
Close
,
Alan Webster AstraZeneca, Macclesfield, UK

Search for other papers by Alan Webster in
Google Scholar
PubMed
Close
, and
Rossella Elisei Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Search for other papers by Rossella Elisei in
Google Scholar
PubMed
Close

Objectives: Effective management of adverse events (AEs) following vandetanib treatment is important to maximize clinical benefits. We examined whether more frequent contact with vandetanib-treated patients reduced AEs of CTCAE grade 2 or higher. Study Design: In this open-label, multicentre, phase III study, patients with locally advanced or metastatic medullary thyroid cancer were randomized to a patient outreach programme (outreach) or a standard AE monitoring schedule (vandetanib control) for 52 weeks. In addition to standard AE monitoring, patients in the outreach arm were contacted every 2 weeks by telephone/during their clinic visit for specific AE questioning related to diarrhoea, nausea, vomiting, fatigue, headache and rash. Patients received vandetanib at 200 or 300 mg/day, depending on the creatinine levels at screening. Results: Altogether, 205 patients were randomized (outreach, n = 103; vandetanib control, n = 102). This study did not meet its primary objective; the mean percentage of time patients experienced at least one AE of grade 2 or higher was higher for the outreach group (51.65%) than for the vandetanib control group (45.19%); the difference was not statistically significant (t statistic: 1.29; 95% CI -3.44 to 16.37%; p = 0.199). The most frequently reported AEs were diarrhoea (56.9% for the outreach group vs. 46.6% for the vandetanib controls), hypertension (36.3 vs. 31.1%), rash (25.5 vs. 24.3%) and nausea (25.5% vs. 18.4%), and the most frequently reported AEs of grade 2 or higher were hypertension (33.3 vs. 23.3%), diarrhoea (26.5 vs. 24.3%) and dermatitis acneiform (11.8 vs. 9.7%). Conclusions: Additional outreach to patients treated with vandetanib had no impact on the rate or severity of AEs compared to the standard AE monitoring schedule. AEs were consistent with the known safety profile of vandetanib.

Free access