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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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MacroTSH still interferes with TSH assays. We present here a case report illustrating the difficulties that can arise in such conditions and attempt to discuss the steps involved in diagnosis.

Open access
Sara Monteiro-Martins Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany

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Rosalie B T M Sterenborg Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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Oleg Borisov Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany

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Nora Scherer Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany
Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany

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Yurong Cheng Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany

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Marco Medici Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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Anna Köttgen Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

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Alexander Teumer Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany

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Introduction

Thyroid hormones have systemic effects on the human body and play a key role in the development and function of virtually all tissues. They are regulated via the hypothalamic–pituitary–thyroid (HPT) axis and have a heritable component. Using genetic information, we applied tissue-specific transcriptome-wide association studies (TWAS) and plasma proteome-wide association studies (PWAS) to elucidate gene products related to thyrotropin (TSH) and free thyroxine (FT4) levels.

Results

TWAS identified 297 and 113 transcripts associated with TSH and FT4 levels, respectively (25 shared), including transcripts not identified by genome-wide association studies (GWAS) of these traits, demonstrating the increased power of this approach. Testing for genetic colocalization revealed a shared genetic basis of 158 transcripts with TSH and 45 transcripts with FT4, including independent, FT4-associated genetic signals within the CAPZB locus that were differentially associated with CAPZB expression in different tissues. PWAS identified 18 and ten proteins associated with TSH and FT4, respectively (HEXIM1 and QSOX2 with both). Among these, the cognate genes of five TSH- and 7 FT4-associated proteins mapped outside significant GWAS loci. Colocalization was observed for five plasma proteins each with TSH and FT4. There were ten TSH and one FT4-related gene(s) significant in both TWAS and PWAS. Of these, ANXA5 expression and plasma annexin A5 levels were inversely associated with TSH (PWAS: P = 1.18 × 10−13, TWAS: P = 7.61 × 10−12 (whole blood), P = 6.40 × 10−13 (hypothalamus), P = 1.57 × 10−15 (pituitary), P = 4.27 × 10−15 (thyroid)), supported by colocalizations.

Conclusion

Our analyses revealed new thyroid function-associated genes and prioritized candidates in known GWAS loci, contributing to a better understanding of transcriptional regulation and protein levels relevant to thyroid function.

Open access
Abdul Rehman Syed University of Calgary, Calgary, Alberta, Canada

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Aakash Gorana Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Alberta, Canada

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Erik Nohr Alberta Precision Laboratories, Molecular Pathology Program, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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Xiaoli-Kat Yuan Precision Oncology Hub Laboratory, Tom Baker Cancer Centre, Calgary, Alberta, Canada

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Parthiv Amin MASc Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary Alberta, Canada

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Sana Ghaznavi Arnie Charbonneau Cancer Institute, Department of Medicine, Section of Endocrinology, University of Calgary, Calgary, Alberta, Canada

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Debbie Lamb Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Alberta, Canada

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John McIntyre Precision Oncology Hub Laboratory, Tom Baker Cancer Centre, Calgary, Alberta, Canada

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Markus Eszlinger Department of Oncology, Cumming School of Medicine, and Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada

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Ralf Paschke Departments of Medicine, Section of Endocrinology, Oncology, Pathology and Laboratory Medicine, Biochemistry and Molecular Biology and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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Context

Two-thirds of metastatic differentiated thyroid cancer (DTC) patients have radioiodine (RAI)-resistant disease, resulting in poor prognosis and high mortality. For rare NTRK and RET fusion-positive metastatic, RAI-resistant thyroid cancers, variable success of re-induction of RAI avidity during treatment with NTRK or RET inhibitors has been reported.

Case presentation and results

We report two cases with RAI-resistant lung metastases treated with larotrectinib: an 83-year-old male presenting with an ETV6::NTRK3 fusion-positive tumor with the TERT promoter mutation c.-124C>T, and a 31-year-old female presenting with a TPR::NTRK1 fusion-positive tumor (and negative for TERT promoter mutation). Post larotrectinib treatment, diagnostic I-123 whole body scan revealed unsuccessful RAI-uptake re-induction in the TERT-positive tumor, with a thyroid differentiation score (TDS) of −0.287. In contrast, the TERT-negative tumor exhibited successful I-131 reuptake with a TDS of −0.060.

Conclusion

As observed for RAI-resistance associated with concurrent TERT and BRAF mutations, the co-occurrence of TERT mutations and NTRK fusions may also contribute to re-sensitization failure.

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

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Maurilio Deandrea Endocrinology, Diabetes and Metabolism Department and Center for Thyroid Diseases, Ordine Mauriziano Hospital, Turin, Italy

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Stefano Borgato Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Marco Dell’Acqua Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Francesca Retta Endocrinology, Diabetes and Metabolism Department and Center for Thyroid Diseases, Ordine Mauriziano Hospital, Turin, Italy

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Alberto Mormile Endocrinology, Diabetes and Metabolism Department and Center for Thyroid Diseases, Ordine Mauriziano Hospital, Turin, Italy

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Chiara Carzaniga Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Giacomo Gazzano Pathology Unit, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Gabriele Pogliaghi Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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Marina Muzza Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Luca Persani Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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Background

Radiofrequency ablation (RFA) is effective in the treatment of thyroid nodules, leading to a 50–90% reduction with respect to baseline. Current guidelines indicate the need for a benign cytology prior to RFA, though, on the other side, this procedure is also successfully used for the treatment of papillary microcarcinomas. No specific indications are available for nodules with an indeterminate cytology (Bethesda III/IV).

Aim

To evaluate the efficacy of RFA in Bethesda III nodules without genetic alterations as verified by means of a custom panel.

Methods

We have treated 33 patients (mean delivered energy 1069 ± 1201 J/mL of basal volume) with Bethesda III cytology, EU-TIRADS 3-4, and negative genetic panel. The mean basal nodular volume was 17.3 ± 10.7 mL.

Results

Considering the whole series, the mean volume reduction rate (VRR) was 36.8 ± 16.5% at 1 month, 59.9 ± 15.5% at 6 months, and 62 ± 15.7% at 1-year follow-up. The sub-analysis done in patients with 1 and 2 years follow-up data available (n = 20 and n = 5, respectively) confirmed a progressive nodular volume decrease. At all-time points, the rate of reduction was statistically significant (P < 0.0001), without significant correlation between the VRR and the basal volume. Neither cytological changes nor complications were observed after the procedure.

Conclusion

RFA is effective in Bethesda III, oncogene-negative nodules, with reduction rates similar to those obtained in confirmed benign lesions. This procedure represents a good alternative to surgery or active surveillance in this particular class of nodules, regardless of their initial volume. A longer follow-up will allow to evaluate further reduction or possible regrowth.

Open access
Sara De Vincentis Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy

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Simona Loiacono Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

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Eleonora Zanni Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

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Roberta Sueri Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

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Maria Laura Monzani Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy

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Daniele Santi Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy

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Ilaria Muller Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
Department of Endocrinology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Francesco Di Marco School of Specialisation in Endocrinology, University of Milan, Milan, Italy

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Erica Crivicich School of Specialisation in Endocrinology, University of Milan, Milan, Italy

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Mirco Armenti School of Specialisation in Endocrinology, University of Milan, Milan, Italy

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Uberto Pagotto Department of Medical and Surgical Sciences, Alma Mater Studiorum - Bologna University, Bologna, Italy
Department of Endocrinology and Diabetes Care and Prevention Unit, IRCCS Sant’Orsola-Malpighi Polyclinic, Bologna, Italy

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Lorenzo Tucci Department of Medical and Surgical Sciences, Alma Mater Studiorum - Bologna University, Bologna, Italy
Department of Endocrinology and Diabetes Care and Prevention Unit, IRCCS Sant’Orsola-Malpighi Polyclinic, Bologna, Italy

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Carolina Cecchetti Department of Medical and Surgical Sciences, Alma Mater Studiorum - Bologna University, Bologna, Italy
Department of Endocrinology and Diabetes Care and Prevention Unit, IRCCS Sant’Orsola-Malpighi Polyclinic, Bologna, Italy

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Tommaso Trenti Department of Laboratory Medicine and Anatomy Pathology, Azienda USL Modena, Modena, Italy

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Valentina Pecoraro Department of Laboratory Medicine and Anatomy Pathology, Azienda USL Modena, Modena, Italy

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Giulia Canu Department of Laboratory Medicine and Anatomy Pathology, Azienda USL Modena, Modena, Italy

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Manuela Simoni Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy

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Giulia Brigante Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy

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Objective

Many cases of subacute thyroiditis (SAT) have been described related to SARS-CoV-2 infection, but no prospective data about follow-up are known. This prospective, longitudinal, 3-year, multicentre study aims to explore the clinical peculiarities and outcome of SAT in relation to SARS-CoV-2 infection, ascertained with antibody dosage.

Methods

All patients receiving SAT diagnosis from November 2020 to May 2022 were enrolled. Data on anamnesis, physical examination, blood tests (TSH, freeT4, freeT3, thyroglobulin, anti-thyroid antibodies, C-reactive protein, erythrocyte sedimentation rate, complete blood count), and thyroid ultrasound were collected. At baseline, the presence of IgG against the SARS-CoV-2 spike protein or nucleocapsid was investigated. Patients were evaluated after 1, 3, 6, and 12 months.

Results

Sixty-six subjects were enrolled. At baseline, 54 presented with pain, 36 (67%) for at least 15 days. Serum SARS-CoV-2 IgG measurements documented that 7 out of 52 subjects (13.5%) had infection before SAT diagnosis (COVID+). No significant differences between the COVID+ and COVID− groups were found at baseline, except for respiratory symptoms and fever, which were more common in COVID+ (P = 0.039 and P = 0.021, respectively). Among the 41 subjects who completed follow-up, COVID+ and COVID− did not differ for therapeutic approach to SAT or outcome, all having an improvement in neck pain, inflammation parameters, and ultrasound features.

Conclusion

This is the first prospective study investigating any difference both at diagnosis and at follow-up between SAT presentation in patients with previous SARS-CoV-2 infection and those without. Our data demonstrate that SARS-CoV-2 does not impact on SAT onset, evolution, and outcome.

Open access
Stan R Ursem Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC Location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands

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Anita Boelen Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC Location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands

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Eveline Bruinstroop Department of Endocrinology and Metabolism, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands

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Petra J M Elders Department of General Practice, Amsterdam UMC Location Vrije Universiteit, Amsterdam, The Netherlands
Amsterdam Public Health Research Institute, Amsterdam UMC, The Netherlands

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Jacobijn Gussekloo LUMC Center for Medicine for Older People, Leiden University Medical Center, Leiden, The Netherlands
Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands

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Rosalinde K E Poortvliet LUMC Center for Medicine for Older People, Leiden University Medical Center, Leiden, The Netherlands
Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands

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Annemieke C Heijboer Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC Location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands
Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC Location Vrije Universiteit Amsterdam, Boelelaan, Amsterdam, The Netherlands

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Wendy P J den Elzen Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Laboratory Specialized Diagnostics & Research, Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Public Health Research Institute, Meibergdreef, Amsterdam, The Netherlands

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Background

Subclinical thyroid diseases are often the subject of debate concerning their clinical significance, the appropriateness of diagnostic testing, and possible treatment. This systematic review addresses the variation in international guidelines for subclinical hyperthyroidism, focusing on diagnostic workup, treatment, and follow-up recommendations.

Methods

Following the PRISMA guidelines, we searched PubMed, Embase, and guideline-specific databases and included clinical practice guidelines with recommendations on subclinical hyperthyroidism. Guideline recommendations were extracted, and quality assessment was performed using selected questions of the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument.

Results

Of the 2624 records screened, 22 guidelines were included, which were published between 2007 and 2021. Guideline quality was generally intermediate to low. Diagnostic approaches differed substantially, particularly in the extent of recommended testing. Treatment initiation depended on TSH levels, age, and comorbidities, but the level of detail regarding defining precise comorbidities varied. Recommendations for monitoring intervals for follow-up ranged from 3 to 12 months.

Conclusion

This review underscores the existing variability in (inter)national guidelines concerning subclinical hyperthyroidism. There isa need for clear recommendations in guidelines considering diagnostic workup, treatment, and follow-up of subclinical hyperthyroidism. In order to establish this, future research should focus on determining clear and evidence-based intervention thresholds.

Open access
Kamilla R Riis Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark
Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

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Steen J Bonnema Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark
Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

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Anja F Dreyer Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark
Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

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Dorte Glintborg Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark

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Niels Bilenberg Department of Child and Adolescent Mental Health, Mental Health Services in the Region of Southern Denmark, University of Southern Denmark Odense, Odense, Denmark

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Dorthe Bleses TrygFonden’s Centre for Child Research and School of Communication and Culture, Aarhus University, Aarhus, Denmark

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Fabio Trecca TrygFonden’s Centre for Child Research and School of Communication and Culture, Aarhus University, Aarhus, Denmark

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Marianne S Andersen Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark
Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

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Objective

Maternal thyroid autoimmunity and thyroid function in early pregnancy may impact fetal neurodevelopment. We aimed to investigate how thyroid autoimmunity and thyroid function in early pregnancy were associated with language acquisition in offspring at 12–36 months of age.

Methods

This study was embedded in the prospective Odense child cohort. Mother–child dyads were excluded in case of maternal intake of thyroid medication during pregnancy. The parents completed MacArthur–Bates Communicative Development Inventories (MB-CDI) every third month to assess their offspring’s productive vocabulary. All completed reports for each child were included in the analyses. Logistic growth curve models evaluated associations between MB-CDI scores and levels of maternal thyroid peroxidase antibodies (TPOAb), free thyroxine (FT4), and thyrotropin, respectively, measured in early pregnancy (median gestational week 12). All models were stratified by offspring sex and adjusted for maternal age, education, pre-pregnancy body mass index, parity, breastfeeding, and offspring age.

Results

The study included 735 mother–child dyads. Children born to mothers with TPOAb ≥11 kIU/L, opposed to TPOAb <11 kIU/L, had a lower probability of producing words at age 18–36 months for girls (OR = 0.78, P < 0.001) and 33–36 months for boys (OR = 0.83, P < 0.001). The probability of producing words was higher in girls at 30–36 months of age with low-normal maternal FT4 vs high-normal FT4 (OR = 0.60, P < 0.001), and a similar trend was seen in boys. Results were ambiguous for thyrotropin.

Conclusion

In women without known thyroid disease, TPOAb positivity in early pregnancy was negatively associated with productive vocabulary acquisition in girls and boys. This association was not mediated by a decreased thyroid function, as low-normal maternal FT4, unexpectedly, indicated better vocabulary acquisition. Our results support that maternal thyroid autoimmunity per se may affect fetal neurodevelopment.

Open access
Valentina Cirello Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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Marina Lugaresi Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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Claudia Moneta Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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Patrice Dufour Department of Clinical, Forensic and Environmental Toxicology, University hospital of Liege (CHU Liège), CHU (B35), Liege, Belgium
Center for Interdisciplinary Research on Medicines (C.I.R.M.), University of Liege (ULiège), CHU (B35), Liege, Belgium

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Alessandro Manzo Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy
Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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Erika Carbone Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Carla Colombo Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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

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Corinne Charlier Department of Clinical, Forensic and Environmental Toxicology, University hospital of Liege (CHU Liège), CHU (B35), Liege, Belgium
Center for Interdisciplinary Research on Medicines (C.I.R.M.), University of Liege (ULiège), CHU (B35), Liege, Belgium

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Catherine Pirard Department of Clinical, Forensic and Environmental Toxicology, University hospital of Liege (CHU Liège), CHU (B35), Liege, Belgium
Center for Interdisciplinary Research on Medicines (C.I.R.M.), University of Liege (ULiège), CHU (B35), Liege, Belgium

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Objective

The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case–control cohort.

Methods

We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4′-DDT and 4,4′-DDE) were measured in the serum by liquid or gas chromatography–mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants’ levels, considered individually or as mixture. BRAF V600E mutation was assessed by standard methods.

Results

The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10–3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41–0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants’ mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180.

Conclusion

Our study suggests, for the first time in a case–control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants’ mixture, likely due to a potential reverse causality.

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Ilaria Muller Department of Clinical Sciences and Community Health, University of Milan, Italy
Endocrinology Unit, Graves’ Orbitopathy Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Sara Maioli Department of Clinical Sciences and Community Health, University of Milan, Italy

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Mirco Armenti Department of Clinical Sciences and Community Health, University of Milan, Italy

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Laura Porcaro Department of Clinical Sciences and Community Health, University of Milan, Italy

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Nicola Currò Endocrinology Unit, Graves’ Orbitopathy Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Ophthalmology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Elisabetta Iofrida Department of Specialistic Surgical Sciences, Otolaryngology and Head and Neck Surgery, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Lorenzo Pignataro Department of Clinical Sciences and Community Health, University of Milan, Italy
Department of Specialistic Surgical Sciences, Otolaryngology and Head and Neck Surgery, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Jacopo Manso Endocrinology Unit, Department of Medicine (DIMED), University of Padova, Padova, Italy

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Caterina Mian Endocrinology Unit, Department of Medicine (DIMED), University of Padova, Padova, Italy

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Jens Geginat Department of Clinical Sciences and Community Health, University of Milan, Italy
National Institute of Molecular Genetics (INGM) “Romeo and Enrica Invernizzi”, Milan, Italy

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Mario Salvi Endocrinology Unit, Graves’ Orbitopathy Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Introduction

Secondary thyroid autoimmunity, especially Graves’ disease (GD), frequently develops in patients with multiple sclerosis (MS) following alemtuzumab treatment (ALTZ; anti-CD52). Thyroid eye disease (TED) can also develop, and rituximab (RTX; anti-CD20) is a suitable treatment.

Case presentation

A 37-year-old woman with MS developed steroid-resistant active moderate-to-severe TED 3 years after ALTZ, that successfully responded to a single 500 mg dose of i.v. RTX. Before RTX peripheral B-cells were low, and were totally depleted immediately after therapy. Follow-up analysis 4 years post ALTZ and 1 year post RTX showed persistent depletion of B cells, and reduction of T regulatory cells in both peripheral blood and thyroid tissue obtained at thyroidectomy.

Conclusion

RTX therapy successfully inactivated TED in a patient with low B-cell count derived from previous ALTZ treatment. B-cell depletion in both thyroid and peripheral blood was still present 1 year after RTX, indicating a likely cumulative effect of both treatments.

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Peter PA Smyth UCD School of Medicine, University College Dublin, Dublin, Ireland

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Colin D O’Dowd Ryan Institute’s Centre for Climate & Air Pollution Studies, School of Physics, University of Galway, Ireland

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Global warming is now universally acknowledged as being responsible for dramatic climate changes with rising sea levels, unprecedented temperatures, resulting fires and threatened widespread species loss. While these effects are extremely damaging, threatening the future of life on our planet, one unexpected and paradoxically beneficial consequence could be a significant contribution to global iodine supply. Climate change and associated global warming are not the primary causes of increased iodine supply, which results from the reaction of ozone (O3) arising from both natural and anthropogenic pollution sources with iodide (I) present in the oceans and in seaweeds (macro- and microalgae) in coastal waters, producing gaseous iodine (I2). The reaction serves as negative feedback, serving a dual purpose, both diminishing ozone pollution in the lower atmosphere and thereby increasing I2. The potential of this I2 to significantly contribute to human iodine intake is examined in the context of I2 released in a seaweed-abundant coastal area. The bioavailability of the generated I2 offers a long-term possibility of increasing global iodine status and thereby promoting thyroidal health. It is hoped that highlighting possible changes in iodine bioavailability might encourage the health community to address this issue.

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