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  • Author: Celestino Neves x
  • Hyperthyroidism and thyrotoxicosis x
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Marta Nascimento Soares Faculty of Medicine of the University of Porto, Porto, Portugal

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Marta Borges-Canha Faculty of Medicine of the University of Porto, Porto, Portugal
Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal
Department of Surgery and Physiology, Cardiovascular Research Unit, Faculty of Medicine from the University of Porto, Porto, Portugal

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Celestino Neves Faculty of Medicine of the University of Porto, Porto, Portugal
Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal
Institute for Research Innovation in Health, University of Porto, Porto, Portugal

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João Sérgio Neves Faculty of Medicine of the University of Porto, Porto, Portugal
Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal
Department of Surgery and Physiology, Cardiovascular Research Unit, Faculty of Medicine from the University of Porto, Porto, Portugal

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Davide Carvalho Faculty of Medicine of the University of Porto, Porto, Portugal
Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal
Institute for Research Innovation in Health, University of Porto, Porto, Portugal

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Aim

The prevalence of thyroid nodules and the risk of thyroid cancer in patients with Graves’ disease is uncertain. We aimed to evaluate the prevalence of thyroid nodules and cancer in patients with Graves’ disease.

Methods

Retrospective observational study of adult subjects with Graves' disease (positive autoantibodies thyrotropin receptor antibodies (TRAbs)) between 2017 and 2021 at our center was done. We evaluated the prevalence of thyroid nodules and cancer in this population and characterized the predictive factors for thyroid malignancy using linear and logistic regression models.

Results

We evaluated a total of 539 patients with Graves' disease during a median follow-up of 3.3 years (25th–75th percentiles 1.5–5.2 years). Fifty-three percent had thyroid nodules and 18 (3.3%) were diagnosed with thyroid cancer (12 papillary microcarcinomas). All tumors were classified using TNM classification as T1, and only one had lymph node metastasis; there were no recordings of distant metastasis. Sex, age, body mass index, smoking, TSH, and TRAbs levels were not significantly different between patients with and without thyroid cancer. Patients with multiple nodules on ultrasound (OR 1.61, 95%CI 1.04–2.49) and with larger nodules (OR 2.96, 95%CI 1.08–8.14, for 10 mm increase in size) had a greater risk of thyroid cancer diagnosis.

Conclusion

Patients with Graves’ disease had a high prevalence of thyroid nodules and their nodules had a significant risk of thyroid cancer. The risk was higher in those with multiple and larger nodules. Most had low-grade papillary thyroid cancer. More studies are needed to clarify the clinical relevance of these findings.

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Sofia Macedo Institute for Research & Innovation in Health, University of Porto, Porto, Portugal
Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
Faculty of Medicine, University of Porto, Porto, Portugal

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Ana Pestana Institute for Research & Innovation in Health, University of Porto, Porto, Portugal
Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
Faculty of Medicine, University of Porto, Porto, Portugal

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Liliana Santos Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
Faculty of Medicine, University of Porto, Porto, Portugal
North Lisbon University Hospital Center, Lisbon, Portugal

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Celestino Neves Faculty of Medicine, University of Porto, Porto, Portugal
University Hospital Center of São João, Porto, Portugal

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Susana Guimarães Faculty of Medicine, University of Porto, Porto, Portugal
University Hospital Center of São João, Porto, Portugal

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Amaro Duarte-Neto Department of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil

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Marisa Dolhnikoff Department of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil

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Paulo Saldiva Department of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil

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Georgina Alves Institute for Research & Innovation in Health, University of Porto, Porto, Portugal

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Rute Oliveira Institute for Research & Innovation in Health, University of Porto, Porto, Portugal

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Didier Cabanes Institute for Research & Innovation in Health, University of Porto, Porto, Portugal

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Fátima Carneiro Institute for Research & Innovation in Health, University of Porto, Porto, Portugal
Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
Faculty of Medicine, University of Porto, Porto, Portugal
University Hospital Center of São João, Porto, Portugal

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Manuel Sobrinho-Simões Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
Faculty of Medicine, University of Porto, Porto, Portugal
University Hospital Center of São João, Porto, Portugal

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Paula Soares Institute for Research & Innovation in Health, University of Porto, Porto, Portugal
Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
Faculty of Medicine, University of Porto, Porto, Portugal

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Objective

To understand whether thyroid cells can be directly infected by the SARS-CoV-2 virus and to establish a putative correlation with the expression of the host entry machinery: ACE-2, TMPRSS2, and furin.

Methods

We assessed the presence of SARS-CoV-2 virus at the gene level by RT-PCR, viral RNA transcripts localization by in situ hybridization, and by detecting viral proteins by immunohistochemistry for the nucleocapsid and the spike proteins. Furthermore, we also described the immunoexpression of key host factors for virus entry in the COVID-19 thyroid samples.

Results

We performed RT-PCR for SARS-CoV-2 in all autopsy specimens and detected viral genome positivity in 13 of 15 thyroid tissues and in a lung specimen. In 9 of the 14 positive samples, we were also able to confirm SARS-CoV-2 signal by in situ hybridization. Immunohistochemistry for the viral nucleocapsid and spike protein was also positive for ten and nine of the RT-PCR-positive cases, respectively, but revealed a lower sensitivity. We also described, for the first time in a COVID-19 series, the immunohistochemical expression of ACE-2, TMPRSS2, and furin in the thyroid.

Conclusions

Our results obtained in thyroid specimens from deceased COVID-19 patients indicate that thyrocytes can be directly infected by SARS-CoV-2 since we detected the presence of SARS-CoV-2 genome in follicular cells. Nevertheless, we did not find a clear correlation between the presence of viral genome and the expression of the host factors for virus entry, namely ACE-2, TMPRSS2, and furin.

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