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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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Luigino Dal Maso Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy

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Daniela Pierannunzio National Centre for Disease Prevention and Health Promotion, National Institute of Health, Rome, Italy

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Silvia Francisci National Centre for Disease Prevention and Health Promotion, National Institute of Health, Rome, Italy

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Angela De Paoli Epidemiological Department, Azienda Zero, Padova, Italy

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Federica Toffolutti Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy

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Salvatore Vaccarella Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France

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Silvia Franceschi Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy

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Rossella Elisei Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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Ugo Fedeli Epidemiological Department, Azienda Zero, Padova, Italy

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of the DEPTH Working Group
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of the DEPTH Working Group

Objective

A decrease in the use of radioactive iodine (RAI) treatment for thyroid cancer has been described in the last decade in the US following subsequent updates of the American Thyroid Association guidelines. By contrast, population-based data from European countries are lacking. The study aims to assess the frequency and long-term trends in the use of RAI in Italy.

Methods

From the Italian national hospital discharge database, the proportion of RAI treatment after total thyroidectomy with thyroid cancer diagnosis has been assessed by sex and age class during 2001–2018.

Results

Throughout the whole study period, RAI was performed after 58% of 149,419 total thyroidectomies. The use of RAI was higher for men and younger patients; it peaked in 2007 (64% in women and 68% in men) and declined thereafter (2018: 46% in women and 53% in men), with a similar pattern observed across all ages and areas.

Conclusion

National data show that in Italy trends in RAI treatment paraleled those observed in the US. Further monitoring of the use of RAI is warranted in Italy, as elsewhere, to assess the impact of international guidelines on real-life clinical management of thyroid cancer.

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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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Daniele Ceruti Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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Simone De Leo Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano, IRCCS, Milan, Italy

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Grzegorz Bilo Department of Cardiology, San Luca Hospital, Istituto Auxologico Italiano, IRCCS, Milan, Italy
Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

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Matteo Trevisan Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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Noemi Giancola Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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Claudia Moneta Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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Gianfranco Parati Department of Cardiology, San Luca Hospital, Istituto Auxologico Italiano, IRCCS, Milan, Italy
Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

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Luca Persani 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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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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Background

Hypertension (HTN) is the most frequent adverse event during treatment with lenvatinib (LEN), but data on its best management are limited.

Aim

The objective of this study was to assess incidence, features and best management of LEN-related HTN in a consecutive single tertiary-care centre cohort.

Methods

Twenty-nine patients were followed up for a mean time of 29.8 months (6–77 months).

Results

After a mean follow-up of 6.8 months, HTN was recorded in 76% of cases, as a de novo occurrence in half of them. HTN significantly correlated with LEN dose and was of grade 1, grade 2 and grade 3 in 5%, 50% and 45% of patients, respectively. The majority (77%) of patients with HTN developed proteinuria. There was no correlation between HTN and proteinuria or clinical features or best morphological response or any other adverse event (AE), with the exception of diarrhoea. Patients with or without pre-existing HTN or any other cardiovascular disease had a similar incidence of HTN during LEN, thus excluding the impact of this potential predisposing factor. After evaluation by a dedicated cardiologist, medical treatment was introduced in 21/22 patients (polytherapy in 20 of them). The most frequently used drugs were calcium channel blockers (CCBs) due to their effect on vasodilation. In case of poor control, CCBs were associated with one or more anti-hypertensive drug.

Conclusion

HTN is a frequent and early AE in patients on LEN treatment. We suggest a diagnostic and therapeutic algorithm to be applied in clinical practice to allow efficient HTN control and improve patient compliance, reducing LEN discontinuation.

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Santiago Tofé Department of Endocrinology, University Hospital Son Espases, Palma de Mallorca, Spain

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Iñaki Argüelles Department of Endocrinology, University Hospital Son Espases, Palma de Mallorca, Spain

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Ana Forteza Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain

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Cristina Álvarez Department of Surgery, Section of Endocrine Surgery, University Hospital Son Espases, Palma de Mallorca, Spain

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Alessandra Repetto Department of Nuclear Medicine, University Hospital Son Espases, Palma de Mallorca, Spain

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Luis Masmiquel Department of Endocrinology, University Hospital Son Llatzer, Palma de Mallorca, Spain

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Irene Rodríguez Department of Endocrinology, University Hospital Son Llatzer, Palma de Mallorca, Spain

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Eladio Losada Department of Endocrinology, Hospital Can Misses, Ibiza, Spain

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Nuria Sukunza Department of Endocrinology, Hospital de Manacor, Manacor, Spain

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María Cabrer Department of Endocrinology, Hospital Comarcal de Inca, Inca, Spain

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Mildred Sifontes Department of Pathology, Hospital Mateu Orfila, Menorca, Spain

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María del Mar del Barrio Department of Pathology, Hospital Mateu Orfila, Menorca, Spain

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Antonia Barceló Department of Laboratory, University Hospital Son Espases, Palma de Mallorca, Spain

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Álvaro Tofé Department of Maxillofacial Surgery, Hospital Puerta del Mar, Cádiz, Spain

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Vicente Pereg Department of Endocrinology, University Hospital Son Espases, Palma de Mallorca, Spain

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Objective

Global thyroid cancer (TC) incidence is growing worldwide, but great heterogenicity exists among published studies, and thus, population-specific epidemiological studies are needed to adequate health resources and evaluate the impact of overdiagnosis.

Methods

We conducted a Public Health System database retrospective review of TC incident cases from 2000 to 2020 in the Balearic Islands region and evaluated age-standardized incidence rate (ASIR), age at diagnosis, gender distribution, tumor size and histological subtype, mortality rate (MR), and cause of death. Estimated annual percent changes (EAPCs) were also evaluated and data from the 2000–2009 period were compared to the 2010–2020 period when neck ultrasound (US) was routinely performed by clinicians at Endocrinology Departments.

Results

A total of 1387 incident cases of TC were detected. Overall, ASIR (×105) was 5.01 with a 7.82% increment in EAPC. A significant increase in the 2010–2020 period was seen for ASIR (6.99 vs 2.82, P < 0.001) and age at diagnosis (52.11 vs 47.32, P < 0.001) compared to the 2000–2009 period. A reduction in tumor size (2.00 vs 2.78 cm, P < 0.001) and a 6.31% increase in micropapillary TC (P < 0.05) were also seen. Disease-specific MR remained stable at 0.21 (×105). The mean age at diagnosis for all mortality groups was older than survivors (P < 0.001).

Conclusion

The incidence of TC has grown in the 2000–2020 period in the Balearic Islands, but MR has not changed. Beyond other factors, a significant contribution of overdiagnosis to this increased incidence is likely due to changes in the routine management of thyroid nodular disease and increased availability of neck US.

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Sepehr Torabinejad Department of Clinical Medicine and Surgery, University of Naples ’Federico II’, Naples, Italy

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Caterina Miro Department of Clinical Medicine and Surgery, University of Naples ’Federico II’, Naples, Italy

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Biagio Barone Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II

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Ciro Imbimbo Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II

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Felice Crocetto Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II

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Monica Dentice Department of Clinical Medicine and Surgery, University of Naples ’Federico II’, Naples, Italy
CEINGE – Biotecnologie Avanzate Scarl, Naples, Italy

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There is increasing evidence that thyroid hormones (THs) work in an integrative fashion with androgen receptors (ARs) to regulate gonadal differentiation and reproductive function. Studies reveal that THs have interactions with the AR promoter region and increase AR expression. THs also have a role in the regulation of enzymes involved in the biosynthesis of androgens, such as 5α-reductase, which is essential in the conversion of testosterone into its active form, 5α-dihydrotestosterone. Additionally, the presence of androgen response elements in the promoter regions of TH-related genes, such as deiodinases and TH receptor isoforms, has been identified in some vertebrates, indicating a mutual interaction between THs and ARs. Since the androgen signaling pathway, mediated by ARs, plays a key role in the formation and progression of prostate cancer (PCa), the existence of crosstalk between THs and ARs supports the epidemiologic and experimental evidence indicating a relationship between the high incidence of PCa and hyperthyroidism. This article aims to review the role of androgen-TH crosstalk in PCa and its implication in clinical management. As life expectancy is growing these days, it can increase the number of patients with PCa and the critical relevance of the disease. In order to gain better knowledge about PCa and to improve clinical management, it is essential to get better insight into the key factors related to the formation and progression of this cancer.

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Cengiz Kara Department of Molecular Medicine, Institute of Graduate Studies, Ondokuz Mayis University, Samsun, Turkey
Department of Pediatric Endocrinology, Faculty of Medicine, Istinye University, Istanbul, Turkey

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Jamala Mammadova Pediatric Endocrinology Unit, Altinbas University Medicalpark Bahçelievler Hospital, Istanbul, Turkey

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Ümmet Abur Department of Molecular Medicine, Institute of Graduate Studies, Ondokuz Mayis University, Samsun, Turkey
Department of Medical Genetics, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey

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Cagri Gumuskaptan Department of Molecular Medicine, Institute of Graduate Studies, Ondokuz Mayis University, Samsun, Turkey
Department of Medical Genetics, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey

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Elif İzci Güllü Department of Pediatric Endocrinology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey

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Ayhan Dağdemir Department of Molecular Medicine, Institute of Graduate Studies, Ondokuz Mayis University, Samsun, Turkey

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Murat Aydın Department of Pediatric Endocrinology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey

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Objective

Guidelines on congenital hypothyroidism (CH) recommend that genetic testing should aim to improve diagnosis, treatment or prognosis, but it is unclear which patients would benefit most from the genetic investigation. We aimed to investigate the genetic etiology of transient CH (TCH) and permanent CH (PCH) in a well-characterized cohort, and thereby evaluate the impact of genetic testing on the management and prognosis of children with CH.

Methods

A total of 48 CH patients with normal, goitrous (n 5) or hypoplastic thyroid (n 5) were studied by high-throughput sequencing using a custom-designed 23-gene panel. Patients initially categorized as TCH (n 15), PCH (n 26) and persistent hyperthyrotropinemia (PHT, n 7) were re-evaluated after genetic testing.

Results

Re-evaluation based on genetic testing changed the initial diagnoses from PCH to PHT (n 2) or TCH (n 3) and from PHT to TCH (n 5), which resulted in a final distribution of TCH (n 23), PCH (n 21) and PHT (n 4). Genetic analysis also allowed us to discontinue treatment in five patients with monoallelic TSHR or DUOX2, or no pathogenic variants. The main reasons for changes in diagnosis and treatment were the detection of monoallelic TSHR variants and the misdiagnosis of thyroid hypoplasia on neonatal ultrasound in low birthweight infants. A total of 41 (35 different, 15 novel) variants were detected in 65% (n 31) of the cohort. These variants, which most frequently affected TG, TSHR and DUOX2, explained the genetic etiology in 46% (n 22) of the patients. The molecular diagnosis rate was significantly higher in patients with PCH (57%, n 12) than TCH (26%, n 6).

Conclusions

Genetic testing can change diagnosis and treatment decisions in a small proportion of children with CH, but the resulting benefit may outweigh the burden of lifelong follow-up and treatment.

Open access
Daniela Dias Endocrinology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Inês Damásio Endocrinology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Pedro Marques Endocrinology Department, Hospital de Santa Maria, Centro Hospitalar Universitário de Lisboa Norte (CHULN), Lisbon, Portugal

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Helder Simões Endocrinology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Ricardo Rodrigues Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Branca Maria Cavaco Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Valeriano Leite Endocrinology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
Nova Medical School: Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Lisbon, Portugal

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Background

Treatment of advanced follicular thyroid carcinoma (FTC) is based primarily on indirect evidence obtained with multikinase inhibitors (MKI) in clinical trials in which papillary carcinomas represent the vast majority of cases. However, it should be noted that MKI have a non-negligible toxicity that may decrease the patient’s quality of life. Conventional chemotherapy with GEMOX (gemcitabine plus oxaliplatin) is an off-label therapy, which seems to have some effectiveness in advanced differentiated thyroid carcinomas, with a good safety profile, although further studies are needed.

Case report

We report a case of a metastatic FTC, resistant to several lines of therapy. However, with a durable response to GEMOX, the overall survival of our patient appears to have been extended significantly due to this chemotherapy.

Conclusion

GEMOX may have a role in patients with thyroid cancer unresponsive to MKI.

Open access
Agneta Lindo Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden
Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
The National Task Force in Hyperthyroidism, Swedish National System for Knowledge-Driven Management, Umeå, Sweden

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Anne Breikert The National Task Force in Hyperthyroidism, Swedish National System for Knowledge-Driven Management, Umeå, Sweden
Department of Endocrinology and Diabetes, Örebro University Hospital, Örebro, Sweden

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Peter Lakwijk The National Task Force in Hyperthyroidism, Swedish National System for Knowledge-Driven Management, Umeå, Sweden
Thyroid Federation International, Kungsbacka, Sweden

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Christin Lundberg The National Task Force in Hyperthyroidism, Swedish National System for Knowledge-Driven Management, Umeå, Sweden
Swedish Thyroid Association, Stockholm, Sweden

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Katarina Lunner The National Task Force in Hyperthyroidism, Swedish National System for Knowledge-Driven Management, Umeå, Sweden
Swedish Thyroid Association, Stockholm, Sweden

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Birgitta Johansson Institute of Neuroscience and Physiology Department of Clinical Neuroscience, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden

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Helena Filipsson Nyström Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden
Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
The National Task Force in Hyperthyroidism, Swedish National System for Knowledge-Driven Management, Umeå, Sweden
Sweden and Wallenberg Center for Molecular and Translational Medicine, Västra Götaland Region, Göteborg, Sweden

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Patients with Graves' disease (GD) not only need appropriate medical care, but they also need to be cared for. The aim of this review is to examine the literature on GD patient needs, expectations, perceptions, and quality of life. We will also present methods for patient care, define gaps in knowledge, and suggest factors that can be introduced into the regular care of GD patients. Patient information, teamwork with thyroid/contact nurses, education of personnel and patients, quality of life measurements, and the formation of a rehabilitation program have enough evidence to be implemented into regular care. However, visualizing patient needs through person-centered care requires further evaluation in GD patients before being implemented in routine care. We conclude that considerable improvement in nursing can be achieved in relation to GD.

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Yiyun Cui Department of Endocrinology, Children's Hospital of Nanjing Medical University, Nanjing, China

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Jinlong Chen Department of Cardiology, Children's Hospital of Nanjing Medical University, Nanjing, China

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Rui Guo Department of Endocrinology, Children's Hospital of Nanjing Medical University, Nanjing, China

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Ruize Yang Department of Public Health, Children's Hospital of Nanjing Medical University, Nanjing, China

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Dandan Chen Department of Endocrinology, Children's Hospital of Nanjing Medical University, Nanjing, China

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Wei Gu Department of Endocrinology, Children's Hospital of Nanjing Medical University, Nanjing, China

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Francis Manyori Bigambo School of Public Health, Nanjing Medical University, Nanjing, China

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Xu Wang Department of Endocrinology, Children's Hospital of Nanjing Medical University, Nanjing, China

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Background

Graves' disease (GD) among children has attracted wide attention. However, data on long-term follow-up are scarce, especially in China. This study aimed to investigate the prognosis after regular treatments of GD and to identify possible influencing factors.

Methods

A total of 204 newly diagnosed GD children in the Children's Hospital of Nanjing Medical University between 2013 and 2019 were included in this study. The cases involved were divided into remission group, relapse group, and continuing treatment group according to therapy outcomes. Relationships between prognosis and possible influencing factors in remission and relapse groups were analyzed.

Results

All 204 cases were treated with methimazole at presentation with GD. Due to severe complications, 4 (2.0%) cases changed medication to propylthiouracil. Of all the GD children included, 79 (38.7%) had remission, and 40 (50.6%) relapsed after remission. For each additional month before free thyroxine fell into the reference range with treatment, the risk of relapse increased 1.510 times (adjusted odds ratio (OR)=2.510, 95%CI: 1.561–4.034) compared to those in the remission group. On the contrary, the risk of relapse was reduced by 0.548 times for each additional hour of sleep duration per day (adjusted OR=0.452, 95%CI: 0.232–0.879).

Conclusion

GD children have a high relapse rate after remission, and most of them occur within 1 year. Thyroid function should be reexamined regularly after drug withdrawal. The response to medication and lifestyle of GD children may affect the prognosis.

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Eveline Bruinstroop Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands

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Anne H van der Spek Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands

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

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Thyroid hormones play an essential role in regulating whole-body homeostasis. Deiodinases are known to convert thyroid hormone from the prohormone thyroxine (T4) to the bioactive hormone tri-iodothyronine (T3) and convert both T4 and T3 toward their inactive metabolites 3,3’,5’-tri-iodothyronine (rT3) and 3,3’-di-iodothyronine (3,3’-T2). Deiodinases are thus important for the regulation of intracellular thyroid hormone concentrations. This is known to be crucial both during development and adult life in regulating thyroid hormone-related gene transcription. This review discusses the importance of liver deiodinases in determining serum and liver thyroid hormone concentrations, liver metabolism and liver disease.

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