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Liliana Ribeiro Santos Internal Medicine Department, Hospital of Santa Maria, Lisbon, Portugal
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal

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Inês Vasconcelos Bessa Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal
Health Investigation and Innovation Institute (i3S), University of Porto, Porto, Portugal

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Adriana Gaspar da Rocha Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal
Health Investigation and Innovation Institute (i3S), University of Porto, Porto, Portugal
Public Health Unit, ACES Baixo Mondego, Coimbra, Portugal

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Celestino Neves Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal
Department of Endocrinology, Hospital University Centre of São João, Porto, Portugal

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Cláudia Freitas Department of Endocrinology, Hospital University Centre of Porto, Porto, Portugal

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Paula Soares Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal
Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal
Health Investigation and Innovation Institute (i3S), University of Porto, Porto, Portugal
Department of Pathology, Faculty of Medicine of the University of Porto, Porto, Portugal

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Objective

Previous trials show that selenium could be a very useful tool in the control and treatment of autoimmune thyroid diseases. In this cross-sectional study, through a survey, we aim to evaluate Portuguese endocrinologists' perception and pattern of prescription of selenium supplements in these diseases and verify its agreement with current guidelines.

Methods

The endocrinologists registered in the Portuguese Medical Association were sent an email with a web-based questionnaire, regarding their knowledge and use of selenium supplements in thyroid autoimmune pathology.

Results

A total of 105 physicians (33% of the total) submitted the survey. The selenium serum concentration in the general population was unknown to 80% of respondents. Over a third of respondents have never prescribed selenium for autoimmune thyroid disease. However, 89% are not afraid of recommending it, and 61% indicate Graves’ orbitopathy as the pathology they would supplement. In Hashimoto’s thyroiditis, 36% of respondents use selenium occasionally or frequently, and this percentage rises to 60% in Graves’ disease.

Conclusions

Although recommendations only encompass mild Graves’ orbitopathy, selenium is prescribed across the spectrum of autoimmune thyroid diseases, probably due to recent studies that consistently show improvement of biochemical hallmarks in these patients. Further investigation is required on the impact of selenium supplements on primarily clinical outcomes and to identify disorders and/or patients who will benefit the most. Also, there is still insufficient knowledge of this field in the medical community, and evidence-based practice should continue to be promoted by endocrinology societies.

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Juan Ren ENS de Lyon, INRAE, CNRS, Institut de Génomique Fonctionnelle de Lyon, Lyon, France

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Frédéric Flamant ENS de Lyon, INRAE, CNRS, Institut de Génomique Fonctionnelle de Lyon, Lyon, France

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Thyroid hormones are known to trigger metamorphosis in an amphibian. This review discusses the hypothesis according to which they act in a similar manner to synchronize the post-natal development of mice, using brain, brown adipose tissue, and heart as examples.

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Benjamin Chevalier Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France
University of Lille, Lille, France

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Oriane Karleskind Department of Pathology, Lille University Hospital, Lille, France

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Arnaud Jannin Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France
University of Lille, Lille, France

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Olivier Farchi Department of Biochemistry and Molecular Biology, Hormonology Metabolism Nutrition Oncology, Lille University Hospital, Lille, France

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Catherine Vermaut Department of Biochemistry and Molecular Biology, Hormonology Metabolism Nutrition Oncology, Lille University Hospital, Lille, France

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Alexandre Escande Academic Department of Radiation Oncology, Oscar Lambret Comprehensive Cancer Center, Lille, France
CRIStAL UMR CNRS 9189, University of Lille, Villeneuve-d’Ascq, France

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Clio Baillet Department of Nuclear Medicine, Lille University Hospital, Lille, France

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Stéphanie Espiard Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France
University of Lille, Lille, France
Institut National de la Santé et de la Recherche Médicale (INSERM), European Genomic Institute for Diabetes (EGID), CHU Lille, Lille, France

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Marie-Christine Vantyghem Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France
University of Lille, Lille, France
Institut National de la Santé et de la Recherche Médicale (INSERM), European Genomic Institute for Diabetes (EGID), CHU Lille, Lille, France

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Bruno Carnaille University of Lille, Lille, France

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Emmanuelle Leteurtre University of Lille, Lille, France
Department of Pathology, Lille University Hospital, Lille, France
University of Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France

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Christine Do Cao Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France

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Introduction

Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer with a bleak prognosis. Favorable outcomes are rare but help decipher molecular pathophysiology, investigate prognosis factors, and discover new therapeutic targets.

Case presentation

Two patients were diagnosed with locally advanced nonresectable ATC, one with metastatic extension. Each patient received chemotherapy and radiotherapy, allowing thyroid surgical resection. In both cases, the pathological examination was consistent with complete response with no viable tumor cells. After follow-ups of 48 and 70 months, both patients remain disease-free. Molecular explorations on thyroid biopsies revealed microsatellite instability (MSI) and alterations on mismatch repair–gene complex, also PTEN and ATM variants in both cases. Both also presented with non-classical immune infiltrate composed of equal parts T CD4+ lymphocytes and macrophages.

Conclusion

We report two cases of patients cured from advanced ATC and for the first time provide genetic and immunological explorations in this setting. It seems with these two cases that MSI-ATCs may indicate a better prognosis. Our study hypothesizes different responsible mechanisms including increased sensitivity to chemoradiotherapy and/or immune tumor infiltrate modulation.

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

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Joana Simões-Pereira Endocrinology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Sara Donato Endocrinology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
Nova Medical School, Lisbon, Portugal

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Mariana Horta Radiology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon Portugal

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Branca Maria Cavaco Molecular Pathobiology Research Unit (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Miguel Rito Pathology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Pedro Gomes Head and Neck Surgery Department, 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
Nova Medical School, Lisbon, Portugal

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Background

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors. ATC is frequently diagnosed at advanced stages with unresectable disease and palliative care is often indicated. Recently, several patient-tailored therapies for ATC are emerging due to advances in molecular profiling of these tumors. Entrectinib is a potent oral selective inhibitor of neutrotrophic tropomyosin receptor kinase (NTRK), ROS1, and anaplastic lymphoma kinase fusions. The experience regarding ATC and other thyroid carcinomas, particularly in the neoadjuvant setting, is minimal.

Case report

We present a case of a 51-year-old female patient presenting with a bulky mass of the left thyroid lobe measuring 100 × 108 × 80 mm that was considered surgically unresectable. While waiting for next-generation sequence (NGS) profiling, lenvatinib was initiated. There was an initial clinical and imagiologic response; however, progression occurred after 12 weeks, and at this time NGS identified an ETV6-NTRK3 fusion and entrectinib was started. After 12 weeks, tumor diameters reduced to a minimum of 68×60×49 mm, and the patient underwent total thyroidectomy plus central lymphadenectomy. Histological diagnosis confirmed an ATC (pT4a R2 N1a). Adjuvant radiotherapy (RT) (60 Grays) with weekly paclitaxel (45 mg/m2) was then administered followed by maintenance entrectinib 600 mg daily. Fluorodeoxyglucose positron emission tomography performed 3 months after completion of RT showed only non-specific uptake in the posterior wall of the hypopharynx and larynx, suggestive of inflammation.

Conclusion

We report the first case of an ATC with a dramatic response to neoadjuvant therapy with entrectinib, which enabled surgical resection of an ab initio unresectable tumor.

Open access
Eduardo Crespo Vallejo Interventional Radiology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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Antonio Hermosin Interventional Radiology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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Manuel Gargallo Endocrinology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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Álvaro Villalba Interventional Radiology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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Eduardo Daguer Interventional Radiology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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José Flores Interventional Radiology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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Javier Periañez Interventional Radiology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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Joaquim Amorín Interventional Radiology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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Ernesto Santos Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

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Objective

This study aimed to evaluate the safety and long-term efficacy using the multiple overlapping ablation technique with a novel non-cooled microwave system in benign symptomatic thyroid nodules.

Methods

This prospective cohort single-center study collected complication data from the start of the procedure to 30 days postoperatively and evaluated the safety and effectiveness with a follow-up of 24 months. Ultrasound examinations were performed to determine the volume shrinkage during follow-up. Thyroid function cosmetic and symptoms scores and satisfaction degree were evaluated.

Results

A total of 30 symptomatic benign thyroid nodules were treated by microwave ablation using a power between 15 and 30 W depending on the size of the nodule to be treated. The volume reduction rates in months 1, 3, 6, 9, 12, and 24 after ablation were 32, 59, 67, 69, 73, and 81%, respectively. The mean symptom score and mean cosmetic score before treatment were 4 and 3, respectively, while after treatment they dropped to 3 and 1, respectively. Thyroid function indicators fluctuated in the normal range and those with hyperthyroidism recovered to normal parameters. One case of temporary laryngeal paralysis occurred postoperatively and fully recovered in less than 3 months.

Conclusions

The novel microwave ablation system presented herein can help achieve good clinical success rate in benign thyroid nodules with a satisfying safety profile. The microwave ablation performed with the multiple overlapping ablation technique could be a good alternative to surgery and radiofrequency ablation in the management of benign thyroid nodules.

Open access
Simona Censi Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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

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Teresa Benvenuti Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Ilaria Piva Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Maurizio Iacobone Endocrine Surgery Unit, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy

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Alberto Mondin Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Francesca Torresan Endocrine Surgery Unit, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy

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Daniela Basso Laboratory Medicine, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Gino Crivellari Hereditary Tumor Unit, Istituto Oncologico Veneto, IOV - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padova, Italy

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Stefania Zovato Hereditary Tumor Unit, Istituto Oncologico Veneto, IOV - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padova, Italy

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

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Objective

Calcitonin (Ct) represents the most important biochemical marker of medullary thyroid cancer (MTC), but has certain limits. We analyzed the performance of procalcitonin (ProCt) in follow-up MTC patients.

Methods

In this monocentric and retrospective study, we consecutively obtained ProCt and Ct values from all MTC patients that we visited during the period from April 2021 to May 2022. Patients were defined as having structural evidence of disease (29/90, 32.2%) irrespective of Ct values or, in its absence, as not evident disease (NED) if Ct was ≤10 ng/L (47/90, 52.2%), or minimal residual disease if Ct was >10 ng/L (14/90, 15.6%).

Results

Ct and ProCt values were highly correlated (r = 0.883, P < 0.01). Median ProCt values differed between NED, minimal residual disease, and structural disease, being 0.04 ng/mL, 0.26 ng/mL, and 1.98 ng/mL, respectively (P < 0.01). ProCt was undetectable (<0.04 ng/mL) in 40/47 (85.1%) of NED patients, in 3/14 (21.4%) patients with minimal residual disease and in none of the patients with a structural disease (P < 0.01). Among the 11 patients with detectable but ≤10 ng/L Ct and undetectable ProCt values, none had a structural disease. The most accurate cut-off of ProCt to distinguish between the presence or absence of a structural disease was >0.12 ng/mL (P < 0.01, area under the curve: 0.963), with the following sensitivity, specificity, positive predictive value, and negative predictive value (NPV): 100%, 83.61%, 74.4%, and 100.0%.

Conclusions

ProCt and Ct have a high correlation in MTC follow-up. ProCt may be useful as an adjunct to Ct, especially for its NPV concerning the structural disease.

Open access
Tomohiro Kikuchi Department of Computational Diagnostic Radiology and Preventive Medicine, the University of Tokyo Hospital, Hongo, Bunkyo–ku, Tokyo, Japan
Department of Radiology, Jichi Medical University, School of Medicine, Shimotsuke, Tochigi, Japan

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Shouhei Hanaoka Department of Radiology, The University of Tokyo Hospital, Hongo, Bunkyo–ku, Tokyo, Japan

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Takahiro Nakao Department of Computational Diagnostic Radiology and Preventive Medicine, the University of Tokyo Hospital, Hongo, Bunkyo–ku, Tokyo, Japan

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Yukihiro Nomura Department of Computational Diagnostic Radiology and Preventive Medicine, the University of Tokyo Hospital, Hongo, Bunkyo–ku, Tokyo, Japan
Center for Frontier Medical Engineering, Chiba University, Yayoicho, Inage–ku, Chiba, Japan

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Takeharu Yoshikawa Department of Computational Diagnostic Radiology and Preventive Medicine, the University of Tokyo Hospital, Hongo, Bunkyo–ku, Tokyo, Japan

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Ashraful Alam Department of Computational Diagnostic Radiology and Preventive Medicine, the University of Tokyo Hospital, Hongo, Bunkyo–ku, Tokyo, Japan

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Harushi Mori Department of Radiology, Jichi Medical University, School of Medicine, Shimotsuke, Tochigi, Japan

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Naoto Hayashi Department of Computational Diagnostic Radiology and Preventive Medicine, the University of Tokyo Hospital, Hongo, Bunkyo–ku, Tokyo, Japan

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Objective

This study aimed to determine a standardized cut-off value for abnormal 18F-fluorodeoxyglucose (FDG) accumulation in the thyroid gland.

Methods

Herein, 7013 FDG–PET/CT scans were included. An automatic thyroid segmentation method using two U-nets (2D- and 3D-U-net) was constructed; mean FDG standardized uptake value (SUV), CT value, and volume of the thyroid gland were obtained from each participant. The values were categorized by thyroid function into three groups based on serum thyroid-stimulating hormone levels. Thyroid function and mean SUV with increments of 1 were analyzed, and risk for thyroid dysfunction was calculated. Thyroid dysfunction detection ability was examined using a machine learning method (LightGBM, Microsoft) with age, sex, height, weight, CT value, volume, and mean SUV as explanatory variables.

Results

Mean SUV was significantly higher in females with hypothyroidism. Almost 98.9% of participants in the normal group had mean SUV < 2 and 93.8% participants with mean SUV < 2 had normal thyroid function. The hypothyroidism group had more cases with mean SUV ≥ 2. The relative risk of having abnormal thyroid function was 4.6 with mean SUV ≥ 2. The sensitivity and specificity for detecting thyroid dysfunction using LightGBM (Microsoft) were 14.5 and 99%, respectively.

Conclusions

Mean SUV ≥ 2 was strongly associated with abnormal thyroid function in this large cohort, indicating that mean SUV with FDG–PET/CT can be used as a criterion for thyroid evaluation. Preliminarily, this study shows the potential utility of detecting thyroid dysfunction based on imaging findings.

Open access
Chantal A Lebbink Wilhelmina Children’s Hospital and Princess Máxima Center, Utrecht, The Netherlands

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Thera P Links Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

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Agnieszka Czarniecka The Oncologic and Reconstructive Surgery Clinic, M. Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland

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Renuka P Dias Department of Paediatric Endocrinology and Diabetes, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, United Kingdom

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

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Louise Izatt Department of Clinical Genetics, Guy's and St Thomas’ NHS Foundation Trust, London, United Kingdom

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Heiko Krude Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin, Berlin, Germany

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Kerstin Lorenz Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany

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Markus Luster Department of Nuclear Medicine, University Hospital Marburg, Marburg, Germany

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Kate Newbold Thyroid Therapy Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom

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Arnoldo Piccardo Department of Nuclear Medicine, EO Ospedali Galliera, Genoa, Italy

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

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Toru Takano Thyroid Center, Rinku General Medical Center, Osaka, Japan

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A S Paul van Trotsenburg Department of Pediatric Endocrinology, Emma Children's Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands

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Frederik A Verburg Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

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Hanneke M van Santen Wilhelmina Children’s Hospital and Princess Máxima Center, Utrecht, The Netherlands

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At present, no European recommendations for the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC) exist. Differences in clinical, molecular, and pathological characteristics between pediatric and adult DTC emphasize the need for specific recommendations for the pediatric population. An expert panel was instituted by the executive committee of the European Thyroid Association including an international community of experts from a variety of disciplines including pediatric and adult endocrinology, pathology, endocrine surgery, nuclear medicine, clinical genetics, and oncology. The 2015 American Thyroid Association Pediatric Guideline was used as framework for the present guideline. Areas of discordance were identified, and clinical questions were formulated. The expert panel members discussed the evidence and formulated recommendations based on the latest evidence and expert opinion. Children with a thyroid nodule or DTC require expert care in an experienced center. The present guideline provides guidance for healthcare professionals to make well-considered decisions together with patients and parents regarding diagnosis, treatment, and follow-up of pediatric thyroid nodules and DTC.

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Joke Marlier Department of Endocrinology, Ghent University Hospital, Ghent, Belgium

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Guy T’Sjoen Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
Department of Internal Medicine & Pediatrics, Ghent University, Ghent, Belgium

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Jean Kaufman Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
Department of Internal Medicine & Pediatrics, Ghent University, Ghent, Belgium

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Bruno Lapauw Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
Department of Internal Medicine & Pediatrics, Ghent University, Ghent, Belgium

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Introduction

Thyroid hormone replacement in central hypothyroidism (CHT) is more difficult than in primary hypothyroidism (PHT), putting patients at risk for inappropriate substitution. In this study, we compared the dosage of thyroid hormone replacement in patients with CHT with that of patients with PHT. In addition, we explored and compared quality of life (QoL) between both groups, based on two questionnaires, the SF-36 health score and the thyroid-specific ThyPRO score.

Methods

This is a monocentric, cross-sectional study, performed at the Ghent University Hospital (Belgium). We included 82 patients in total, 41 patients with CHT and 41 patients with PHT. At the time of inclusion, all patients had to have a stable dose of levothyroxine over the past 6 months and patients with PHT needed to be euthyroid (defined as having a thyroid-stimulating hormone level within the reference range, 0.2–4.5 mU/L). All data were retrieved from medical files, and questionnaires on QoL were self-administered.

Results

The CHT and PHT groups were comparable regarding age and BMI. There was no significant difference between both groups regarding total daily dose of levothyroxine (100 (93.75–125.00) vs 107.14 (75.00–133.93) μg in CHT and PHT, respectively; P = 0.87) or daily dose of levothyroxine per kg body weight (1.34 (1.16–1.55) vs 1.55 (1.16–1.82) μg/kg, respectively; P = 0.13). Serum levels of fT4 (P = 0.20) and fT3 (P = 0.10) also did not differ between the two groups and both were in the normal (mid)range for the two groups. Regarding QoL, patients with CHT scored worse in terms of depressive and emotional symptoms, impaired daily and social life.

Conclusion

We could demonstrate a difference in QoL between patients with CHT and PHT. Although patients with CHT had a somewhat lower levothyroxine substitution dose than patients with PHT, this difference was also not significant and probably does not explain the difference in QoL.

Open access