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Megumi Fujikawa M Fujikawa, Fujikawa-Megumi Clinic, Fukuoka, Japan

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Ken Okamura K Okamura, Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan

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Objective: As thionamide is associated with various adverse effects, we reevaluated the practical efficacy of potassium iodide (KI) therapy for Graves’ hyperthyroidism (GD).

Methods: We administered KI (mainly 100 mg/day) to 324 untreated GD patients, and added methimazole (MMI) only to those remaining thyrotoxic even at 200 mg/day. When the patient became hypothyroid, MMI if taken was stopped, then levothyroxine (LT4) was added without reducing the KI dose. Radioactive iodine (RI) therapy or thyroidectomy was performed whenever required. We evaluated the early effects of KI at 2-4 weeks, and followed patients for 2 years.

Results: At 2 weeks, serum thyroid hormone decreased in all 324 patients. At 4 weeks, fT4, fT3, and both fT4 and fT3 levels became normal or low in 74.7%, 50.6%, and 50.6%, respectively. In a cross-sectional survey over 2-years, GD was well-controlled with KI or KI+LT4 (KI-effective) in >50% of patients at all time points. Among 288 patients followed for 2 years, 42.7% remained ‘KI-effective’ throughout 2 years (KI Group), 30.9% were well-controlled with additional MMI given for 1-24 months, and 26.4% were successfully treated with ablative therapy (mainly RI). Among ‘KI-effective’ patients at 4 weeks, 76.5% were classified into KI Group. No patients experienced adverse effects of KI.

Conclusion: KI therapy was useful in the treatment of GD. A sufficient dose of KI was effective in >50% of GD patients from 4 weeks to 2 years, and 42.7% (76.5% of ‘KI effective’ patients at 4 weeks) remained ‘KI-effective’ throughout 2 years.

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

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Patrice Rodien Service d’Endocrinologie-Diabétologie-Nutrition, Centre de référence des maladies rares de la Thyroïde et des récepteurs hormonaux, CHU d’Angers, Angers, France.

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Carla Moran Institute of Metabolic Science, University of Cambridge, Cambridge, UK
Endocrine Section, Beacon Hospital, Dublin, Ireland.
School of Medicine, University College Dublin, Ireland
Endocrinology Department, St Vincent’s University Hospital, Dublin, Ireland

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W Edward Visser Department of Internal Medicine and Rotterdam Thyroid Center, Erasmus University Medical Center, Rotterdam, The Netherlands

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Stefan Groeneweg Department of Internal Medicine and Rotterdam Thyroid Center, Erasmus University Medical Center, Rotterdam, The Netherlands

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Robin Peeters Department of Internal Medicine and Rotterdam Thyroid Center, Erasmus University Medical Center, Rotterdam, The Netherlands

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Samuel Refetoff Departments of Medicine and Paediatrics and Committee on Genetics, The University of Chicago, Chicago, Illinois, USA

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Mark Gurnell Institute of Metabolic Science, University of Cambridge, Cambridge, UK

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Paolo Beck-Peccoz Department of Medical Biotechnology and Translational Medicine, University of Milan, Milano, Italy

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Krishna Chatterjee Institute of Metabolic Science, University of Cambridge, Cambridge, UK

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Impaired sensitivity to thyroid hormones encompasses disorders with defective transport of hormones into cells, reduced hormone metabolism, and resistance to hormone action. Mediated by heritable single-gene defects, these rare conditions exhibit different patterns of discordant thyroid function associated with multisystem phenotypes. In this context, challenges include ruling out other causes of biochemical discordance, making a diagnosis using clinical features together with the identification of pathogenic variants in causal genes, and managing these rare disorders with a limited evidence base. For each condition, the present guidelines aim to inform clinical practice by summarizing key clinical features and useful investigations, criteria for molecular genetic diagnosis, and pathways for management and therapy. Specific, key recommendations were developed by combining the best research evidence available with the knowledge and clinical experience of panel members, to achieve a consensus.

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Pepijn van Houten Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, the Netherlands

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James Nagarajah Roentgeninstitut Duesseldorf, Duesseldorf, Germany
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands

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Janneke E W Walraven Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands

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Martin Jaeger Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, the Netherlands

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Adriana C H van Engen-van Grunsven Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands

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Johannes W Smit Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, the Netherlands

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Romana T Netea-Maier Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, the Netherlands
Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

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Objective

Patients with non-medullary thyroid carcinoma (NMTC) that are refractory to radioactive iodine (RAI) have a poor prognosis. Strategies for restoring the ability to take up iodine, so-called redifferentiation, are promising but not suitable for all patients. Preclinical studies, in human cell lines just as in a murine model, have shown that the cardiac glycoside digoxin restored RAI uptake. This prospective single-center open-label study aimed to investigate whether treatment with digoxin could reinduce clinically relevant RAI uptake in patients with metastasized RAI-refractory NMTC.

Methods

Eight patients with metastasized RAI-refractory NMTC were included between November 2022 and June 2023. Before treatment, a baseline [123I]NaI scintigraphy was performed. Thereafter, patients were treated with digoxin for 3 weeks. Starting doses depended on age and weight. For safety reasons, the usual therapeutic range was aimed for. After 1 week, the digoxin plasma concentration was measured, and the digoxin dose was adjusted if necessary. After 3 weeks of digoxin treatment, a second [123I]NaI scintigraphy was performed. RAI uptake was compared between the two scintigraphies.

Results

Seven patients completed the digoxin treatment and were evaluable. None of the seven patients showed clinically relevant RAI uptake after digoxin treatment. No digoxin-related serious adverse events occurred during this trial.

Conclusion

Contrary to results from preclinical trials, in this trial, 3 weeks of digoxin treatment did not reinduce RAI uptake in patients with NMTC. This highlights essential challenges regarding the approach toward optimization of studies aimed to restore the RAI uptake and its therapeutic efficacy through drug repurposing.

Open access
Kenneth Ka Hei Lai Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

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Fatema Mohamed Ali Abdulla Aljufairi Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
Department of Ophthalmology, Salmaniya Medical Complex, Government Hospitals, Bahrain

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Jake Uy Sebastian Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
Department of Ophthalmology, Vicente Sotto Memorial Medical Center, Cebu City, Philippines

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Yingying Wei Department of Statistics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

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Ruofan Jia Department of Statistics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

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Karen Kar Wun Chan Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Special Administrative Region, China

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Elaine Yuen Ling Au Division of Clinical Immunology, Department of Pathology, Queen Mary Hospital, Hong Kong Special Administrative Region, China

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Alan Chun Hong Lee Division of Endocrinology and Metabolism, Department of Medicine, Queen Mary Hospital, Hong Kong Special Administrative Region, China

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Chiu Ming Ng Department of Medicine, Queen Elizabeth Hospital, Hong Kong Special Administrative Region, China

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Hunter Kwok Lai Yuen Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
Hong Kong Eye Hospital, Hong Kong Special Administrative Region, China

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Wilson Wai Kuen Yip Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Special Administrative Region, China

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Alvin Lerrmann Young Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Special Administrative Region, China

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George Pak Man Cheng Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

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Clement Chee Yung Tham Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
Hong Kong Eye Hospital, Hong Kong Special Administrative Region, China

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Chi Pui Pang Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

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Kelvin Kam Lung Chong Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
Hong Kong Eye Hospital, Hong Kong Special Administrative Region, China

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Purpose

This study aims to report correlations between thyroid-stimulating immunoglobulin (TSI) and both clinical and radiological parameters in recent-onset symptomatic thyroid eye disease (TED) patients.

Methods

A prospective cohort study of TED patients managed at the Chinese University of Hong Kong from January 2014 to May 2022. Serum TSI levels were determined with the functional assay. Outcomes included the Clinical Activity Score (CAS), marginal reflex distance1 (MRD1), extraocular muscle motility restriction (EOMy), exophthalmos, and diplopia. The radiological assessment included cross-sectional areas and signal of extraocular muscles on STIR-sequence MRI.

Results

A total of 255 (197 female) treatment-naive patients, with an average onset age of 50 ± 14 years (mean ± s.d.), were included. Elevated pre-treatment TSI level was observed in 223 (88%) patients. There was a weak positive correlation between TSI and CAS (r = 0.28, P = 0.000031), MRD1 (r = 0.17, P = 0.0080), and the size of the levator palpebrae superioris/superior rectus complex (r = 0.25, P = 0.018). No significant correlation existed between TSI and STIR signals. The AUC and optimal cut-off value for clinical active TED were 0.67 (95% CI: 0.60–0.75) and 284% (specificity: 50%, sensitivity: 85%). In total, 64 patients received intravenous methylprednisolone (IVMP) during the study interval, and they had a higher baseline TSI level than those who did not have IVMP (P = 0.000044). Serial post-IVMP TSI among the 62 patients showed a significant reduction compared to the baseline level (P < 0.001). Both the baseline and post-IVMP TSI levels, and percentages of TSI changes were comparable between patients who responded and did not respond to the first course of IVMP.

Conclusion

TSI can be a serum biomarker for the diagnosis, prognosis, and treatment response of TED. Further validation should be warranted.

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Elisa Minaldi Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Virginia Cappagli Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Loredana Lorusso Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Laura Valerio Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Carlotta Giani Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Matilde Viglione Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Laura Agate Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Eleonora Molinaro Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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Antonio Matrone Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Via Paradisa, Pisa, Italy

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

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Objective

The aim of this study was to assess the clinical impact of hand–foot syndrome (HFS) during treatment with two multikinase inhibitors, sorafenib and lenvatinib, in a large group of patients with advanced thyroid cancer. Moreover, we looked for possible associations between HFS occurrence and clinical and pathological features.

Methods

We retrospectively evaluated 239 patients with advanced thyroid cancer: 165 treated with lenvatinib and 74 with sorafenib. Statistical analyses were performed to verify which features could be correlated with HFS development.

Results

HFS was observed in 35/74 (47.4%) and in 43/165 (26.7%) patients treated with sorafenib or lenvatinib, respectively. The median latency from the drug beginning and HFS appearance was 27 days for sorafenib and 2.9 months for lenvatinib. G3/G4 toxicity was observed in 16/35 (45.7%) patients treated with sorafenib and only in 3/43 (7%) treated with lenvatinib. Drug dose reduction due to HFS was required in 19/74 (25.7%) and 3/165 (1.8%) patients treated with sorafenib and lenvatinib, respectively. HFS occurrence was significantly associated with a longer duration of therapy in both groups.

Conclusion

HFS was a frequent adverse event during both lenvatinib and sorafenib therapy, with a higher frequency and toxicity grade during sorafenib treatment. HFS was the most frequent reason for drug reduction or discontinuation in patient treated with sorafenib. Early diagnosis of HFS is important to allow early intervention, possibly in a multidisciplinary setting, and to avoid treatment discontinuation, which is highly relevant to obtain the maximum effectiveness of systemic therapy.

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Inês Cosme Department of Endocrinology, Unidade Local de Saúde Santa Maria, Lisbon, Portugal

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Ana Figueiredo Department of Endocrinology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Sara Pinheiro Department of Endocrinology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Valeriano Leite Department of Endocrinology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Graphical abstract

Abstract

Background

Thyroid carcinoma (TC) incidence increased over the past 50 years. The explanation for this is not consensual.

Objective

Compare incidental vs non-incidental TC (ITC vs NITC) regarding demographic, clinical, histological data and 5-year clinical outcomes.

Design

Retrospective analysis of 225 papillary TC (PTC) cases that completed a 5-year follow-up.

Methods

Created 2 groups: ITC (including the incidentalomas) and NITC (cases of palpable or visible nodules or with thyroid compressive complaints).

Results

Included 225 PTC (122 were ITC). There were 95 women in ITC and 78 in NITC. ITC patients were significantly older (53.3 ± 14.8 vs 47.2 ± 17.7, P = 0.006). Groups had no differences in family history of TC. ITC mean tumour size was smaller (19.1 ± 9.2 vs 28.6 ± 16.2, P < 0.01). Tumours > 20 mm comprised 36.1% of ITC and 58.2% of NITC. We found no differences in tumour multifocality, histological thyroiditis, aggressive PTC subtypes, capsule or lymph-vascular invasion and gross extrathyroidal extension. There were no differences regarding the number of patients submitted to RAI or in RAI activity. pTMN staging showed higher prevalence of T3a and T4 cases (P < 0.01), and M1 status (P = 0.025) in NITC. There were no differences in the rates of persistence of disease. Logistic regression showed that the diagnostic modality had no impact on the 5-year clinical outcome.

Conclusion

ITC patients were older and had smaller tumours. NITC showed no worst histological features or 5-year clinical outcome. Approximately, one third of ITC had diameters > 20 mm. As even large tumours can be ITC, overdiagnosis is the most likely cause of increasing incidence of TC.

Open access
Julia A Baran Division of Endocrinology and Diabetes, The Thyroid Center, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

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Mya Bojarsky Division of Endocrinology and Diabetes, The Thyroid Center, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

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Stephen Halada Division of Endocrinology and Diabetes, The Thyroid Center, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

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Julio C Ricarte-Filho Division of Endocrinology and Diabetes, The Thyroid Center, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

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Amber Isaza Division of Endocrinology and Diabetes, The Thyroid Center, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

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Aime T Franco Division of Endocrinology and Diabetes, The Thyroid Center, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

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Lea F Surrey Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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Tricia Bhatti Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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Zubair Baloch Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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N Scott Adzick Department of Surgery, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

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Sogol Mostoufi-Moab Division of Endocrinology and Diabetes, The Thyroid Center, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

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Ken Kazahaya Division of Pediatric Otolaryngology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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Andrew J Bauer Division of Endocrinology and Diabetes, The Thyroid Center, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

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Objective

The American Thyroid Association (ATA) Pediatric Guidelines recommend selective, prophylactic central neck dissection (pCND) for patients with papillary thyroid carcinoma (PTC) based on tumor focality, tumor size, and the surgeon’s experience. With the expansion of pre-surgical somatic oncogene testing and continued controversy over the benefits of pCND, oncogenic alteration data may provide an opportunity to stratify pCND. This study compared lymph node (LN) involvement in pediatric patients with PTC between tumors with low- and high-invasive-associated alterations to explore the potential utility of preoperative oncogenic alterations in the stratification of pCND.

Methods

This is retrospective cohort study of pediatric patients who underwent somatic oncogene testing post thyroidectomy for PTC between July 2003 and July 2022.

Results

Of 192 eligible PTC patients with postoperative somatic oncogene data, 19 tumors harbored somatic alterations associated with low-invasive disease (19/192, 10%), and 128 tumors harbored a BRAFV600E alteration (45/192, 23%) or an oncogenic fusion (83/192, 43%). Tumors with low-invasive alterations were less likely to present malignant preoperative cytology (2/18, 11%) than those with high-invasive alterations (97/124, 78%; P < 0.001). Twelve patients with low-invasive alterations had LNs dissected from the central neck (12/19, 63%) compared to 127 patients (127/128, 99%) with high-invasive alterations. LN metastasis was identified in two patients with low-invasive alterations (2/19, 11%) compared to 107 patients with high-invasive alterations (107/128, 84%; P < 0.001).

Conclusion

Pediatric patients with low-invasive somatic oncogenic alterations are at low risk for metastasis to central neck LNs. Our findings suggest that preoperative knowledge of somatic oncogene alterations provides objective data to stratify pediatric patients who may not benefit from pCND.

Open access
Fabio Hecht Université Paris-Saclay, Orsay, France
UMR 9019 CNRS F-94805 Villejuif, France
Gustave Roussy, Villejuif, France

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Laura Valerio Université Paris-Saclay, Orsay, France
UMR 9019 CNRS F-94805 Villejuif, France
Gustave Roussy, Villejuif, France

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Carlos Frederico Lima Gonçalves Université Paris-Saclay, Orsay, France
UMR 9019 CNRS F-94805 Villejuif, France
Gustave Roussy, Villejuif, France

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Marylin Harinquet Université Paris-Saclay, Orsay, France
UMR 9019 CNRS F-94805 Villejuif, France
Gustave Roussy, Villejuif, France

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Rabii Ameziane El Hassani Laboratoire de Biologie des Pathologies Humaines ‘BioPatH’, Université Mohammed V de Rabat, Faculté des Sciences, BP1014 Rabat, 10001, Morocco

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Denise P Carvalho Laboratório de Fisiologia Endócrina Doris Rosenthal, nstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

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Stephane Koundrioukoff UMR 9019 CNRS F-94805 Villejuif, France
Gustave Roussy, Villejuif, France
Sorbonne Université, Paris, France

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Jean-Charles Cadoret Université Paris Cité, CNRS, Institut Jacques Monod, Paris, France

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Corinne Dupuy Université Paris-Saclay, Orsay, France
UMR 9019 CNRS F-94805 Villejuif, France
Gustave Roussy, Villejuif, France

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Objective

Ionizing radiation generates genomic instability by promoting the accumulation of chromosomal rearrangements. The oncogenic translocation RET/PTC1 is present in more than 70% of radiation-induced thyroid cancers. Both RET and CCDC6, the genes implicated in RET/PTC1, are found within common fragile sites – chromosomal regions prone to DNA breakage during slight replication stress. Given that irradiated cells become more susceptible to genomic destabilization due to the accumulation of replication-stress-related double-strand breaks (DSBs), we explored whether RET and CCDC6 exhibit DNA breakage under replicative stress several days post-irradiation of thyroid cells.

Methods

We analyzed the dynamic of DNA replication in human thyroid epithelial cells (HThy-ori-3.1) 4 days post a 5-Gy exposure using molecular DNA combing. The DNA replication schedule was evaluated through replication-timing experiments. We implemented a ChIP-qPCR assay to determine whether the RET and CCDC6 genes break following irradiation.

Results

Our study indicates that replicative stress, occurring several days post-irradiation in thyroid cells, primarily causes DSBs in the RET gene. We discovered that both the RET and CCDC6 genes undergo late replication in thyroid cells. However, only RET’s replication rate is notably delayed after irradiation.

Conclusion

The findings suggest that post-irradiation in the RET gene causes a breakage in the replication fork, which could potentially invade another genomic area, including CCDC6. As a result, this could greatly contribute to the high prevalence of chromosomal RET/PTC rearrangements seen in patients exposed to external radiation.

Open access
Haiyang Zhang Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China

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Shuo Wu Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China

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Shuyu Hu Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China

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Xianqun Fan Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China

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Xuefei Song Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China

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Tienan Feng Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Huifang Zhou Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China

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Background

Thyroid eye disease (TED) is an autoimmune orbital disease, with intravenous glucocorticoid (IVGC) therapy as the first-line treatment. Due to uncertain response rates and possible side effects, various prediction models have been developed to predict IVGC therapy outcomes.

Methods

A thorough search was conducted in PubMed, Embase, and Web of Science databases. Data extraction included publication details, prediction model content, and performance. Statistical analysis was performed using R software, including heterogeneity evaluation, publication bias, subgroup analysis, and sensitivity analysis. Forest plots were utilized for result visualization.

Results

Of the 12 eligible studies, 47 prediction models were extracted. All included studies exhibited a low-to-moderate risk of bias. The pooled area under the receiver operating characteristic curve (AUC) and the combined sensitivity and specificity for the models were 0.81, 0.75, and 0.79, respectively. In view of heterogeneity, multiple meta-regression and subgroup analysis were conducted, which showed that marker and modeling types may be the possible causes of heterogeneity (P < 0.001). Notably, imaging metrics alone (AUC = 0.81) or clinical characteristics combined with other markers (AUC = 0.87), incorporating with multivariate regression (AUC = 0.84) or radiomics analysis (AUC = 0.91), yielded robust and reliable prediction outcomes.

Conclusion

This meta-analysis comprehensively reviews the predictive models for IVGC therapy response in TED. It underscores that integrating clinical characteristics with laboratory or imaging indicators and employing advanced techniques like multivariate regression or radiomics analysis significantly enhance the efficacy of prediction. Our research findings offer valuable insights that can guide future studies on prediction models for IVGC therapy in TED.

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Andrea Leoncini Clinic for Radiology, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland

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Chiara Camponovo Thyroid Unit, Clinic for Endocrinology and Diabetology, Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland

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Gaetano Paone Clinic of Nuclear Medicine, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland
Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland

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Elena Gamarra Thyroid Unit, Clinic for Endocrinology and Diabetology, Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland

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Giorgio Treglia Clinic of Nuclear Medicine, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland
Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland
Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland

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Pierpaolo Trimboli Thyroid Unit, Clinic for Endocrinology and Diabetology, Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland
Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland

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Objective

Thyroid nodule (TN) is usually managed according to Thyroid Imaging And Reporting Data Systems (TIRADS) with the major aim to reduce as much as possible unnecessary fine-needle aspiration cytologies (UN-FNACs). Since the assessment of autonomously functioning thyroid nodule (AFTN) according to TIRADS is heterogeneous, that virtually benign entity may increase the rate of UN-FNAC. This study retrospectively analyzed the appropriateness of TIRADS-based FNAC indication in AFTNs, also looking at the impact of TSH and nodule size.

Methods

Cases diagnosed with AFTN on scintigraphy were searched. Patients who had undergone AFTN treatment, were on medications or supplementation that could affect thyroid function, or had multiple AFTNs were excluded. The AFTNs were assessed according to ACR-TIRADS.

Results

Forty-eight AFTNs were included of which 37.5% had FNAC indication according to TIRADS. The FNAC indication rate in the case of TSH lower than 0.4 mIU/L was significantly higher than in other cases (P = 0.0078). The most accurate TSH cut-off and AFTN size associated with UN-FNAC were ≤ 0.41 mIU/L and > 22 mm, respectively. The multivariate analysis showed that both TSH and nodule size were independent predictors of UN-FNAC with OR of 6.65 and 6.46, respectively. According to these data, the rate of FNAC indication dropped to 4.16%.

Conclusion

Inappropriate FNACs in AFTNs are primarily observed in patients with low TSH and large AFTN. Since these cases typically undergo scintigraphy, the risk of TIRADS-based UN-FNAC is clinically negligible. There is no need for integrating other imaging procedures into the TIRADS model.

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