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Jingyue Chen Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Affiliated Hospital of China Medical University, Shenyang, China

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Chenyan Li Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Affiliated Hospital of China Medical University, Shenyang, China

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Weiping Teng Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Affiliated Hospital of China Medical University, Shenyang, China

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Zhongyan Shan Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Affiliated Hospital of China Medical University, Shenyang, China

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Jun Jin Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Yining Wei Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Jing Sun Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Yushu Li Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Affiliated Hospital of China Medical University, Shenyang, China

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Huifang Zhou Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Objective

The management of thyroid eye disease (TED) has undergone significant changes for decades. The study sought to investigate current clinical practice on the management of TED in China.

Methods

An online questionnaire survey was conducted from April to May 2023. The questionnaire involved diagnostic criteria for TED, multidisciplinary treatment (MDT) collaboration, and treatment preference for mild, moderate, and severe TED.

Results

A total of 289 questionnaires were collected, with 165 from endocrinologists and 124 from ophthalmologists. Only 36.7% of participants claimed there was an MDT clinical pattern for TED in their institutions. The coverage of biological agents was around 10% or lower. These were distinctly lower than in Western countries. About 62.6% of participants believed the incidence of TED has increased in recent years. Imaging techniques were used widely to assist in the diagnosis of TED. However, there was still controversy regarding the definition of proptosis in the Chinese population. Most doctors managed risk factors and provided orbital supportive treatments of artificial tears and glasses. For mild active TED, endocrinologists (39.4%) were inclined to recommend therapy for hyperthyroidism alone, while ophthalmologists (43.6%) preferred orbital corticosteroid injections. Currently, the most widely used treatment for moderate to severe active TED was high-dose intravenous corticosteroid (94.8%), while orbital radiotherapy combined with immunosuppressive agents was the most recognized second-line therapy (43.6%).

Conclusion

The study documented the consistency and differences between current clinical practices in the management of TED in China and the recently updated guidelines. There was a remarkable difference between ophthalmology and endocrinology departments, warranting management optimization.

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Line Tang Møllehave Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Nils Knudsen Department of Endocrinology, Bispebjerg University Hospital, University of Copenhagen, Denmark

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Allan Linneberg Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Inge Bülow Pedersen Department of Endocrinology and Medicine, Aalborg University Hospital, Aalborg, Denmark

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Gitte Ravn-Haren Research Group for Risk Benefit, National Food Institute, Technical University of Denmark, Lyngby, Denmark

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Anja Lykke Madsen Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Allan Carlé Department of Endocrinology and Medicine, Aalborg University Hospital, Aalborg, Denmark

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Charlotte Cerqueira The Danish Clinical Quality Program – National Clinical Registries (RKKP), Denmark

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Anne Krejbjerg Department of Oncology, Aalborg University Hospital, Aalborg, Denmark

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Lone Banke Rasmussen Independent researcher, Klemensker, Denmark

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Lars Ovesen Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Hans Perrild Department of Endocrinology, Bispebjerg University Hospital, University of Copenhagen, Denmark

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Lena Bjergved Sigurd Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Internal Medicine, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark

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Betina Heinsbæk Thuesen Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Pernille Vejbjerg Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Torben Jørgensen Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Due to mild-to-moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from the World Health Organization, the Danish investigation on iodine intake and thyroid disease (DanThyr) was established to monitor the effect on thyroid health and disease. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild–moderate iodine deficiency to low adequacy. The level of thyroglobulin and thyroid volume decreased following IF, and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid-stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program – as IF – is initiated.

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Carla Colombo Endocrine Oncology Unit, 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 Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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Massimiliano Succi Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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

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Matteo Trevisan Endocrine Oncology Unit, 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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Claudia Moneta Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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Laura Fugazzola Endocrine Oncology Unit, 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

Fatigue is a frequent adverse event during systemic treatments for advanced thyroid cancer, often leading to reduction, interruption, or discontinuation. We were the first group to demonstrate a correlation between fatigue and primary adrenal insufficiency (PAI).

Aim

The objective was to assess the entire adrenal function in patients on systemic treatments.

Methods

ACTH, cortisol and all the hormones produced by the adrenal gland were evaluated monthly in 36 patients (25 on lenvatinib, six on vandetanib, and five on selpercatinib). ACTH stimulation tests were performed in 26 cases.

Results

After a median treatment period of 7 months, we observed an increase in ACTH values in 80–100% of patients and an impaired cortisol response to the ACTH test in 19% of cases. Additionally, dehydroepiandrosterone sulphate, ∆-4-androstenedione and 17-OH progesterone levels were below the median of normal values in the majority of patients regardless of the drug used. Testosterone in females and oestradiol in males were below the median of normal values in the majority of patients on lenvatinib and vandetanib. Finally, aldosterone was below the median of the normal values in most cases, whilst renin levels were normal. Metanephrines and normetanephrines were always within the normal range. Replacement therapy with cortisone acetate improved fatigue in 14/17 (82%) patients with PAI.

Conclusion

Our data confirm that systemic treatments for advanced thyroid cancer can lead to impaired cortisol secretion. A reduction in the other hormones secreted by the adrenal cortex has been first reported and should be considered in the more appropriate management of these fragile patients.

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Véronique Raverot Hospices Civils de Lyon, Groupement Hospitalier Est, LBMMS, Centre de biologie et de pathologie Est, Lyon, France

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Stéphanie Metrat Hospices Civils de Lyon, Groupement Hospitalier Est, LBMMS, Centre de biologie et de pathologie Est, Lyon, France

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Pauline Perrin Hospices Civils de Lyon, Groupement Hospitalier Est, LBMMS, Centre de biologie et de pathologie Est, Lyon, France

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Juliette Abeillon Hospices Civils de Lyon, Groupement Hospitalier Est, Fédération d’Endocrinologie, Lyon, France

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Hélène Lasolle Hospices Civils de Lyon, Groupement Hospitalier Est, Fédération d’Endocrinologie, Lyon, France

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

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

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

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

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

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

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

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

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

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

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

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Context

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

Case presentation and results

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

Conclusion

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

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

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

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

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

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

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

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

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

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

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

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

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Background

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

Aim

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

Methods

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

Results

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

Conclusion

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

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

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

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

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

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

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

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

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

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

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

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Objective

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

Methods

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

Results

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

Conclusion

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

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Ana Isabel Alvarez-Mancha A Alvarez-Mancha, Department of Medicine, University of Malaga, 29010 Malaga, Spain. b, University of Malaga, Malaga, Spain

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Isabel Mancha-Doblas I Mancha-Doblas, Department of Medicine, University of Malaga, 29010 Malaga, Spain. , University of Malaga, Malaga, Spain

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María Molina-Vega M Molina-Vega, Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Málaga, Spain, University Hospital Virgen de la Victoria, Malaga, Spain

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Diego Fernández-García D Fernández-García, Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Málaga, Spain, University Hospital Virgen de la Victoria, Malaga, Spain

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Ana María Gómez-Pérez A Gómez-Pérez, Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Málaga, Spain, University Hospital Virgen de la Victoria, Malaga, Spain

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Elena Gallego E Gallego, Department of Medicine, University of Malaga, 29010 Malaga, Spain, University of Malaga, Malaga, Spain

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María Victoria Ortega-Jiménez M Ortega-Jiménez , Department of Medicine, University of Malaga, 29010 Malaga, Spain, University of Malaga, Malaga, Spain

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Isabel Hierro-Martín I Hierro-Martín, Department of Pathology, Virgen de la Victoria University Hospital, University Hospital Virgen de la Victoria, Malaga, Spain

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Francisco J Tinahones F Tinahones, Department of Medicine, University of Malaga, 29010 Malaga, Spain, University of Malaga, Malaga, Spain

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Objective: The objective of this study was to analyze the evolution in the diagnosis and management of indeterminate thyroid nodules over three time periods.

Methods: 3020 patients with thyroid nodules underwent cytological evaluation during three periods (2006-2008, 2012-2014, 2017-2019). Distribution of diagnostic cytologies, risk of malignancy, diagnostic performance indices of FNA, and cytologic-histologic correlation in indeterminate cytologies were analyzed.

Results: only 2.2% of cytology tests were insufficient for a diagnosis. 86.9% cytologies were benign, 1.7% malignant, and 11.4% indeterminate. Indeterminate cytology rates were 15.9% (2006-2008), 10.1% (2012-2014), and 10% (2017-2019). Surgery was performed in 13% of benign cytology, result-ing in malignant histology in 2.7%. All malignant and suspicious cytologies underwent surgery: malig-nancy confirmed in 98% and 77% of cases, respectively.

All 'indeterminate with atypia' cytologies (2006-2008) and Bethesda IV (2012-2014; 2017-2019) un-derwent surgery, with malignancy confirmed in 19.6%, 43.8%, and 25.7%, respectively. In the 'inde-terminate without atypia' category (2006-2008) and Bethesda III (2012-2014; 2017-2019), diagnostic surgery was performed in 57.7%, 78.6%, and 59.4%, respectively, with malignancy confirmed in 3.3%, 20.5%, and 31.6%. The FNA sensitivity was 91.6% with a negative predictive value greater than 96% in all periods. The specificity exceeded 75% in the last two periods.

Conclusion: Bethesda system reduces indeterminate cytologies and improves the accuracy of FNA diagnosis. We reported a higher proportion of malignancy than expected in Bethesda III, underscoring the importance of having institution-specific data to guide decision-making. However, there is a need for risk stratification tools that allow for conservative management in low-risk cases.

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Maria Mavromati M Mavromati, University of Geneva Faculty of Medicine, Geneva, Switzerland

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Verdiana Caironi V Caironi, Internal Medicine, Lugano Regional Hospital, Lugano, Switzerland

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Essia Saiji E Saiji, Pathology, Geneva University Hospitals, Geneva, Switzerland

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Maria-Isabel Vargas M Vargas, Neuroradiology, Geneva University Hospitals, Geneva, Switzerland

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Shahan Momjian S Momjian, Neurosurgery, Geneva University Hospitals, Geneva, Switzerland

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Stephanie Andrade-Lopes S Andrade-Lopes, Endocrinology, Diabetology, Nutrition and Therapeutic Education, Geneva University Hospitals, Geneva, Switzerland

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Capucine Gubert C Gubert, Internal Medicine, Geneva University Hospitals, Geneva, Switzerland

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Marco Stefano Demarchi M Demarchi, Thoracic and Endocrine Surgery, Geneva University Hospitals, Geneva, Switzerland

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Ismini Mainta I Mainta, Nuclear Medicine, Geneva University Hospitals, Geneva, Switzerland

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François R. Jornayvaz F Jornayvaz, Endocrinology Diabetology Nutrition and Therapeutic Education, Geneva University Hospitals, Geneve, Switzerland

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Kaveh Samii K Samii, Hematology, Geneva University Hospitals, Geneva, Switzerland

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Grégoire Stalder G Stalder, Service and Central Laboratory of Hematology, Lausanne University Hospital, Lausanne, Switzerland

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Sophie Leboulleux S Leboulleux, Endocrinology, Diabetology, Nutrition and Therapeutic Education, Geneva University Hospitals, Geneva, Switzerland

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Langerhans cell histiocytosis (LCH) may present as unifocal disease of the suprasellar region, with symptoms and signs of hypopituitarism, arginine vasopressin deficiency (AVP-D) and weight gain. Transcranial biopsy is necessary, to define diagnosis and guide treatment decisions, but is associated with significant morbidity. We describe a patient with Hashimoto thyroiditis and a single hypothalamic mass in whom LCH diagnosis was done through thyroid fine-needle aspiration cytology (FNAC) performed despite nonspecific findings in thyroid imaging, on the basis of a slightly elevated [18F]-fluorodeoxyglucose avidity on positron emission tomography/-computed tomography (FDG-PET/-CT), and volume increase during follow-up.

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Stan R Ursem S Ursem, Amsterdam University Medical Centers, Amsterdam, 1105AZ, Netherlands

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Anita Boelen A Boelen, Laboratory Medicine, Endocrinology Laboratory, Amsterdam UMC Locatie AMC, Amsterdam, 1105 AZ, Netherlands

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Eveline Bruinstroop E Bruinstroop, Endocrinology and Metabolism, Amsterdam UMC Locatie AMC, Amsterdam, 1105 AZ, Netherlands

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Petra J.m. Elders P Elders, Department of General Practice, Amsterdam UMC Location Vrije Universiteit, Amsterdam, Netherlands

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Jacobijn Gussekloo J Gussekloo, LUMC Center for Medicine for older people, Leiden Universitair Medisch Centrum, Leiden, Netherlands

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Rosalinde K. E. Poortvliet R Poortvliet, LUMC Center for Medicine for older people, Leiden Universitair Medisch Centrum, Leiden, Netherlands

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Annemieke C. Heijboer A Heijboer, Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam, 1105AZ, Netherlands

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Wendy P.j. den Elzen W den Elzen, Department of Clinical Chemistry, Amsterdam UMC location University of Amsterdam, Amsterdam, Netherlands

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Background

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

Methods

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

Results

Of the 2,624 records screened, 22 guidelines were included, which were published between 2007 and 2021. Guideline quality was generally intermediate to low. Diagnostic approaches differed substantially, particularly in the extent of recommended testing. Treatment initiation depended on TSH levels, age, and comorbidities, but the level of detail regarding defining precise comorbidities varied. Recommendations for monitoring intervals for follow-up ranged from three to twelve months.

Conclusions

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

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