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Ilaria Muller Department of Clinical Sciences and Community Health, University of Milan, Italy
Endocrinology Unit, Graves’ Orbitopathy Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Sara Maioli Department of Clinical Sciences and Community Health, University of Milan, Italy

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Mirco Armenti Department of Clinical Sciences and Community Health, University of Milan, Italy

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Laura Porcaro Department of Clinical Sciences and Community Health, University of Milan, Italy

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Nicola Currò Endocrinology Unit, Graves’ Orbitopathy Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Ophthalmology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Elisabetta Iofrida Department of Specialistic Surgical Sciences, Otolaryngology and Head and Neck Surgery, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Lorenzo Pignataro Department of Clinical Sciences and Community Health, University of Milan, Italy
Department of Specialistic Surgical Sciences, Otolaryngology and Head and Neck Surgery, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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

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

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Jens Geginat Department of Clinical Sciences and Community Health, University of Milan, Italy
National Institute of Molecular Genetics (INGM) “Romeo and Enrica Invernizzi”, Milan, Italy

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Mario Salvi Endocrinology Unit, Graves’ Orbitopathy Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Introduction

Secondary thyroid autoimmunity, especially Graves’ disease (GD), frequently develops in patients with multiple sclerosis (MS) following alemtuzumab treatment (ALTZ; anti-CD52). Thyroid eye disease (TED) can also develop, and rituximab (RTX; anti-CD20) is a suitable treatment.

Case presentation

A 37-year-old woman with MS developed steroid-resistant active moderate-to-severe TED 3 years after ALTZ, that successfully responded to a single 500 mg dose of i.v. RTX. Before RTX peripheral B-cells were low, and were totally depleted immediately after therapy. Follow-up analysis 4 years post ALTZ and 1 year post RTX showed persistent depletion of B cells, and reduction of T regulatory cells in both peripheral blood and thyroid tissue obtained at thyroidectomy.

Conclusion

RTX therapy successfully inactivated TED in a patient with low B-cell count derived from previous ALTZ treatment. B-cell depletion in both thyroid and peripheral blood was still present 1 year after RTX, indicating a likely cumulative effect of both treatments.

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Chen Jingyue C Jingyue, 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, 沈阳市, 110001, China

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Chenyan Li C Li, Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, Shenyang, China

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Weiping Teng W Teng, China Medical University, Shenyang, 110000, China

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Zhongyan Shan Z Shan, Shenyang, United Kingdom of Great Britain and Northern Ireland

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

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

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

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Yushu Li Y Li, Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, Shenyang, China

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Huifang Zhou H Zhou, Department of Ophthalmology, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, 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 36.68% participants claimed there was MDT clinical pattern for TED in their institutions. The coverage of biologic agents was around 10% or lower. These were distinctly lower than western countries. 62.63% 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 Chinese population. Most doctors managed risk factors and provided orbital supportive treatments of artificial tears and glasses. For mild active TED, endocrinologists (39.39%) inclined to recommend therapy for hyperthyroidism alone and ophthalmologists (43.55%) preferred orbital corticosteroid injections. Currently, the most widely used treatment for moderate to severe active TED was high-dose intravenous corticosteroid (94.81%), while orbital radiotherapy combined with immunosuppressive agents was the most recognized second-line therapy (43.60%).

Conclusion: The study documented the consistency and differences between current clinical practices on 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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Peter PA Smyth UCD School of Medicine, University College Dublin, Dublin, Ireland

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Colin D O’Dowd Ryan Institute’s Centre for Climate & Air Pollution Studies, School of Physics, University of Galway, Ireland

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Global warming is now universally acknowledged as being responsible for dramatic climate changes with rising sea levels, unprecedented temperatures, resulting fires and threatened widespread species loss. While these effects are extremely damaging, threatening the future of life on our planet, one unexpected and paradoxically beneficial consequence could be a significant contribution to global iodine supply. Climate change and associated global warming are not the primary causes of increased iodine supply, which results from the reaction of ozone (O3) arising from both natural and anthropogenic pollution sources with iodide (I) present in the oceans and in seaweeds (macro- and microalgae) in coastal waters, producing gaseous iodine (I2). The reaction serves as negative feedback, serving a dual purpose, both diminishing ozone pollution in the lower atmosphere and thereby increasing I2. The potential of this I2 to significantly contribute to human iodine intake is examined in the context of I2 released in a seaweed-abundant coastal area. The bioavailability of the generated I2 offers a long-term possibility of increasing global iodine status and thereby promoting thyroidal health. It is hoped that highlighting possible changes in iodine bioavailability might encourage the health community to address this issue.

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Georgios Kostopoulos Department of Endocrinology and Metabolism, Ippokratio General Hospital of Thessaloniki, Greece

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Grigoris Effraimidis Department of Endocrinology and Metabolic Diseases, Larissa University Hospital, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece

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Atrial fibrillation (AF) is a common condition with a global estimated prevalence of 60 million cases, and the most common cardiac complication of hyperthyroidism, occurring in 5–15% of overtly hyperthyroid patients. Additionally, subclinical hyperthyroidism and high-normal free T4 have been associated with an increased risk in the development of AF. Hyperthyroidism-related AF is a reversible cause of AF, and the majority of patients spontaneously revert to sinus rhythm in 4–6 months during or after restoration of euthyroidism. Therefore, restoring thyroid function is an indispensable element in hyperthyroidism-related AF management. Rate control with beta-blockers consists another first-line therapy, reserving rhythm control in cases of persistent hyperthyroidism-related AF. It is still controversial whether hyperthyroidism is an independent risk factor of stroke in nonvalvular AF. As a result, initiating anticoagulation should be guided by the clinical thromboembolic risk score CHA2DS2-VASc score in the same way it is applied in patients with non-hyperthyroidism-related AF. Treatment with the novel direct oral anticoagulants appears to be as beneficial and may be safer than warfarin in patients with hyperthyroidism-related AF. In this review, we address the epidemiology, prognosis, and diagnosis of hyperthyroidism-related AF, and we discuss the management strategies and controversies in patients with hyperthyroidism-related AF.

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Tommaso Piticchio Endocrinology Section, Department of Clinical and Experimental Medicine, Garibaldi Nesima Hospital, University of Catania, Catania, Italy
Servizio di Endocrinologia e Diabetologia, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland

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Gilles Russ Department of Thyroid and Endocrine Tumor Diseases, La Pitie-Salpetriere Hospital, 83 Bd de l’Hopital, Paris, France

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Maija Radzina Riga Stradins University, Radiology Research Laboratory, Riga, Latvia
University of Latvia, Faculty of Medicine, Riga, Latvia

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Francesco Frasca Endocrinology Section, Department of Clinical and Experimental Medicine, Garibaldi Nesima Hospital, University of Catania, Catania, Italy

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Cosimo Durante Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

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Pierpaolo Trimboli Servizio di Endocrinologia e Diabetologia, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland
Facoltà di Scienze Biomediche, Università della Svizzera Italiana (USI), Lugano, Switzerland

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Context

Ultrasound-based risk stratification systems (Thyroid Imaging Reporting and Data Systems (TIRADSs)) of thyroid nodules (TNs) have been implemented in clinical practice worldwide based on their high performance. However, it remains unexplored whether different TIRADSs perform uniformly across a range of TNs in routine practice. This issue is highly relevant today, given the ongoing international effort to establish a unified TIRADS (i.e. I-TIRADS), supported by the leading societies specializing in TNs. The study aimed to conduct a direct comparison among ACR-, EU-, and K-TIRADS in the distribution of TNs: (1) across the TIRADS categories, and (2) based on their estimated cancer risk.

Methods

A search was conducted on PubMed and Embase until June 2023. Original studies that sequentially assessed TNs using TIRADSs, regardless of FNAC indication, were selected. General study characteristics and data on the distribution of TNs across TIRADSs were extracted.

Results

Seven studies, reporting a total of 41,332 TNs, were included in the analysis. The prevalence of ACR-TIRADS 1–2 was significantly higher than that of EU-TIRADS 2 and K-TIRADS 2, with no significant difference observed among intermediate- and high-risk categories of TIRADSs. According to malignancy risk estimation, K-TIRADS often classified TNs as having more severe risk, ACR-TIRADS as having moderate risk, and EU-TIRADS classified TNs as having lower risk.

Conclusion

ACR-, EU-, and K-TIRADS assess TNs similarly across their categories, with slight differences in low-risk classifications. Despite this, focusing on cancer risk estimation, the three TIRADSs assess TNs differently. These findings should be considered as a prerequisite for developing the I-TIRADS.

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Thea Riis Department of Endocrinology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark

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Steen Joop Bonnema Department of Endocrinology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark

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Thomas Heiberg Brix Department of Endocrinology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark

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Lars Folkestad Department of Endocrinology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark

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Objective

Cancer is the second most common cause of death worldwide. It is currently debated whether thyroid dysfunction is a modifiable cancer risk factor. Our aim was to evaluate the risk of cancer in patients with hyperthyroidism.

Methods

This is a register-based nationwide cohort study of individuals with a diagnosis of hyperthyroidism. Each hyperthyroid case was matched with four reference individuals according to age and sex. Using Fine and Gray competing risk regression models, we studied the association of hyperthyroidism and subsequent all-cause cancer diagnoses, adjusted for preexisting morbidity. Sub-analyses were stratified for cause of hyperthyroidism (Graves’ disease and toxic nodular goiter, age when diagnosed with hyperthyroidism, sex, and cancer localization (lung, prostate, breast, and colorectal cancer)).

Results

The cohort consisted of 95,469 patients with hyperthyroidism (followed for a median of 10.9 years (range: 5.2–17.2)), and 364,494 reference individuals (followed for a median of 11.2 years (range: 5.4–17.4)). Hyperthyroidism was associated with increased all-cause cancer risk (sub-distribution hazard ratio (SHR): 1.12; 95% CI: 1.10–1.14), as well as an increased risk of breast (SHR: 1.07; 95% CI: 1.02–1.13), lung (SHR: 1.20; 95% CI: 1.16–1.26), and prostate cancer (SHR: 1.10; 95% CI: 1.02–1.19), but not colorectal cancer (SHR: 1.04; 95% CI: 0.99–1.09). Sub-analyses stratified for age when diagnosed with hyperthyroidism and cause of hyperthyroidism yielded similar results.

Conclusion

In this register-based study, patients with hyperthyroidism had an increased risk of cancer, in particular lung, prostate, and breast cancer. Whether a causal link exists remains to be proven.

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Victor J M Pop Department of Medical Psychology, Tilburg University, The Netherlands

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Johannes G Krabbe Department of Clinical Chemistry and Laboratory Medicine, Medisch Spectrum Twente, Medlon BV, Enschede, The Netherlands

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Maarten Broeren Department of Clinical Chemistry, Maxima Medical Centre, Veldhoven, The Netherlands

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Wilmar Wiersinga Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands

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Margaret P Rayman Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK

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Objective

Pregnancy is a state of physiological inflammation facilitating implantation. Early isolated hypothyroxinaemia (IH) and increased inflammation (including obesity) have been associated with severe obstetric complications. The current study evaluated the association between IH, low ferritin and inflammation parameters (interleukin 6 (IL-6), C-reactive protein (CRP), human chorionic gonadotrophin (hCG) and obesity. Moreover, the course of these parameters throughout pregnancy was evaluated in relation to IH.

Methods

In the cross-sectional study (A) at 12 weeks, 2759 women participated and 2433 participated in the longitudinal study (B) with assessments at 12, 20 and 28 weeks gestation. At the first trimester, 122 (4.4%) IH women (free thyroxine (FT4) <5th percentile, normal TSH levels) were compared with 2114 (76.6%) reference women (FT4 between tenth and 90th percentiles, normal thyrotrophin (TSH) levels), in study B these figures were 99 (4.1%) and 1847 (75.9%), respectively.

Results

Cross-sectionally, compared to reference women, IH was independently associated with low ferritin (<5th percentile, OR: 2.6, 95% CI: 1.4–4.9), high CRP (>95th percentile: OR: 1.9, 95% CI: 1.04–3.7), low hCG (<median, OR: 2.1, 95% CI: 1.40–3.16), obesity (BMI > 30, OR: 1.7, 95% CI: 1.12.9) and higher age (OR: 1.1, 95% CI: 1.04–1.15). Longitudinally, compared to reference women, women with IH at 12 weeks gestation showed persistently and significantly lower ferritin and hCG levels, and persistently higher CRP and IL-6 levels throughout gestation.

Conclusion

Gestational IH could be viewed as a condition of increased inflammation, as reported in non-thyroidal illness syndrome. Less favourable inflammation parameters and low iron status during early gestation in IH women seem to persist throughout gestation.

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Carla Colombo C Colombo, Endocrine Oncology Unit, Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Milano, Italy

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

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

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

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Matteo Trevisan M Trevisan, Department of Biotechnology and Translational Medicine, University of Milan, 20100, Milan, Italy., University of Milan, Milano, Italy

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Claudia Moneta C Moneta, Department of Biotechnology and Translational Medicine, University of Milan, 20100, Milan, Italy. , University of Milan, Milan, Italy

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Laura Fugazzola L Fugazzola, Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, 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: 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, 6 on vandetanib, and 5 on selpercatinib). ACTH stimulation test was 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 ACTH test in 19% of cases. Additionally, dehydroepiandrosterone sulphate, ∆-4-Androstenedione and 17-OH progesterone levels were below the median of normal values (n.v.) in the majority of patients regardless of the drug used. Testosterone in females and oestradiol in males were below the median of n.v. in the majority of patients on lenvatinib and vandetanib. Finally, aldosterone was below the median of the n.v. in most cases, while 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.

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

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Ángel García-Aldea Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain

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Marina Guillén-Yunta Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain

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Víctor Valcárcel-Hernández Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain

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Ana Montero-Pedrazuela Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain

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Ana Guadaño-Ferraz Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain

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Soledad Bárez-López Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain

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Thyroid hormones play an important role during the development and functioning of the different sensory systems. In order to exert their actions, thyroid hormones need to access their target cells through transmembrane transporter proteins, among which the monocarboxylate transporter 8 (MCT8) stands out for its pathophysiological relevance. Mutations in the gene encoding for MCT8 lead to the Allan–Herndon–Dudley syndrome (AHDS), a rare disease characterised by severe neuromotor and cognitive impairments. The impact of MCT8 deficiency in the neurosensory capacity of AHDS patients is less clear, with only a few patients displaying visual and auditory impairments. In this review we aim to gather data from different animal models regarding thyroid hormone transport and action in the different neurosensory systems that could aid to identify potential neurosensorial alterations in MCT8-deficient patients.

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Leonidas Duntas Evgenideion Hospital, Unit of Endocrinology, Diabetes and Metabolism, National and Kapodeistrian University of Athens, Greece

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