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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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Sang-Hyeon Ju Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea

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Yong Bae Ji Department of Otolaryngology–Head and Neck Surgery, Hanyang University College of Medicine, Seoul, Republic of Korea

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Minchul Song Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea

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Joung Youl Lim Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea

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Da Beom Heo Department of Otorhinolaryngology–Head and Neck Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea

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Min-Gyu Kim Department of Otorhinolaryngology–Head and Neck Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea

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Jae Won Chang Department of Otorhinolaryngology–Head and Neck Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea
Department of Otorhinolaryngology–Head and Neck Surgery, Chungnam National University College of Medicine, Daejeon, Republic of Korea

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Ho-Ryun Won Department of Otorhinolaryngology–Head and Neck Surgery, Chungnam National University College of Medicine, Daejeon, Republic of Korea
Department of Otorhinolaryngology–Head and Neck Surgery, Chungnam National University Sejong Hospital, Sejong, Republic of Korea

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Yea Eun Kang Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea

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Eu Jeong Ku Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea

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Mijin Kim Department of Internal Medicine, Pusan National University Hospital, Busan, Republic of Korea

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Eun Kyung Lee Department of Internal Medicine, Center for Thyroid Cancer, National Cancer Center, Goyang-si, Republic of Korea

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June Young Choi Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea

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Hyeong Won Yu Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea

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Young Joo Park Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

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Jun-Ho Choe Division of Endocrine Surgery, Department of Surgery, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea

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Bon Seok Koo Department of Otorhinolaryngology–Head and Neck Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea
Department of Otorhinolaryngology–Head and Neck Surgery, Chungnam National University College of Medicine, Daejeon, Republic of Korea

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the MASTER study group †
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the MASTER study group

Objective

Active surveillance (AS) is generally accepted as an alternative to immediate surgery for papillary thyroid carcinoma (PTC) measuring ≤1.0 cm (cT1a) without risk factors. This study investigated the clinicopathologic characteristics of PTCs measuring ≤2.0 cm without cervical lymph node metastasis (cT1N0) by tumor size group to assess the feasibility of AS for PTCs between 1.0 cm and 1.5 cm (cT1b≤1.5).

Design

This study enrolled clinically T1N0 patients with preoperative ultrasonography information (n= 935) from a cohort of 1259 patients who underwent lobectomy and were finally diagnosed with PTC from June 2020 to March 2022.

Results

The cT1b≤1.5 group (n = 171; 18.3 %) exhibited more lymphatic invasion and occult central lymph node (LN) metastasis with a higher metastatic LN ratio than the cT1a group (n = 719; 76.9 %). However, among patients aged 55 years or older, there were no significant differences in occult central LN metastasis and metastatic LN ratio between the cT1a, cT1b≤1.5, and cT1b>1.5 groups. Multivariate regression analyses revealed that occult central LN metastasis was associated with age, sex, tumor size, extrathyroidal extension, and lymphatic invasion in patients under 55, while in those aged 55 or older, it was associated only with age and lymphatic invasion.

Conclusion

For PTC patients aged 55 years or older with cT1b≤1.5, AS could be a viable option due to the absence of a significant relationship between tumor size and occult central LN.

Open access
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.

Open access
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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Laura Croce Department of Internal Medicine and Therapeutics, University of Pavia, Pavia (PV), Italy
Istituti Clinici Scientifici Maugeri IRCCS, Unit of Endocrinology and Metabolism, Laboratory for Endocrine Disruptors, Pavia (PV), Italy

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Fausta Beneventi Department of Obstetrics and Gynecology, IRCCS Foundation Policlinico San Matteo, University of Pavia, Pavia (PV), Italy

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Federica Ripepi Department of Internal Medicine and Therapeutics, University of Pavia, Pavia (PV), Italy

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Irene De Maggio Department of Obstetrics and Gynecology, IRCCS Foundation Policlinico San Matteo, University of Pavia, Pavia (PV), Italy

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Alberto Malovini Istituti Clinici Scientifici Maugeri IRCCS, Laboratory of Informatics and Systems Engineering for Clinical Research, Pavia (PV), Italy

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Camilla Bellingeri Department of Obstetrics and Gynecology, IRCCS Foundation Policlinico San Matteo, University of Pavia, Pavia (PV), Italy

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Francesca Coperchini Department of Internal Medicine and Therapeutics, University of Pavia, Pavia (PV), Italy

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Marsida Teliti Department of Internal Medicine and Therapeutics, University of Pavia, Pavia (PV), Italy
Istituti Clinici Scientifici Maugeri IRCCS, Unit of Endocrinology and Metabolism, Laboratory for Endocrine Disruptors, Pavia (PV), Italy

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Mario Rotondi Department of Internal Medicine and Therapeutics, University of Pavia, Pavia (PV), Italy
Istituti Clinici Scientifici Maugeri IRCCS, Unit of Endocrinology and Metabolism, Laboratory for Endocrine Disruptors, Pavia (PV), Italy

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Arsenio Spinillo Department of Obstetrics and Gynecology, IRCCS Foundation Policlinico San Matteo, University of Pavia, Pavia (PV), Italy

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Flavia Magri Department of Internal Medicine and Therapeutics, University of Pavia, Pavia (PV), Italy
Istituti Clinici Scientifici Maugeri IRCCS, Unit of Endocrinology and Metabolism, Laboratory for Endocrine Disruptors, Pavia (PV), Italy

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Objective

Obesity is associated with increased thyroid-stimulating hormone (TSH) in non-pregnant subjects, but this phenomenon has not been fully characterized during pregnancy. Our aim was to evaluate the impact of BMI on first-trimester TSH in a wide cohort of pregnant women with negative anti-thyroperoxidase antibodies (AbTPO) and its implications on uterine artery pulsatility index (UtA-PI), a marker of early placentation.

Methods

The study included 2268 AbTPO-negative pregnant women at their first antenatal visit. Anamnestic data, BMI, TSH, anti-nuclear antibody (ANA) and extractable nuclear antigen (ENA) positivity and mean UtA-PI were collected.

Results

A total of 1693 women had normal weight, 435 were overweight and 140 were obese. Maternal age, ANA/ENA positivity, history of autoimmune diseases and familiar history of thyroid diseases were similar in the three groups. TSH was significantly higher in obese women (1.8 (IQR: 1.4–2.4) mU/L) when compared to normal weight (1.6 (IQR: 1.2–2.2) mU/L) and overweight (median: 1.6 (IQR: 1.2–2.2) mU/L) ones (P < 0.001). BMI was significantly related with the risk of having a TSH level ≥4 mU/L at logistic regression, independently from non-thyroid autoimmunity, smoking or familiar predisposition for thyroid diseases (OR: 1.125, 95% CI: 1.080–1.172, P < 0.001). A restricted cubic splines regression showed a non-linear relationship between BMI and TSH. Women with a TSH ≥4 mU/L had a higher UtA-PI, independently from BMI.

Conclusion

Overweight/obesity is significantly related with TSH serum levels in AbTPO-negative pregnant women, independently from the other risk factors for hypothyroidism during pregnancy. The increase of TSH levels could be clinically relevant, as suggested by its association with abnormal UtA-PI, a surrogate marker of abnormal placentation.

Open access
Marise Codeco de Andrade Barreto Department of Oncologic Endocrinology, Instituto Nacional de Câncer – INCA, Rio de Janeiro, RJ, Brazil
Department of Endocrinology, Universidade Federal do Rio de Janeiro – UFRJ, Faculdade de Medicina, Rio de Janeiro, RJ, Brazil

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Natalia Treistman Department of Endocrinology, Universidade Federal do Rio de Janeiro – UFRJ, Faculdade de Medicina, Rio de Janeiro, RJ, Brazil

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Lara Bessa Campelo Pinheiro Cavalcante Department of Endocrinology, Universidade Federal do Rio de Janeiro – UFRJ, Faculdade de Medicina, Rio de Janeiro, RJ, Brazil

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Daniel Bulzico Department of Oncologic Endocrinology, Instituto Nacional de Câncer – INCA, Rio de Janeiro, RJ, Brazil

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Fernanda Accioly de Andrade Department of Oncologic Endocrinology, Instituto Nacional de Câncer – INCA, Rio de Janeiro, RJ, Brazil

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Rossana Corbo Department of Oncologic Endocrinology, Instituto Nacional de Câncer – INCA, Rio de Janeiro, RJ, Brazil

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Paulo Alonso Garcia Alves Junior Department of Oncologic Endocrinology, Instituto Nacional de Câncer – INCA, Rio de Janeiro, RJ, Brazil
Department of Endocrinology, Universidade Federal do Rio de Janeiro – UFRJ, Faculdade de Medicina, Rio de Janeiro, RJ, Brazil

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Fernanda Vaisman Department of Oncologic Endocrinology, Instituto Nacional de Câncer – INCA, Rio de Janeiro, RJ, Brazil
Department of Endocrinology, Universidade Federal do Rio de Janeiro – UFRJ, Faculdade de Medicina, Rio de Janeiro, RJ, Brazil

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Introduction

Treatment of patients with pediatric differentiated thyroid cancer (DTC) often involves radioiodine (RAI), which is associated with increased risks of short- and long-term adverse outcomes. The impact of RAI treatment on the female reproductive system remains uncertain. Anti-Müllerian hormone (AMH) is a marker of ovarian reserve and is related to fertility.

Objective

The aim was to analyze the association between RAI and serum AMH level in women treated with RAI.

Methods

We evaluated women with pediatric DTC treated with RAI at the age of ≤19 years. Serum AMH was measured.

Results

The study included 47 patients with a mean age of 25.1 years (12.4–50.8) at AMH measurement and follow-up of 11.8 ± 8.4 years. The mean RAI administered was 235 mCi (30–1150). Sixteen (34%) received multiple RAI doses (471 ± 215 mCi). Mean AMH level was 2.49 ng/mL (0.01–7.81); the level was 1.57 ng/mL (0.01–7.81) after multiple RAI doses and 2.99 ng/mL (0.01–6.63) after a single RAI dose (P = 0.01). Patients who received a cumulative RAI lower than 200 mCi had higher AMH levels (2.23 ng/mL, 0.39–7.81) than those who received more (1.0 ng/mL, 0.01–6.63; P = 0.02). In patients with similar cumulative RAI activities, administration of multiple RAI doses was significantly and independently associated with AMH level lower than the reference range for age (HR: 5.9, 1.55–52.2, P = 0.014) after age adjustments.

Conclusion

Levels of AMH were lower after multiple RAI doses, especially after a cumulative RAI dose above 200 mCi. More studies are needed to clarify the impact of RAI on fertility considering its cumulative activity and treatment strategy.

Open access