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

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Min Soo Kim Department of Otorhinolaryngology-Head and Neck Surgery, Chungnam National University College of Medicine, Daejeon, Republic of Korea

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

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

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Objective

Active surveillance (AS) has been suggested as a management option for low-risk papillary thyroid microcarcinoma (PTMC). However, the currently proposed selection criteria for AS application do not consider various clinical factors. The purpose of this study was to analyze clinical factors related to recurrence that could be confirmed preoperatively in patients who underwent surgery for PTMC and to identify factors worth considering when deciding whether to apply AS.

Materials and methods

Data were collected from patients with PTMC who underwent surgical treatment at Chungnam National University Hospital. A retrospective cohort was established according to the presence or absence of recurrence during the follow-up period. In total, 2717 patients were enrolled, of whom 60 experienced recurrence. Various clinical factors that could be identified before surgery were analyzed.

Results

The relationship between various clinical factors that could be confirmed preoperatively and recurrence was confirmed through Cox regression analysis and Kaplan–Meier curve analysis. BRAF mutation and the tall cell variant were significantly more common in patients with recurrence. In patients aged 55 years or older, the risk of recurrence was lower than in younger patients, while the recurrence-free survival (RFS) rate was higher.

Conclusion

When choosing between surgical treatment or AS in PTMC patients, additional consideration of the patient’s clinical factors, such as age and BRAF mutation status, may be required in addition to the existing criteria.

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Sander Barnhoorn Department of Molecular Genetics, Erasmus Medical Center, Rotterdam, The Netherlands

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Marcel E Meima Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands

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Robin P Peeters Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands

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Veerle M Darras Laboratory of Comparative Endocrinology, Biology Department, KU Leuven, Leuven, Belgium

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Selmar Leeuwenburgh Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands

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Jan H J Hoeijmakers Department of Molecular Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Oncode Institute, Utrecht, The Netherlands
Institute for Genome Stability in Ageing and Disease, CECAD Research Centre, Cologne, Germany

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Wilbert P Vermeij Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Oncode Institute, Utrecht, The Netherlands

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W Edward Visser Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands

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Background

Thyroid hormone signaling is essential for development, metabolism, and response to stress but declines during aging, the cause of which is unknown. DNA damage accumulating with time is a main cause of aging, driving many age-related diseases. Previous studies in normal and premature aging mice, due to defective DNA repair, indicated reduced hepatic thyroid hormone signaling accompanied by decreased type 1 deiodinase (DIO1) and increased DIO3 activities. We investigated whether aging-related changes in deiodinase activity are driven by systemic signals or represent cell- or organ-autonomous changes.

Methods

We quantified liver and plasma thyroid hormone concentrations, deiodinase activities and expression of T3-responsive genes in mice with a global, liver-specific and for comparison brain-specific inactivation of Xpg, one of the endonucleases critically involved in multiple DNA repair pathways.

Results

Both in global and liver-specific Xpg knockout mice, hepatic DIO1 activity was decreased. Interestingly, hepatic DIO3 activity was increased in global, but not in liver-specific Xpg mutants. Selective Xpg deficiency and premature aging in the brain did not affect liver or systemic thyroid signaling. Concomitant with DIO1 inhibition, Xpg −/− and Alb-Xpg mice displayed reduced thyroid hormone-related gene expression changes, correlating with markers of liver damage and cellular senescence.

Conclusions

Our findings suggest that DIO1 activity during aging is predominantly modified in a tissue-autonomous manner driven by organ/cell-intrinsic accumulating DNA damage. The increase in hepatic DIO3 activity during aging largely depends on systemic signals, possibly reflecting the presence of circulating cells rather than activity in hepatocytes.

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Yun Jeong Lee Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Republic of Korea
Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea

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Young Hun Choi Department of Radiology, Seoul National University Hospital, Seoul, Korea

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Youn-Hee Lim Section of Environmental Health, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea
Environmental Health Center, Seoul National University College of Medicine, Seoul, Republic of Korea

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Bung-Nyun Kim Division of Children and Adolescent Psychiatry, Department of Psychiatry, Seoul National University Hospital, Seoul, Republic of Korea

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Johanna Inhyang Kim Department of Psychiatry, Hanyang University Medical Center, Seoul, Republic of Korea

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Yun-Chul Hong Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea
Environmental Health Center, Seoul National University College of Medicine, Seoul, Republic of Korea
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

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

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Choong Ho Shin Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Republic of Korea
Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea

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Sun Wook Cho Department of Internal medicine, Seoul National University Hospital, Seoul, Republic of Korea
Department of Internal medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

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Young Ah Lee Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Republic of Korea
Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea

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Objective

Adequate iodine intake is essential for growing children, and thyroid volume (Tvol) is considered as an indicator of iodine status. We investigated Tvol and goiter using ultrasonography (US) and their association with iodine status in 228 6-year-old children living in Korea.

Methods

Iodine status was assessed using urine iodine concentration (UIC) and categorized as deficient (<100 μg/L), adequate (100–299 μg/L), mild excess (300–499 μg/L), moderate excess (500–999 μg/L), and severe excess (≥1000 μg/L). Tvol was measured using US, and a goiter on the US (goiter-US) was defined as Tvol greater than 97th percentile value by age- and body surface area (BSA)-specific international references.

Results

The median Tvol was 2.4 mL, larger than the international reference value (1.6 mL). The age- and BSA-specific goiter-US rates were 25.9% (n = 59) and 34.6% (n = 79), respectively. The prevalence of excess iodine was 73.7% (n = 168). As iodine status increased from adequate to severe excess, the goiter-US rate significantly increased (P for trend <0.05). The moderate and severe iodine excess groups showed higher risk of goiter-US (adjusted odds ratio (aOR) = 3.1 (95% CI: 1.1–9.2) and aOR = 3.1 (95% CI: 1.2–8.3), respectively; age-specific criteria) than the iodine-adequate group.

Conclusions

Excess iodine was prevalent in Korean children, and their Tvol was higher than the international reference values. Goiter rate was associated with iodine excess, which significantly increased in the moderate and severe iodine excess groups. Further studies are warranted to define optimal iodine intake in children.

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S H S Pearce Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom

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L Persani Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy

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Emna Jelloul Endocrine Unit Centre Hospitalier Universitaire (CHU) Saint Pierre, Université Libre de Bruxelles (ULB), Rue Haute, Brussels, Belgium

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Georgiana Sitoris Endocrine Unit Centre Hospitalier Universitaire (CHU) Saint Pierre, Université Libre de Bruxelles (ULB), Rue Haute, Brussels, Belgium

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Flora Veltri Endocrine Unit Centre Hospitalier Universitaire (CHU) Saint Pierre, Université Libre de Bruxelles (ULB), Rue Haute, Brussels, Belgium

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Pierre Kleynen Endocrine Unit Centre Hospitalier Universitaire (CHU) Saint Pierre, Université Libre de Bruxelles (ULB), Rue Haute, Brussels, Belgium

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Serge Rozenberg Departement of Gynecology and Obstetrics, Centre Hospitalier Universitaire Saint Pierre, Université Libre de Bruxelles (ULB), Rue Haute, Brussels, Belgium

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Kris G Poppe Endocrine Unit Centre Hospitalier Universitaire (CHU) Saint Pierre, Université Libre de Bruxelles (ULB), Rue Haute, Brussels, Belgium

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Objective

The aim of the study was to investigate the impact of suppressed serum TSH levels (sTSH) during early pregnancy on maternal and neonatal outcomes.

Methods

In this single-centre, retrospective cohort study 1081 women were screened at 11.8 ± 2.4 weeks of pregnancy for TSH, free T4 (FT4) and TPOAb. Exclusion criteria were twin- and assisted- reproduction pregnancies, women with TSH levels >3.74 mIU/L, severe hyperthyroidism, treated for thyroid dysfunction before or after screening and gestational blood sampling <6 or >16 weeks of pregnancy. The prevalence of adverse pregnancy outcomes was compared between the study group sTSH (TSH: < 0.06 mIU/L; n = 36) and euthyroid controls (TSH: 0.06–3.74 mIU/L; n = 1045), and the impact of sTSH on pregnancy outcomes verified in logistic regression analyses.

Results

Median (IQR) serum TSH level in women with sTSH was 0.03 (0.03–0.03) vs 1.25 (0.81–1.82) mIU/L in controls and FT4 levels 18.0 (14.4–20.3) vs 14.2 (12.9–15.4) pmol/L; both P < 0.001. None of the women with sTSH had thyrotropin receptor antibodies. Compared with controls, the prevalence of TPOAb positivity (TAI) was comparable between groups (5.6% vs 6.6%; P = 0.803). The prevalence of maternal and neonatal pregnancy outcomes was comparable between the study and control group. The logistic regression analyses with corrections for TAI, FT4 and demographic parameters confirmed the absence of an association between sTSH, and the following outcomes: iron deficient anaemia (aORs (95% CI)): 1.41 (0.64-2.99); P = 0.385, gestational diabetes: 1.19 (0.44–2.88); P = 0.713, preterm birth: 1.57 (0.23–6.22);P = 0.574 and low Apgar-1′ score: 0.71 (0.11–2.67); P = 0.657.

Conclusions

Suppressed serum TSH levels during the first to early second trimester of pregnancy were not associated with altered maternal or neonatal outcomes.

Open access
Kamilla R Riis Department of Endocrinology, Odense University Hospital, Odense, Denmark
Department of Clinical Research, University of Southern Denmark, Odense, Denmark

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Camilla B Larsen Department of Endocrinology, Odense University Hospital, Odense, Denmark
Department of Clinical Research, University of Southern Denmark, Odense, Denmark

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Bjarke R Medici Department of Medicine, Copenhagen University Hospital – Herlev and Gentofte, Denmark

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Christian Z Jensen Department of Medicine, Copenhagen University Hospital – Herlev and Gentofte, Denmark

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Kristian H Winther Department of Endocrinology, Odense University Hospital, Odense, Denmark

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Emil L Larsen Department of Clinical Pharmacology, Bispebjerg-Frederiksberg Hospital, Copenhagen, Denmark

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Christina Ellervik Department of Laboratory Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, United States of America
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Data and Data Support, Region Zealand, Sorø, Denmark

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Jeppe L la Cour Department of Medicine, Copenhagen University Hospital – Herlev and Gentofte, Denmark

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Laszlo Hegedüs Department of Endocrinology, Odense University Hospital, Odense, Denmark
Department of Clinical Research, University of Southern Denmark, Odense, Denmark

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Thomas H Brix Department of Endocrinology, Odense University Hospital, Odense, Denmark

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Henrik E Poulsen Department of Endocrinology, Copenhagen University Hospital, Bispebjerg-Frederiksberg Hospital, Denmark
Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
Department of Cardiology, University Hospital Nordsjælland, Hillerød, Denmark

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Filip K Knop Department of Medicine, Copenhagen University Hospital – Herlev and Gentofte, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Herlev, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Birte Nygaard Department of Medicine, Copenhagen University Hospital – Herlev and Gentofte, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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

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Objective

Some studies suggest that hypothyroidism is associated with increased oxidative stress. Urinary excretion of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) represents whole-body RNA and DNA oxidation, respectively. These biomarkers have only been explored sparsely in patients with thyroid disorders.

Methods

In 45 Danish women with newly diagnosed hypothyroidism, we compared 8-oxoGuo and 8-oxodG before or shortly after initiating levothyroxine with the excretion rates at euthyroidism. We also compared the excretion of 8-oxoGuo and 8-oxodG in the patients after restored euthyroidism with 18 healthy control subjects.

Results

Compared with baseline, none of the biomarkers changed significantly in the patients after becoming euthyroid. The geometric mean of 8-oxoGuo was 1.63 (95% CI: 1.49–1.78) nmol/mmol creatinine at baseline and 1.67 nmol/mmol at euthyroidism (95% CI: 1.53–1.83) (P = 0.39), while that of 8-oxodG was 1.28 nmol/mmol creatinine at baseline (95% CI: 1.14–1.44) and 1.32 nmol/mmol at euthyroidism (95% CI: 1.18–1.48), respectively (P = 0.47). The relative mean differences were 0.97 (95% CI: 0.91–1.04) for 8-oxoGuo and 0.97 (95% CI: 0.88–1.06) for 8-oxodG. At baseline, multiple linear regression revealed a positive association between free thyroxine and both biomarkers (8-oxoGuo, P < 0.001; 8-oxodG, P = 0.04). Furthermore, 8-oxoGuo was positively associated with age (P = 0.04) and negatively associated with thyrotropin (P = 0.02). In the control group, the geometric mean of 8-oxoGuo was 1.23 nmol/mmol creatinine (95% CI: 1.07–1.42), while that of 8-oxodG was 1.04 nmol/mmol creatinine (95% CI: 0.88–1.23). Thus, compared with control subjects, euthyroid patients showed a significantly higher level of both 8-oxoGuo (P < 0.001) and 8-oxodG (P = 0.03).

Conclusion

In hypothyroid women, no significant effect of levothyroxine treatment on the oxidative stress biomarkers 8-oxoGuo and 8-oxodG could be demonstrated. However, the excretion of these biomarkers was significantly higher than in healthy controls.

Open access
Ziyu Wan Health Management Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China
Nursing Department, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Ying Li Health Management Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

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Xiaoqian Dong Xiangya School of Nursing, Central South University, Changsha, Hunan, China

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Yue Kang Xiangya School of Nursing, Central South University, Changsha, Hunan, China

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Juan Luo Xiangya School of Nursing, Central South University, Changsha, Hunan, China

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Jiangang Wang Health Management Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

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Pingting Yang Health Management Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

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Yaqin Wang Health Management Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

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Yinglong Duan Nursing Department, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Jianfei Xie Nursing Department, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Andy S K Cheng Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Hong Kong, China

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Introduction

Given the high prevalence of thyroid nodules and the potential for malignancy, it is imperative to understand the various factors that contribute to their development. This study aimed to explore the relationship between metabolic syndrome, lifestyle, and thyroid nodules in adult men in southern China.

Methods

This study enrolled a total of 183,990 subjects at a medical examination center in a general hospital in southern China between January 1, 2015, and December 31, 2020. Multivariate logistic regression analysis was utilized to evaluate the relationship between metabolic syndrome, lifestyle factors, and thyroid nodules. Furthermore, structural equation modeling elucidated the intricate relationships among these variables.

Results

The prevalence of thyroid nodules among Chinese adult males was 14.9%. Several factors were identified as risk factors for thyroid nodules, including advanced age, irregular meal time, smoking or quitting smoking, quitting drinking, heavy manual labor, hypertension, diabetes, dyslipidemia and centripetal obesity, and those belonging to ethnic minorities and drinking alcohol were found to be protective factors against thyroid nodules. Structural equation modeling highlighted metabolic syndrome's mediating role amidst lifestyle influences on thyroid nodules.

Conclusion

The prevalence of thyroid nodules in Chinese adult males is relatively moderate to low. The factors identified in this study can help clinicians identify high-risk patients and develop targeted screening strategies for the timely detection of thyroid nodules. However, further mechanistic research and longitudinal studies are necessary to explore the underlying causes and establish causal relationships.

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Lan Wu State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

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Salvatore Vaccarella International Agency for Research on Cancer (IARC/WHO), Lyon, France

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Chen-Yang Feng Information Technology Center, Sun Yat-sen University Cancer Center, Guangzhou, China

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Luigino Dal Maso Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy

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Yu Chen State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

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Wei-Wei Liu Department of Head and Neck, Sun Yat-sen University Cancer Center, Guangzhou, China

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Miao-Bian Liang State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

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Zike Zhang Department of Laboratory Medicine, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

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Jun Yang School of Public Health, Guangzhou Medical University, Guangzhou, China

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Su-Mei Cao State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

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Mengmeng Li State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

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Background

Incidence rates of papillary thyroid cancer (PTC) have increased rapidly, with incidentally detected cancers contributing a large proportion. We aimed to explore the impact of incidental detection on thyroid cancer-specific and competing mortality among PTC patients.

Methods

We conducted a retrospective cohort study of PTC patients at a cancer center in Guangzhou. Baseline information on detection route and other covariates were collected between 2010 and 2018, and death outcome was followed up for each patient. Cumulative incidence functions were used to estimate the mortality risk of thyroid cancer and competing risk. Cause-specific hazard models were then utilized to explore the association between detection routes and PTC-specific and competing mortality.

Results

Of the 2874 patients included, 2011 (70.0%) were detected incidentally, and the proportion increased from 36.9% in 2011 to 82.3% in 2018. During a median follow-up of 5.6 years, 42 deaths occurred, with 60% of them due to competing causes. The probability of competing mortality at 5 years in the non-incidental group and incidental group was 1.4% and 0.4%, respectively, and PTC-specific mortality in the non-incidental group and incidental group was 1.0% and 0.1%, respectively. After adjusting for covariates, the HRs of incidental detection were 0.13 (95% CI: 0.04–0.46; P = 0.01) and 0.47 (95% CI: 0.20–1.10; P = 0.10) on PTC-specific mortality and competing mortality, respectively.

Conclusions

Incidental detection is associated with a lower risk of PTC-specific and competing mortality. Under the context of increasing magnitude of overdiagnosis, incorporation of detection route in clinical decision-making might be helpful to identify patients who might benefit from more extensive or conservative therapeutic strategies.

Open access
Heleen I Jansen Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location Vrije Universiteit Amsterdam, Boelelaan, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands

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Marije van Haeringen Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Department of Computer Science, Vrije Universiteit, Boelelaan, Amsterdam, The Netherlands

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Marelle J Bouva Reference Laboratory Neonatal Screening, Center for Health protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands

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Wendy P J den Elzen Department of Laboratory Medicine, Laboratory Specialized Diagnostics & Research, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Public Health, Amsterdam, The Netherlands

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Eveline Bruinstroop Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Endocrinology and Metabolism, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands

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Catharina P B van der Ploeg TNO - Child Health, Sylviusweg, Leiden, The Netherlands

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A S Paul van Trotsenburg Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Paediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands

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Nitash Zwaveling-Soonawala Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Paediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands

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Annemieke C Heijboer Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location Vrije Universiteit Amsterdam, Boelelaan, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands

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Annet M Bosch Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Pediatrics, Division of Metabolic Disorders, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands

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Robert de Jonge Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Laboratory Medicine, Amsterdam UMC, Vrije Universiteit, Boelelaan, Amsterdam, The Netherlands
Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands

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Mark Hoogendoorn Department of Computer Science, Vrije Universiteit, Boelelaan, Amsterdam, The Netherlands

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Anita Boelen Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands

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Objective

Congenital hypothyroidism (CH) is an inborn thyroid hormone (TH) deficiency mostly caused by thyroidal (primary CH) or hypothalamic/pituitary (central CH) disturbances. Most CH newborn screening (NBS) programs are thyroid-stimulating-hormone (TSH) based, thereby only detecting primary CH. The Dutch NBS is based on measuring total thyroxine (T4) from dried blood spots, aiming to detect primary and central CH at the cost of more false-positive referrals (FPRs) (positive predictive value (PPV) of 21% in 2007–2017). An artificial PPV of 26% was yielded when using a machine learning-based model on the adjusted dataset described based on the Dutch CH NBS. Recently, amino acids (AAs) and acylcarnitines (ACs) have been shown to be associated with TH concentration. We therefore aimed to investigate whether AAs and ACs measured during NBS can contribute to better performance of the CH screening in the Netherlands by using a revised machine learning-based model.

Methods

Dutch NBS data between 2007 and 2017 (CH screening results, AAs and ACs) from 1079 FPRs, 515 newborns with primary (431) and central CH (84) and data from 1842 healthy controls were used. A random forest model including these data was developed.

Results

The random forest model with an artificial sensitivity of 100% yielded a PPV of 48% and AUROC of 0.99. Besides T4 and TSH, tyrosine, and succinylacetone were the main parameters contributing to the model’s performance.

Conclusions

The PPV improved significantly (26–48%) by adding several AAs and ACs to our machine learning-based model, suggesting that adding these parameters benefits the current algorithm.

Open access
Pi-Ling Chiang Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Thyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan

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Sheng-Dean Luo Thyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan
Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan

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Yen-Hsiang Chang Thyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan
Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan

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Chen-Kai Chou Thyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan

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Shun-Yu Chi Thyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan
Departments of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan

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Yi-Fan Chen Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Thyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan

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Wei-Che Lin Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Thyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan
Department of Radiology, Jen-Ai Hospital, Dali Branch, Taichung, Taiwan
School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung City, Taiwan

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Purpose

The purpose of this study was to evaluate the feasibility of radiofrequency ablation (RFA) for thyroid nodules with cytological atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS, Bethesda III).

Materials and methods

A total of 28 adults presenting with 30 initial Bethesda III nodules underwent thyroid RFA at a single medical center. Thyroid nodules with Bethesda IV or V according to the second aspiration were excluded. All RFA procedures were performed using the free-hand, ‘moving-shot’ technique under local anesthesia. Clinical features and demographics, RFA details, nodule volume reduction rate (VRR), and complications were analyzed.

Results

The mean age of patients was 47.6 years, 82.1% of whom were females. Mean nodule volumes at pre-RFA, and at 6 months and 12 months post-RFA were 7.92, 2.42, and 1.25 mL, respectively, with a VRR of 77.9% at 6 months, and 87.4% at 12 months. Post-RFA complications were noted in two patients, one with transient vocal cord palsy and another with isthmus minor rupture.

Conclusion

RFA may be another safe alternative except for active surveillance or surgical excision for AUS/FLUS nodules with low-suspicion Thyroid Imaging Reporting and Data System features for patients who are unsuitable or strongly refuse surgery. Long-term results remain uncertain, thus further follow-up study is necessary.

Open access