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Hsu-Hua Tseng Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

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Yen-Bo Lin Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Bei-Hu Branch, Taipei, Taiwan

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Kuan-Yu Lin Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliu City, Taiwan

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Chia-Hung Lin Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan

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Hung-Yuan Li Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

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Chia-Hsuin Chang Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

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Yi-Ching Tung Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

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Pei-Lung Chen Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan
Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan

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Chih-Yuan Wang Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

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Wei-Shiung Yang Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

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Shyang-Rong Shih Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Center of Anti-Aging and Health Consultation, National Taiwan University Hospital, Taipei, Taiwan

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Purpose

Autoimmune polyendocrine syndrome (APS) is a rare immune-endocrinopathy characterized by the failure of at least two endocrine organs. Clinical characteristics have mainly been described in the Western population. This study comprehensively analyzed the demographic and clinical manifestations of APS II and APS III in Taiwan.

Methods

Patients aged ≥20 years with a diagnosis of APS II or APS III in ten hospitals between 2001 and 2021 were enrolled. The clinical and serological characteristics of the patients were retrospectively reviewed.

Results

Among the 187 enrolled patients (45 men and 142 women); only seven (3.7%) had APS II, while the others had APS III. Fifty-five patients developed hyperthyroidism and 44 patients developed hypothyroidism. Men were diagnosed with APS at a younger age than women (16.8 vs 27.8 years old, P = 0.007). Most patients were initially diagnosed with type 1 diabetes mellitus. There was a positive correlation between age at diagnosis and the likelihood of developing thyroid dysfunction. For every year older patients were diagnosed with APS III, the risk of developing hyperthyroidism increased by 3.6% (P = 0.002), and the risk of developing hypothyroidism increased by 3.7% (P = 0.035). Positive anti-parietal cell antibodies (APCA) were associated with a higher risk of anemia in patients with APS III (P < 0.001).

Conclusion

This study provides the most comprehensive analysis of APS II and APS III in Asia. The percentage of patients with APS II was significantly lower than in the Western population. A second autoimmune endocrinopathy may develop several years after the first one. APCA examination is valuable when evaluating anemia in patients with APS.

Open access
Markus Eszlinger Department of Oncology and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Heritage Medical Research Building, Calgary, Alberta, Canada, and Institute of Pathology, University Hospital Halle, Halle, Germany

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Alexandra Stephenson Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Heritage Medical Research Building, Calgary, Alberta, Canada

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Shideh Mirhadi Program in Cell Biology, Hospital for Sick Children, and Department of Molecular Genetics, University of Toronto, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada

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Konrad Patyra Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland

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Michael F Moran Program in Cell Biology, Hospital for Sick Children, and Department of Molecular Genetics, University of Toronto, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada

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Moosa Khalil Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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Jukka Kero Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland
Department of Pediatrics, Turku University Hospital, Turku, Finland

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Ralf Paschke Department of Oncology and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Heritage Medical Research Building, Calgary, Alberta, Canada, and Institute of Pathology, University Hospital Halle, Halle, Germany
Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Heritage Medical Research Building, Calgary, Alberta, Canada
Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Department of Medicine, Cumming School of Medicine, University of Calgary, Heritage Medical Research Building, Calgary, Alberta, Canada

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Objective

Nonautoimmune hyperthyroidism (NAH) is rare and occurs due to a constitutively activating thyroid stimulating hormone receptor (TSHR) mutation. In contrast to other thyroid nodules, no further evaluation for malignancy is recommended for hot thyroid nodules. In the first model for NAH in mice nearly all homozygous mice had developed papillary thyroid cancer by 12 months of age.

Methods

To further evaluate these mice, whole exome sequencing and phosphoproteome analysis were employed in a further generation of mice to identify any other mutations potentially responsible and to identify the pathways involved in thyroid carcinoma development.

Results

Only three genes (Nrg1, Rrs1, Rasal2) were mutated in all mice examined, none of which were known primary drivers of papillary thyroid cancer development. Wild-type and homozygous TSHR D633H knockin mice showed distinct phosphoproteome profiles with an enrichment of altered phosphosites found in ERK/mitogen-activated protein kinase (MAPK) signaling. Most importantly, phosphosites with known downstream effects included BRAF p.S766, which forms an inhibitory site: a decrease of phosphorylation at this site suggests an increase in MEK/ERK pathway activation. The decreased phosphorylation at BRAF p.S766 would suggest decreased AMP-activated protein kinase (AMPK) signaling, which is supported by the decreased phosphorylation of STIM1 p.S257, a downstream AMPK target.

Conclusion

The modified phosphoproteome profile of the homozygous mice in combination with human literature suggests a potential signaling pathway from constitutive TSHR signaling and cAMP activation to the activation of ERK/MAPK signaling. This is the first time that a specific mechanism has been identified for a possible involvement of TSH signaling in thyroid carcinoma development.

Open access
Aglaia Kyrilli Department of Endocrinology, Hôpital Universitaire de Bruxelles (H.U.B.)– Hôpital Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, Brussels, Belgium

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Nunzia Tacelli Department of Radiology, Hôpital Universitaire de Bruxelles (H.U.B.)– Hôpital Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, Brussels, Belgium

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Lucia Russo Department of Medicine, DIMED, Internal Medicine 3, University of Padua, Via Giustiniani 2, 35128, Padova, Italy

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Laetitia Lebrun Department of Pathology, Hôpital Universitaire de Bruxelles (H.U.B.)– Hôpital Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, Brussels, Belgium

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Isabelle Salmon Department of Pathology, Hôpital Universitaire de Bruxelles (H.U.B.)– Hôpital Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, Brussels, Belgium

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Gilles Russ Thyroid and Endocrine Tumors, Institute of Endocrinology, Pitié Salpêtrière Hospital, Pierre et Marie Curie University, Paris, France

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Rodrigo Moreno-Reyes Department of Nuclear Medicine, Hôpital Universitaire de Bruxelles (H.U.B.)– Hôpital Erasme, Université Libre de Bruxelles (ULB), Route de Lennik, Brussels, Belgium

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Bernard Corvilain Department of Endocrinology, Hôpital Universitaire de Bruxelles (H.U.B.)– Hôpital Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, Brussels, Belgium

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Objectives

The aim was to evaluate the clinical, ultrasound (US) and, when indicated, the cytological and histological characteristics of autonomously functioning thyroid nodules (AFTN) in consecutive patients.

Methods

A prospective, single-centre study was conducted between March 2018 and September 2021. In total, 901 consecutive patients were referred for thyroid workup and of 67 AFTN were evaluated. All enrolled patients underwent 99mTcO4 scintigraphy, additional 123I scintigraphy only in case of normal serum TSH, evaluation of thyroid function, US examination using European Thyroid Imaging and Reporting Data System (EU-TIRADS), and US-guided fine needle aspiration (FNA) cytology when indicated. All indeterminate FNA samples were subjected to DNA sequencing analysis.

Results

More than half of the evaluated patients with AFTN were euthyroid; median serum TSH was 0.41 (IQR: 0.03–0.97) mU/L. The median AFTN size measured by US was 27.0 (IQR: 21.1–35.0) mm. 28.4% of AFTN were classified as EU-TIRADS score 3 and 71.6% as EU-TIRADS score 4, indicating that the majority of AFTN had intermediate risk for malignancy according to US. Out of the 47 AFTN subjected to cytological evaluation, 24 (51%) yielded indeterminate FNA results. DNA sequencing revealed pathogenic TSHR and GNAS mutations in 60% of cases. No malignancy was detected at final histology in surgically excised AFTN (n = 12).

Conclusions

Of the 67 AFTN evaluated in this study, 50% presented with normal serum TSH, 70% displayed ultrasound features suggesting an intermediate malignancy risk and 50% of the AFTN submitted to cytology yielded indeterminate results. No malignant AFTN was detected.

Open access
Lise Husted Department of Clinical Biochemistry, Viborg Regional Hospital, Viborg, Denmark

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Sidsel Rødgaard-Hansen Department of Clinical Biochemistry, Viborg Regional Hospital, Viborg, Denmark

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Maja Hjelm Lundgaard Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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Nanna Maria Uldall Torp Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

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Stine Linding Andersen Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

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Objective

The physiological adaptations during a normal pregnancy affect renal and thyroid function and levels of associated biochemical markers. An association between cystatin C (CysC), creatinine, and thyroid function has been considered in nonpregnant individuals but not in pregnant women specifically.

Methods

Cohort study within the North Denmark Region Pregnancy Cohort (2011–2015) with assessment of thyroid function and autoantibodies (ADVIA Centaur XPT, Siemens Healthineers) in serum residues from the early pregnancy. Consecutive samples (n = 1112) were selected for measurement of CysC and creatinine (Atellica CH 930, Siemens Healthineers), and results were linked to information in Danish nationwide registers for (i) establishment of pregnancy-specific reference intervals for CysC and creatinine and (ii) evaluation of the prevalence of maternal hypothyroidism in early pregnancy according to levels of CysC and creatinine.

Results

The established reference intervals (2.5–97.5 percentiles) differed by week of pregnancy (week 4–8, 9–11, 12–15) and were CysC: 0.58–0.92 mg/L; 0.54–0.91 mg/L; 0.52–0.86 mg/L; creatinine: 46.9–73.0 µmol/L; 42.0–68.4 µmol/L; 38.8–66.4 µmol/L. The prevalence of maternal autoimmune hypothyroidism in early pregnancy differed by the level of CysC and creatinine (<25th percentile; 25th–75th percentile; >75th percentile) and was for CysC 1.7%, 3.8%, 7.4% and for creatinine 2.5%, 4.1%, 7.1%.

Conclusions

Reference intervals for CysC and creatinine were dynamic in early pregnancy and decreased with increasing gestational age. Furthermore, higher levels of CysC and creatinine associated with a higher prevalence of maternal autoimmune hypothyroidism. Results encourage considerations on the underlying mechanisms for the association between markers of renal and thyroid function.

Open access
Hai-Yan Jia Department of Ultrasound, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China

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Juan Chen Department of Ultrasound, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, China

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Zi-Xin Zhai Department of Ultrasound, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China

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Wen-Wen Fan Department of Ultrasound, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China

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Si-Jie Yuan Department of Ultrasound, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China

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Qiong Liu Department of Ultrasound, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China

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Xiao-Hui Yan Department of Ultrasound, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China

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Qian-Qian Shen Department of Ultrasound, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China

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Li-Ping Liu Department of Ultrasound, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China

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Introduction

Thyroid metastasis from clear cell renal cell carcinoma (ccRCC) is relatively rare, so ultrasound doctors lack experience with the disease, which can easily lead to misdiagnosis. We describe three cases of thyroid metastasis from ccRCC detected 12, 8, and 7 years after nephrectomy.

Case presentation

The first patient, a 78-year-old woman, was admitted to our institution for hoarseness and progressive dyspnea. Ultrasonography revealed bilateral thyroid nodules and abnormal cervical lymph nodes. Fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) of the thyroid was nondiagnostic. The other two patients, a 54-year-old man and a 65-year-old man, were admitted to our institution for a goiter pressing on the trachea. In each case, ultrasonography revealed a partially cystic nodule of the left lobe of the thyroid gland. Histological examination of three patients after thyroidectomy showed thyroid metastasis from ccRCC.

Discussion/Conclusion

For patients with a history of ccRCC, long-term follow-up and routine thyroid ultrasonography should be performed. If a new thyroid nodule is found during the examination, metastases should be highly suspected. FNAB should be performed, even if benign ultrasound features seem to be in evidence. If the diagnosis of FNAB is incorrect and inconclusive, CNB should be performed.

Open access
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.

Open access
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.

Open access
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.

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