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Thyroid
Update from the 2022 World Health Organization Classification of Thyroid Tumors: A Standardized Diagnostic Approach
Chan Kwon Jung, Andrey Bychkov, Kennichi Kakudo
Endocrinol Metab. 2022;37(5):703-718.   Published online October 4, 2022
DOI: https://doi.org/10.3803/EnM.2022.1553
  • 13,343 View
  • 1,856 Download
  • 39 Web of Science
  • 53 Crossref
AbstractAbstract PDFPubReader   ePub   
The fifth edition of the World Health Organization (WHO) histologic classification of thyroid neoplasms released in 2022 includes newly recognized tumor types, subtypes, and a grading system. Follicular cell-derived neoplasms are categorized into three families (classes): benign tumors, low-risk neoplasms, and malignant neoplasms. The terms “follicular nodular disease” and “differentiated high-grade thyroid carcinoma” are introduced to account for multifocal hyperplastic/neoplastic lesions and differentiated thyroid carcinomas with high-grade features, respectively. The term “Hürthle cells” is replaced with “oncocytic cells.” Invasive encapsulated follicular and cribriform morular variants of papillary thyroid carcinoma (PTC) are now redefined as distinct tumor types, given their different genetic alterations and clinicopathologic characteristics from other PTC subtypes. The term “variant” to describe a subclass of tumor has been replaced with the term “subtype.” Instead, the term “variant” is reserved to describe genetic alterations. A histologic grading system based on the mitotic count, necrosis, and/or the Ki67 index is used to identify high-grade follicular-cell derived carcinomas and medullary thyroid carcinomas. The 2022 WHO classification introduces the following new categories: “salivary gland-type carcinomas of the thyroid” and “thyroid tumors of uncertain histogenesis.” This review summarizes the major changes in the 2022 WHO classification and their clinical relevance.

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Close layer
Thyroid
Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions
Laura Sabatino, Cristina Vassalle, Cristina Del Seppia, Giorgio Iervasi
Endocrinol Metab. 2021;36(5):952-964.   Published online October 21, 2021
DOI: https://doi.org/10.3803/EnM.2021.1198
  • 6,230 View
  • 250 Download
  • 29 Web of Science
  • 43 Crossref
AbstractAbstract PDFPubReader   ePub   
Thyroid hormone (TH) signaling is strictly regulated by iodothyronine deiodinase activity, which both preserves the circulating levels of the biologically active triiodothyronine (T3) and regulates TH homeostasis at the local level, in a cell- and time-dependent manner. Three deiodinases have been identified—namely iodothyronine deiodinase 1 (DIO1), DIO2, and DIO3—that differ in their catalytic properties and tissue distribution. The deiodinases represent a dynamic system that changes in the different stages of life according to their functions and roles in various cell types and tissues. Deiodinase activity at the tissue level permits cell-targeted fine regulation of TH homeostasis, mediating the activation (DIO1 and DIO2) and inactivation (DIO3) of THs. Deiodinase homeostasis is the driving force that leads T3-target cells towards customized TH signaling, which takes into account both the hormonal circulating levels and the tissue-specific response. This review analyzes the complex role of deiodinases in physiological and pathological contexts, exploring new challenges and opportunities deriving from a deeper knowledge of the dynamics underlying their roles and functions.

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Close layer
Original Article
Thyroid
Insights from a Prospective Follow-up of Thyroid Function and Autoimmunity among COVID-19 Survivors
David Tak Wai Lui, Chi Ho Lee, Wing Sun Chow, Alan Chun Hong Lee, Anthony Raymond Tam, Carol Ho Yi Fong, Chun Yiu Law, Eunice Ka Hong Leung, Kelvin Kai Wang To, Kathryn Choon Beng Tan, Yu Cho Woo, Ching Wan Lam, Ivan Fan Ngai Hung, Karen Siu Ling Lam
Endocrinol Metab. 2021;36(3):582-589.   Published online June 8, 2021
DOI: https://doi.org/10.3803/EnM.2021.983
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  • 31 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Background
The occurrence of Graves’ disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors.
Methods
We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months.
Results
In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer.
Conclusion
Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

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Close layer
Review Article
Thyroid
Current Guidelines for Management of Medullary Thyroid Carcinoma
Mijin Kim, Bo Hyun Kim
Endocrinol Metab. 2021;36(3):514-524.   Published online June 22, 2021
DOI: https://doi.org/10.3803/EnM.2021.1082
  • 16,480 View
  • 1,580 Download
  • 26 Web of Science
  • 27 Crossref
AbstractAbstract PDFPubReader   ePub   
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from the parafollicular cells. The diagnostic and therapeutic strategies for the condition are different from those used for well-differentiated thyroid cancer. Since the 2015 American Thyroid Association guidelines for the diagnosis and treatment of MTC, the latest, including the National Comprehensive Cancer Network and European Association for Medical Oncology guidelines have been updated to reflect several recent advances in the management of MTC. Advances in molecular diagnosis and postoperative risk stratification systems have led to individualized treatment and follow-up strategies. Multi-kinase inhibitors, such as vandetanib and cabozantinib, can prolong disease progression-free survival with favorable adverse effects. In addition, potent selective rearranged during transfection (RET) inhibitors (selpercatinib and pralsetinib) have shown a promising efficacy in recent clinical trials. This review summarizes the management of MTC in recent guidelines focused on sporadic MTC.

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Original Article
Clinical Study
Characteristics of Immune-Related Thyroid Adverse Events in Patients Treated with PD-1/PD-L1 Inhibitors
Jee Hee Yoon, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang
Endocrinol Metab. 2021;36(2):413-423.   Published online April 6, 2021
DOI: https://doi.org/10.3803/EnM.2020.906
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  • 211 Download
  • 19 Web of Science
  • 20 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Thyroid immune-related adverse events (IRAEs) have been reported in patients treated with programmed cell death protein-1 (PD-1) and programmed cell death protein-ligand 1 (PD-L1) inhibitors. We investigated the incidence and clinical course of PD-1/PD-L1 inhibitor-induced thyroid IRAEs, and identified predictable clinical risk factors of thyroid IRAEs, in particular, overt hypothyroidism (OH).
Methods
We retrospectively reviewed the medical records of 325 cancer patients receiving PD-1/PD-L1 inhibitor in a tertiary referral center.
Results
A total of 50.5% (164/325) of patients experienced at least one abnormal thyroid function following PD-1/PD-L1 inhibitor. Eighty-four patients (51.2%) of them recovered to normal thyroid function during follow-up. In overall population, 25 patients (7.7%) required thyroid hormone replacement therapy due to PD-1/PD-L1 inhibitor-induced OH. Patients who progressed to OH showed significantly higher baseline thyroid stimulating hormone level and longer duration of PD-1/PD-L1 inhibitor therapy than those without thyroid dysfunction or OH (both P<0.001). Median time interval to the development of OH was 3 months after the therapy. OH was significantly associated with positive anti-thyroid peroxidase antibody at baseline and anti-thyroglobulin antibody during the therapy than those without thyroid dysfunction or OH (P=0.015 and P=0.005, respectively). We observed no patients with OH who were able to stop levothyroxine replacement after the cessation of PD-1/PD-L1 inhibitor therapy.
Conclusion
PD-1/PD-L1 inhibitor-induced thyroid dysfunctions are considerably reversible; however, OH is irreversible requiring levothyroxine replacement even after stopping the therapy. Positive thyroid autoantibodies may predict the progression to OH.

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Review Article
Thyroid
Subclinical Hypothyroidism: Prevalence, Health Impact, and Treatment Landscape
Won Sang Yoo, Hyun Kyung Chung
Endocrinol Metab. 2021;36(3):500-513.   Published online June 18, 2021
DOI: https://doi.org/10.3803/EnM.2021.1066
  • 8,334 View
  • 526 Download
  • 16 Web of Science
  • 17 Crossref
AbstractAbstract PDFPubReader   ePub   
Subclinical hypothyroidism (sHypo) is defined as normal serum free thyroid hormone levels coexisting with elevated serum thyroid-stimulating hormone (TSH) levels. sHypo is a common condition observed in clinical practice with several unique features. Its diagnosis should be based on an understanding of geographic and demographic differences in biochemical criteria versus a global reference range for TSH that is based on the 95% confidence interval of a healthy population. During the differential diagnosis, it is important to remember that a considerable proportion of sHypo cases are transient and reversible in nature; the focus is better placed on persistent or progressive forms, which mainly result from chronic autoimmune thyroiditis. Despite significant evidence documenting the health impacts of sHypo, the effects of levothyroxine treatment (LT4-Tx) in patients with sHypo remains controversial, especially in patients with grade 1 sHypo and older adults. Existing evidence suggests that it is reasonable to refrain from immediate LT4-Tx in most patients if they are closely monitored, except in women who are pregnant or in progressive cases. Future research is needed to further characterize the risks and benefits of LT4-Tx in different patient cohorts.

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Close layer
Original Articles
Thyroid
Thyroid Hormone Profile and Its Prognostic Impact on the Coronavirus Disease 2019 in Korean Patients
Jiyeon Ahn, Min Kyung Lee, Jae Hyuk Lee, Seo Young Sohn
Endocrinol Metab. 2021;36(4):769-777.   Published online August 27, 2021
DOI: https://doi.org/10.3803/EnM.2021.1109
  • 4,107 View
  • 183 Download
  • 16 Web of Science
  • 17 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Data on the association between coronavirus disease 2019 (COVID-19) and thyroid have been reported, including overt thyrotoxicosis and suppression of thyroid function. We aimed to evaluate the thyroid hormone profile and its association with the prognosis of COVID-19 in Korean patients.
Methods
The clinical data of 119 patients with COVID-19, admitted in the Myongji Hospital, Goyang, South Korea, were retrospectively evaluated. The thyroid hormone profiles were analyzed and compared based on disease severity (non-severe disease vs. severe to critical disease). Clinical outcomes were analyzed according to the tertiles of thyroid hormones.
Results
Of the 119 patients, 76 (63.9%) were euthyroid, and none presented with overt thyroid dysfunction. Non-thyroidal illness syndrome was the most common manifestation (18.5%), followed by subclinical thyrotoxicosis (14.3%) among patients with thyroid dysfunction. Thyroid stimulating hormone (TSH) and triiodothyronine (T3) levels were significantly lower in patients with severe to critical disease than in those with non-severe disease (P<0.05). Patients in the lowest T3 tertile (<0.77 ng/mL) had higher rates of mechanical ventilation, intensive care unit admission, and death than those in the middle and highest (>1.00 ng/mL) T3 tertiles (P<0.05). COVID-19 patients in the lowest T3 tertile were independently associated with mortality (hazard ratio, 5.27; 95% confidence interval, 1.09 to 25.32; P=0.038) compared with those in the highest T3 tertile.
Conclusion
Thyroid dysfunction is common in COVID-19 patients. Changes in serum TSH and T3 levels may be important markers of disease severity in COVID-19. Decreased T3 levels may have a prognostic significance in COVID-19 related outcome.

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Close layer
Clinical Study
Efficacy of Ethanol Ablation for Benign Thyroid Cysts and Predominantly Cystic Nodules: A Systematic Review and Meta-Analysis
Cheng-Chun Yang, Yung Hsu, Jyun-Yan Liou
Endocrinol Metab. 2021;36(1):81-95.   Published online February 24, 2021
DOI: https://doi.org/10.3803/EnM.2020.833
  • 5,527 View
  • 209 Download
  • 10 Web of Science
  • 15 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Ultrasound-guided minimally invasive procedures are widely used to treat thyroid diseases. The objective of this study was to assess the efficacy and safety of ethanol ablation (EA) in comparison with other non-surgical options in the treatment of benign thyroid cystic nodules.
Methods
We conducted a systematic search of studies on EA for thyroid cystic nodules, mainly in the Ovid-MEDLINE and Embase, Web of Science, and Cochrane databases. The standardized mean difference (SMD) of the volume reduction ratio (VRR) after EA versus other non-surgical treatments comprised the primary outcome, whereas the odds ratio (OR) of therapeutic success rates between the two groups comprised the secondary outcome.
Results
The meta-analysis included 19 studies (four randomized controlled trials and 15 non-randomized studies) with 1,514 participants. The cumulative VRR of EA was 83.908% (95% confidence interval [CI], 79.358% to 88.457%). EA had a significantly higher pooled VRR (SMD, 0.381; 95% CI, 0.028 to 0.734; P=0.030), but not a significantly higher pooled therapeutic success rate (OR, 0.867; 95% CI, 0.132 to 5.689; P=0.880), than other forms of non-surgical management including radiofrequency ablation (RFA), polidocanol sclerotherapy, and simple aspiration with or without saline flush. However, the VRR and therapeutic success rate were not significantly different between EA and RFA. Major complications were recorded only in six patients (0.53%) with self-limiting dysphonia.
Conclusion
The role of EA as the first-line treatment for benign thyroid cysts and predominantly cystic nodules is supported by its high effectiveness and good safety profile compared to other currently available non-surgical options.

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    Gabrielle K. Steinl, Latoya A. Stewart, Catherine McManus, James A. Lee, Jennifer H. Kuo
    The American Journal of Surgery.2022; 224(1): 408.     CrossRef
  • Minimally-invasive treatments for benign thyroid nodules: recommendations for information to patients and referring physicians by the Italian Minimally-Invasive Treatments of the Thyroid group
    Giovanni Mauri, Stella Bernardi, Andrea Palermo, Roberto Cesareo, Enrico Papini, Luigi Solbiati, Daniele Barbaro, Salvatore Monti, Maurilio Deandrea, Laura Fugazzola, Giovanni Gambelunghe, Roberto Negro, Stefano Spiezia, Fulvio Stacul, Luca Maria Sconfien
    Endocrine.2022; 76(1): 1.     CrossRef
  • Image-Guided Percutaneous Ablation for Primary and Metastatic Tumors
    Arian Mansur, Tushar Garg, Apurva Shrigiriwar, Vahid Etezadi, Christos Georgiades, Peiman Habibollahi, Timothy C. Huber, Juan C. Camacho, Sherif G. Nour, Alan Alper Sag, John David Prologo, Nariman Nezami
    Diagnostics.2022; 12(6): 1300.     CrossRef
  • Approach to FNA of Thyroid Gland Cysts
    Esther Diana Rossi, Pietro Tralongo, Vincenzo Fiorentino, Mariangela Curatolo, Carmine Bruno, Carmen De Crea, Marco Raffaelli, Alfredo Pontecorvi, Luigi Maria Larocca
    Advances in Anatomic Pathology.2022; 29(6): 358.     CrossRef
Close layer
Clinical Study
Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma
Min Ji Jeon, Yea Eun Kang, Jae Hoon Moon, Dong Jun Lim, Chang Yoon Lee, Yong Sang Lee, Sun Wook Kim, Min-Hee Kim, Bo Hyun Kim, Ho-Cheol Kang, Minho Shong, Sun Wook Cho, Won Bae Kim
Endocrinol Metab. 2021;36(2):359-364.   Published online March 23, 2021
DOI: https://doi.org/10.3803/EnM.2020.890
Correction in: Endocrinol Metab 2022;37(1):181
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AbstractAbstract PDFPubReader   ePub   
Background
A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study.
Methods
Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases.
Conclusion
KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

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  • Thyroid‐Stimulating Hormone, Age, and Tumor Size are Risk Factors for Progression During Active Surveillance of Low‐Risk Papillary Thyroid Microcarcinoma in Adults
    Yasuhiro Ito, Akira Miyauchi, Makoto Fujishima, Takuya Noda, Tsutomu Sano, Takahiro Sasaki, Taketoshi Kishi, Tomohiko Nakamura
    World Journal of Surgery.2023; 47(2): 392.     CrossRef
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    Mitsuyoshi Hirokawa, Manon Auger, Chan Kwon Jung, Fabiano Mesquita Callegari
    Cancer Cytopathology.2023; 131(7): 415.     CrossRef
  • To Screen or Not to Screen?
    Do Joon Park
    Endocrinology and Metabolism.2023; 38(1): 69.     CrossRef
  • Lower Thyroid Cancer Mortality in Patients Detected by Screening: A Meta-Analysis
    Shinje Moon, Young Shin Song, Kyong Yeun Jung, Eun Kyung Lee, Young Joo Park
    Endocrinology and Metabolism.2023; 38(1): 93.     CrossRef
  • Long-Term Outcomes of Active Surveillance and Immediate Surgery for Adult Patients with Low-Risk Papillary Thyroid Microcarcinoma: 30-Year Experience
    Akira Miyauchi, Yasuhiro Ito, Makoto Fujishima, Akihiro Miya, Naoyoshi Onoda, Minoru Kihara, Takuya Higashiyama, Hiroo Masuoka, Shiori Kawano, Takahiro Sasaki, Mitsushige Nishikawa, Shuji Fukata, Takashi Akamizu, Mitsuru Ito, Eijun Nishihara, Mako Hisakad
    Thyroid®.2023; 33(7): 817.     CrossRef
  • Active Surveillance Outcomes of Patients with Low-Risk Papillary Thyroid Microcarcinoma According to Levothyroxine Treatment Status
    Masashi Yamamoto, Akira Miyauchi, Yasuhiro Ito, Makoto Fujishima, Takahiro Sasaki, Takumi Kudo
    Thyroid®.2023; 33(10): 1182.     CrossRef
  • Cost-Effectiveness of Active Surveillance Compared to Early Surgery of Small Papillary Thyroid Cancer: A Retrospective Study on a Korean Population
    Han-Sang Baek, Jeonghoon Ha, Kwangsoon Kim, Jaseong Bae, Jeong Soo Kim, Sungju Kim, Dong-Jun Lim, Chulmin Kim
    Journal of Korean Medical Science.2023;[Epub]     CrossRef
  • Optimal Cutoff Values of the Contact Angle of Tumor on Sonography System for Predicting Extrathyroidal Extension of Papillary Thyroid Carcinoma by Tumor Location
    Ik Beom Shin, Do Hoon Koo, Dong Sik Bae
    Clinical Medicine Insights: Oncology.2023;[Epub]     CrossRef
  • Thermal ablation for papillary thyroid microcarcinoma located in the isthmus: a study with 3 years of follow-up
    Lin Zheng, Fang-yi Liu, Jie Yu, Zhi-gang Cheng, Xiao-ling Yu, Xiao-cong Dong, Zhi-yu Han, Ping Liang
    Future Oncology.2022; 18(4): 471.     CrossRef
  • Trends in the Management of Localized Papillary Thyroid Carcinoma in the United States (2000–2018)
    Elisa Pasqual, Julie Ann Sosa, Yingxi Chen, Sara J. Schonfeld, Amy Berrington de González, Cari M. Kitahara
    Thyroid.2022; 32(4): 397.     CrossRef
  • Management of Low-Risk Thyroid Cancers: Is Active Surveillance a Valid Option? A Systematic Review of the Literature
    Renato Patrone, Nunzio Velotti, Stefania Masone, Alessandra Conzo, Luigi Flagiello, Chiara Cacciatore, Marco Filardo, Vincenza Granata, Francesco Izzo, Domenico Testa, Stefano Avenia, Alessandro Sanguinetti, Andrea Polistena, Giovanni Conzo
    Journal of Clinical Medicine.2021; 10(16): 3569.     CrossRef
  • Cost-Effectiveness Analysis of Active Surveillance Compared to Early Surgery in Small Papillary Thyroid Cancer: A Systemic Review
    Han-sang Baek, Chai-ho Jeong, Jeonghoon Ha, Ja-Seong Bae, Jeong-soo Kim, Dong-Jun Lim, Chul-Min Kim
    Cancer Management and Research.2021; Volume 13: 6721.     CrossRef
  • Active Surveillance as an Effective Management Option for Low-Risk Papillary Thyroid Microcarcinoma
    Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
    Endocrinology and Metabolism.2021; 36(4): 717.     CrossRef
Close layer
Clinical Study
Lactate Dehydrogenase A as a Potential New Biomarker for Thyroid Cancer
Eun Jeong Ban, Daham Kim, Jin Kyong Kim, Sang-Wook Kang, Jandee Lee, Jong Ju Jeong, Kee-Hyun Nam, Woong Youn Chung, Kunhong Kim
Endocrinol Metab. 2021;36(1):96-105.   Published online February 24, 2021
DOI: https://doi.org/10.3803/EnM.2020.819
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker.
Methods
LDHA expression was examined in 83 PTC tissue specimens by immunohistochemistry. Human thyroid cell lines were genetically manipulated to overexpress BRAFV600E or were treated with a BRAF-specific short hairpin RNA (shBRAF), whose effects on LDHA expression were evaluated by Western blotting. Data from 465 PTC patients were obtained from The Cancer Genome Atlas (TCGA) database and analyzed to validate the in vitro results.
Results
LDHA was aberrantly overexpressed in PTC. Intense immunostaining for LDHA was observed in PTC specimens carrying mutated BRAF, whereas the intensity was less in wild-type BRAF samples. Overexpression of BRAFV600E resulted in LDHA upregulation, whereas treatment with shBRAF downregulated LDHA in human thyroid cell lines. Furthermore, LDHA mRNA expression was significantly elevated and associated with BRAFV600E expression in thyroid cancer tissues from TCGA database. Additionally, LDHA overexpression was found to be correlated with aggressive clinical features of PTC, such as lymph node metastases and advanced tumor stages.
Conclusion
LDHA overexpression is associated with the BRAFV600E mutation and an aggressive PTC behavior. Therefore, LDHA may serve as a biomarker and therapeutic target in PTC.

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    Hongguo Xie, Xiaopeng Lu
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    Sai-li Duan, Min Wu, Zhe-Jia Zhang, Shi Chang
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    Hui-feng Wu, Hao Liu, Zhe-wei Zhang, Ji-min Chen
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    Jaime Eduardo Pachón Suárez, Marcela C. Salazar, Victor Z. Rizo
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    Sang-Hyeon Ju, Seong Eun Lee, Yea Eun Kang, Minho Shong
    Endocrinology and Metabolism.2022; 37(1): 53.     CrossRef
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    Taravat Khodaei, Sahil Inamdar, Abhirami P. Suresh, Abhinav P. Acharya
    Advanced Drug Delivery Reviews.2022; 184: 114242.     CrossRef
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    Shengnan Fan, Xiaoqing Li, Fanghui Ma, Minghui Yang, Juan Su, Xiang Chen
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    Nan Huo, Rui Cong, Zhi-jia Sun, Wen-chao Li, Xiang Zhu, Chun-yuan Xue, Zhao Chen, Lu-yuan Ma, Zhong Chu, Yu-chen Han, Xiao-feng Kang, Song-hao Jia, Nan Du, Lei Kang, Xiao-jie Xu
    Cell Death & Disease.2021;[Epub]     CrossRef
Close layer
Review Article
Thyroid
Thyroid Function across the Lifespan: Do Age-Related Changes Matter?
John P. Walsh
Endocrinol Metab. 2022;37(2):208-219.   Published online April 14, 2022
DOI: https://doi.org/10.3803/EnM.2022.1463
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AbstractAbstract PDFPubReader   ePub   
Circulating concentrations of thyrotropin (TSH) and thyroxine (T4) are tightly regulated. Each individual has setpoints for TSH and free T4 which are genetically determined, and subject to environmental and epigenetic influence. Pituitary-thyroid axis setpoints are probably established in utero, with maturation of thyroid function continuing until late gestation. From neonatal life (characterized by a surge of TSH and T4 secretion) through childhood and adolescence (when free triiodothyronine levels are higher than in adults), thyroid function tests display complex, dynamic patterns which are sexually dimorphic. In later life, TSH increases with age in healthy older adults without an accompanying fall in free T4, indicating alteration in TSH setpoint. In view of this, and evidence that mild subclinical hypothyroidism in older people has no health impact, a strong case can be made for implementation of age-related TSH reference ranges in adults, as is routine in children.

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    Rosalie B. T. M. Sterenborg, Inga Steinbrenner, Yong Li, Melissa N. Bujnis, Tatsuhiko Naito, Eirini Marouli, Tessel E. Galesloot, Oladapo Babajide, Laura Andreasen, Arne Astrup, Bjørn Olav Åsvold, Stefania Bandinelli, Marian Beekman, John P. Beilby, Jette
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    Nicole Lafontaine, Scott G Wilson, John P Walsh
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    Dongjin Lee, Moon Ahn
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    Hua Dong, Wenjie Zhou, Xingxu Yan, Huan Zhao, Honggang Zhao, Yan Jiao, Guijiang Sun, Yubo Li, Zuncheng Zhang
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    Hernando Vargas-Uricoechea, Valentina Agredo-Delgado, Hernando David Vargas-Sierra, María V. Pinzón-Fernández
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    Tessa A Mulder, Purdey J Campbell, Peter N Taylor, Robin P Peeters, Scott G Wilson, Marco Medici, Colin Dayan, Vincent V W Jaddoe, John P Walsh, Nicholas G Martin, Henning Tiemeier, Tim I M Korevaar
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Close layer
Original Articles
Endocrine Research
DEHP Down-Regulates Tshr Gene Expression in Rat Thyroid Tissues and FRTL-5 Rat Thyrocytes: A Potential Mechanism of Thyroid Disruption
Min Joo Kim, Hwan Hee Kim, Young Shin Song, Ok-Hee Kim, Kyungho Choi, Sujin Kim, Byung-Chul Oh, Young Joo Park
Endocrinol Metab. 2021;36(2):447-454.   Published online March 31, 2021
DOI: https://doi.org/10.3803/EnM.2020.920
  • 4,740 View
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  • 11 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Di-2-ethylhexyl phthalate (DEHP) is known to disrupt thyroid hormonal status. However, the underlying molecular mechanism of this disruption is unclear. Therefore, we investigated the direct effects of DEHP on the thyroid gland.
Methods
DEHP (vehicle, 50 mg/kg, and 500 mg/kg) was administered to Sprague-Dawley rats for 2 weeks. The expression of the thyroid hormone synthesis pathway in rat thyroid tissues was analyzed through RNA sequencing analysis, quantitative reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemical (IHC) staining. DEHP was treated to FRTL-5 rat thyroid cells, and an RT-PCR analysis was performed. A reporter gene assay containing the promoter of thyroid stimulating hormone receptor (TSHR) in Nthy-ori 3-1 human thyroid cells was constructed, and luciferase activity was determined.
Results
After DEHP treatment, the free thyroxine (T4) and total T4 levels in rats significantly decreased. RNA sequencing analysis of rat thyroid tissues showed little difference between vehicle and DEHP groups. In the RT-PCR analysis, Tshr expression was significantly lower in both DEHP groups (50 and 500 mg/kg) compared to that in the vehicle group, and IHC staining showed that TSHR expression in the 50 mg/kg DEHP group significantly decreased. DEHP treatment to FRTL-5 cells significantly down-regulated Tshr expression. DEHP treatment also reduced luciferase activity in a reporter gene assay for TSHR.
Conclusion
Although overall genetic changes in the thyroid hormone synthesis pathway are not clear, DEHP exposure could significantly down-regulate Tshr expression in thyroid glands. Down-regulation of Tshr gene appears to be one of potential mechanisms of thyroid disruption by DEHP exposure.

Citations

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  • ARTS is essential for di-2-ethylhexyl phthalate (DEHP)-induced apoptosis of mouse Leydig cells
    Yue Li, Linlin Xu, Chaoju Hao, Si Yang, Jinglei Wang, Jiaxiang Chen
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  • Thyroid dysfunction caused by exposure to environmental endocrine disruptors and the underlying mechanism: A review
    Jie He, Jie Xu, Mucong Zheng, Kai Pan, Lilin Yang, Lina Ma, Chuyang Wang, Jie Yu
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  • Intrauterine exposure to di(2-ethylhexyl) phthalate (DEHP) disrupts the function of the hypothalamus-pituitary-thyroid axis of the F1 rats during adult life
    Érica Kássia Sousa-Vidal, Guilherme Henrique, Renata Elen Costa da Silva, Caroline Serrano-Nascimento
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
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    Jingyi Xiao, Yujie Sha, Yuwen Huang, Kunling Long, Huan Wu, Yan Mo, Qiyuan Yang, Shengkun Dong, Qiang Zeng, Xiao Wei
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    Yuyao Yang, Xiaoyue Bai, Juan Lu, Ronghao Zou, Rui Ding, Xiaohui Hua
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    Marta Nazzari, Mírian Romitti, Duncan Hauser, Daniel J. Carvalho, Stefan Giselbrecht, Lorenzo Moroni, Sabine Costagliola, Florian Caiment
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Close layer
Thyroid
Association between Iodine Intake, Thyroid Function, and Papillary Thyroid Cancer: A Case-Control Study
Kyungsik Kim, Sun Wook Cho, Young Joo Park, Kyu Eun Lee, Dong-Wook Lee, Sue K. Park
Endocrinol Metab. 2021;36(4):790-799.   Published online August 11, 2021
DOI: https://doi.org/10.3803/EnM.2021.1034
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study aimed to assess the effects of iodine intake, thyroid function, and their combined effect on the risk of papillary thyroid cancer (PTC) and papillary thyroid microcarcinoma (PTMC).
Methods
A case-control study was conducted including 500 community-based controls who had undergone a health check-up, and 446 overall PTC cases (209 PTC and 237 PTMC) from the Thyroid Cancer Longitudinal Study. Urinary iodine concentration (UIC), was used as an indicator of iodine intake, and serum for thyroid function. The risk of PTC and PTMC was estimated using unconditional logistic regression.
Results
Excessive iodine intake (UIC ≥220 μg/gCr) was associated with both PTC (odds ratio [OR], 18.13 95% confidence interval [CI], 8.87 to 37.04) and PTMC (OR, 8.02; 95% CI, 4.64 to 13.87), compared to adequate iodine intake (UIC, 85 to 219 μg/gCr). Free thyroxine (T4) levels ≥1.25 ng/dL were associated with PTC (OR, 1.97; 95% CI, 1.36 to 2.87) and PTMC (OR, 2.98; 95% CI, 2.01 to 4.41), compared to free T4 levels of 0.7 to 1.24 ng/dL. Individuals with excessive iodine intake and high free T4 levels had a greatly increased OR of PTC (OR, 43.48; 95% CI, 12.63 to 149.62), and PTMC (OR, 26.96; 95% CI, 10.26 to 70.89), compared to individuals with adequate iodine intake and low free T4 levels.
Conclusion
Excessive iodine intake using creatinine-adjusted UIC and high free T4 levels may have a synergistic effect on PTC and PTMC. Considering both iodine intake and thyroid function is important to assess PTC and PTMC risk.

Citations

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  • Association between urinary iodine concentration and the risk of papillary thyroid cancer by sex and age: a case–control study
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    Vladimir Zaichick
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    Xueqi Zhang, Fan Zhang, Qiuxian Li, Chuyao Feng, Weiping Teng
    Frontiers in Nutrition.2022;[Epub]     CrossRef
  • The relationship between urinary iodine concentration and papillary thyroid cancer: A systematic review and meta-analysis
    Xueqi Zhang, Fan Zhang, Qiuxian Li, Renaguli Aihaiti, Chuyao Feng, Deshi Chen, Xu Zhao, Weiping Teng
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • Screening and validation of lymph node metastasis risk-factor genes in papillary thyroid carcinoma
    Qiaoyue Zhang, Jing Li, Hengyan Shen, Xinyu Bai, Tao Zhang, Ping Liu
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
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    Vladimir Zaichick
    Journal of Health Care and Research.2022; 3(1): 16.     CrossRef
  • Associations of Habitual Mineral Intake with New-Onset Prediabetes/Diabetes after Acute Pancreatitis
    Claire F. Norbitt, Wandia Kimita, Juyeon Ko, Sakina H. Bharmal, Maxim S. Petrov
    Nutrients.2021; 13(11): 3978.     CrossRef
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Thyroid
Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients
Heera Yang, Hyunju Park, Hyun Jin Ryu, Jung Heo, Jung-Sun Kim, Young Lyun Oh, Jun-Ho Choe, Jung Han Kim, Jee Soo Kim, Hye Won Jang, Tae Hyuk Kim, Sun Wook Kim, Jae Hoon Chung
Endocrinol Metab. 2022;37(4):652-663.   Published online July 22, 2022
DOI: https://doi.org/10.3803/EnM.2022.1477
  • 3,231 View
  • 185 Download
  • 9 Web of Science
  • 12 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Telomerase reverse transcriptase (TERT) promoter mutations are associated with increased recurrence and mortality in patients with thyroid carcinoma. Previous studies on TERT promoter mutations were retrospectively conducted on a limited number of patients.
Methods
We prospectively collected data on all consecutive patients who underwent thyroid carcinoma surgery between January 2019 and December 2020 at the Samsung Medical Center, Seoul, Korea. We included 2,092 patients with thyroid carcinoma.
Results
Of 2,092 patients, 72 patients (3.4%) had TERT promoter mutations. However, the frequency of TERT promoter mutations was 0.5% in papillary thyroid microcarcinoma (PTMC) ≤1 cm and it was 5.8% in papillary thyroid carcinoma (PTC) >1 cm. The frequency of TERT promoter mutations was significantly associated with older age at diagnosis (odds ratio [OR], 1.12; P<0.001), larger primary tumor size (OR, 2.02; P<0.001), and aggressive histological type (OR, 7.78 in follicular thyroid carcinoma; OR, 10.33 in poorly differentiated thyroid carcinoma; OR, 45.92 in anaplastic thyroid carcinoma; P<0.001). Advanced T stage, advanced N stage, and distant metastasis at diagnosis were highly prevalent in mutated thyroid cancers. However, initial distant metastasis was not present in patients with TERT promoter mutations in PTMC. Although the C228T mutation was more highly detected than the C250T mutation (64 cases vs. 7 cases), there were no significant clinicopathological differences.
Conclusion
This study is the first attempt to investigate the frequency of TERT promoter mutations in a real-world setting. The frequency of TERT promoter mutations in PTC was lower than expected, and in PTMC, young patients, and female patients, the frequency was very low.

Citations

Citations to this article as recorded by  
  • TERT Promoter Mutations Frequency Across Race, Sex, and Cancer Type
    Talal El Zarif, Marc Machaalani, Rashad Nawfal, Amin H Nassar, Wanling Xie, Toni K Choueiri, Mark Pomerantz
    The Oncologist.2024; 29(1): 8.     CrossRef
  • Gene mutations as predictors of central lymph mode metastasis in cN0 PTC: A meta‐analysis
    Jiaqi Ji, Xinlong Shi
    Clinical Genetics.2024; 105(2): 130.     CrossRef
  • Risk stratification by combining common genetic mutations and TERT promoter methylation in papillary thyroid cancer
    Ye Sang, Guanghui Hu, Junyu Xue, Mengke Chen, Shubin Hong, Rengyun Liu
    Endocrine.2024;[Epub]     CrossRef
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    Hoonsung Choi, Sun Wook Cho, Hwan Hee Kim, Ka Hee Yi, Do Joon Park, Young Joo Park
    Cancer.2024;[Epub]     CrossRef
  • Deciphering the Functions of Telomerase Reverse Transcriptase in Head and Neck Cancer
    Tsung-Jang Yeh, Chi-Wen Luo, Jeng-Shiun Du, Chien-Tzu Huang, Min-Hung Wang, Tzer-Ming Chuang, Yuh-Ching Gau, Shih-Feng Cho, Yi-Chang Liu, Hui-Hua Hsiao, Li-Tzong Chen, Mei-Ren Pan, Hui-Ching Wang, Sin-Hua Moi
    Biomedicines.2023; 11(3): 691.     CrossRef
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    Young Joo Park, Eun Kyung Lee, Young Shin Song, Soo Hwan Kang, Bon Seok Koo, Sun Wook Kim, Dong Gyu Na, Seung-Kuk Baek, So Won Oh, Min Kyoung Lee, Sang-Woo Lee, Young Ah Lee, Yong Sang Lee, Ji Ye Lee, Dong-Jun Lim, Leehi Joo, Yuh-Seog Jung, Chan Kwon Jung
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  • Thyroid Cancer, Iodine, and Gene Mutation
    Jae Hoon Chung
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    Jung Heo, Hyun Jin Ryu, Hyunju Park, Tae Hyuk Kim, Sun Wook Kim, Young Lyun Oh, Jae Hoon Chung
    Endocrine.2023;[Epub]     CrossRef
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    Michiko Matsuse, Norisato Mitsutake
    Endocrine Journal.2023; 70(11): 1035.     CrossRef
  • TERT Promoter and BRAF V600E Mutations in Papillary Thyroid Cancer: A Single-Institution Experience in Korea
    Min Jhi Kim, Jin Kyong Kim, Gi Jeong Kim, Sang-Wook Kang, Jandee Lee, Jong Ju Jeong, Woong Youn Chung, Daham Kim, Kee-Hyun Nam
    Cancers.2022; 14(19): 4928.     CrossRef
  • Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients (Endocrinol Metab 2022;37:652-63, Heera Yang et al.)
    Hyunju Park, Jae Hoon Chung
    Endocrinology and Metabolism.2022; 37(6): 949.     CrossRef
  • Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients (Endocrinol Metab 2022;37:652-63, Heera Yang et al.)
    Sue Youn Kim, Chan Kwon Jung
    Endocrinology and Metabolism.2022; 37(6): 947.     CrossRef
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Thyroid
Clinical Characteristics and Prognosis of Coexisting Thyroid Cancer in Patients with Graves’ Disease: A Retrospective Multicenter Study
Jee Hee Yoon, Meihua Jin, Mijin Kim, A Ram Hong, Hee Kyung Kim, Bo Hyun Kim, Won Bae Kim, Young Kee Shong, Min Ji Jeon, Ho-Cheol Kang
Endocrinol Metab. 2021;36(6):1268-1276.   Published online November 26, 2021
DOI: https://doi.org/10.3803/EnM.2021.1227
  • 4,481 View
  • 180 Download
  • 9 Web of Science
  • 11 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The association between Graves’ disease (GD) and co-existing thyroid cancer is still controversial and most of the previously reported data have been based on surgically treated GD patients. This study investigated the clinicopathological findings and prognosis of concomitant thyroid cancer in GD patients in the era of widespread application of ultrasonography.
Methods
Data of GD patients who underwent thyroidectomy for thyroid cancer between 2010 and 2019 in three tertiary hospitals in South Korea (Asan Medical Center, Chonnam National University Hwasun Hospital, and Pusan National University Hospital) were collected and analyzed retrospectively. In the subgroup analysis, aggressiveness and clinical outcomes of thyroid cancer were compared nodular GD and non-nodular GD groups according to the presence or absence of the thyroid nodules other than thyroid cancer (index nodules).
Results
Of the 15,159 GD patients treated at the hospitals during the study period, 262 (1.7%) underwent thyroidectomy for coexisting thyroid cancer. Eleven patients (4.2%) were diagnosed with occult thyroid cancer and 182 patients (69.5%) had microcarcinomas. No differences in thyroid cancer aggressiveness, ultrasonographic findings, or prognosis were observed between the nodular GD and non-nodular GD groups except the cancer subtype. In the multivariate analysis, only lymph node (LN) metastasis was an independent prognostic factor for recurrent/persistent disease of thyroid cancer arising in GD (P=0.020).
Conclusion
The prevalence of concomitant thyroid cancer in GD patients was considerably lower than in previous reports. The clinical outcomes of thyroid cancer in GD patients were also excellent but, more cautious follow-up is necessary for patients with LN metastasis in the same way as for thyroid cancer in non-GD patients.

Citations

Citations to this article as recorded by  
  • Comparison of Surgical Outcomes of Transoral Versus Open Thyroidectomy for Graves Disease
    Suo-Hsien Wang, Wu-Po Chao, Ta-You Lo, Soh-Ching Ng, Yu-Hsien Chen
    Surgical Laparoscopy, Endoscopy & Percutaneous Techniques.2024;[Epub]     CrossRef
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    Hanxing Sun, Hui Tong, Xiaohui Shen, Haoji Gao, Jie Kuang, Xi Chen, Qinyu Li, Weihua Qiu, Zhuoran Liu, Jiqi Yan
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    Marco Palella, Francesca Maria Giustolisi, Adriana Modica Fiascaro, Martina Fichera, Antonella Palmieri, Rossella Cannarella, Aldo E. Calogero, Margherita Ferrante, Maria Fiore
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  • Table of Contents

    Clinical Thyroidology.2022; 34(2): 48.     CrossRef
  • Predisposition to and Prognosis of Thyroid Cancer May Not Be Affected by Graves’ Disease, But Some Questions Still Remain
    Yanrui Huang, Haixia Guan
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    Andrea Marongiu, Susanna Nuvoli, Andrea De Vito, Maria Rondini, Angela Spanu, Giuseppe Madeddu
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