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Volume 34(1); March 2019
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Namgok Lecture 2018
Thyroid
Genomic Characterization of Differentiated Thyroid Carcinoma
Young Shin Song, Young Joo Park
Endocrinol Metab. 2019;34(1):1-10.   Published online March 21, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.1.1
  • 7,562 View
  • 228 Download
  • 36 Web of Science
  • 36 Crossref
AbstractAbstract PDFPubReader   ePub   

Since the release of The Cancer Genome Atlas study of papillary thyroid carcinoma (PTC) in 2014, additional genomic studies of differentiated thyroid carcinoma (DTC) using massively-parallel sequencing (MPS) have been published. Recent advances in MPS technology have started to provide important insights into the molecular pathogenesis of DTC. In the genomic landscape, the most recurrently altered genes in DTC, which has a low mutational burden relative to other cancers, are BRAF, RAS, and fusion genes. Some novel driver candidates also have been identified. The frequency of these genomic alterations varies across the subtypes of DTC (classical PTC, follicular variant of PTC, and follicular thyroid carcinoma). Telomerase reverse transcriptase (TERT) promoter mutations are the alteration that makes the most important contribution to the progression of DTC. In the transcriptomic landscape, DTC can be classified according to its gene expression profile, and each subtype has a distinct mutational profile, intracellular signaling output, and clinicopathological characteristics. Herein, we review the results of genomic studies using MPS technology, and describe the types and frequencies of genomic alterations according to histological classifications of DTC and the characteristics and significance of the gene expression signatures of DTC.

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Close layer
Review Articles
Thyroid
Mouse Models as a Tool for Understanding Progression in BrafV600E-Driven Thyroid Cancers
Iñigo Landa, Jeffrey A. Knauf
Endocrinol Metab. 2019;34(1):11-22.   Published online February 15, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.1.11
  • 6,490 View
  • 100 Download
  • 13 Web of Science
  • 12 Crossref
AbstractAbstract PDFPubReader   ePub   

The development of next generation sequencing (NGS) has led to marked advancement of our understanding of genetic events mediating the initiation and progression of thyroid cancers. The NGS studies have confirmed the previously reported high frequency of mutually-exclusive oncogenic alterations affecting BRAF and RAS proto-oncogenes in all stages of thyroid cancer. Initially identified by traditional sequencing approaches, the NGS studies also confirmed the acquisition of alterations that inactivate tumor protein p53 (TP53) and activate phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in advanced thyroid cancers. Novel alterations, such as those in telomerase reverse transcriptase (TERT) promoter and mating-type switching/sucrose non-fermenting (SWI/SNF) complex, are also likely to promote progression of the BRAFV600E-driven thyroid cancers. A number of genetically engineered mouse models (GEMM) of BRAFV600E-driven thyroid cancer have been developed to investigate thyroid tumorigenesis mediated by oncogenic BRAF and to explore the role of genetic alterations identified in the genomic analyses of advanced thyroid cancer to promote tumor progression. This review will discuss the various GEMMs that have been developed to investigate oncogenic BRAFV600E-driven thyroid cancers.

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Close layer
Miscellaneous
Search for Novel Mutational Targets in Human Endocrine Diseases
So Young Park, Myeong Han Seo, Sihoon Lee
Endocrinol Metab. 2019;34(1):23-28.   Published online March 21, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.1.23
  • 4,002 View
  • 84 Download
AbstractAbstract PDFPubReader   ePub   

The identification of disease-causing genetic variations is an important goal in the field of genetics. Advancements in genetic technology have changed scientific knowledge and made it possible to determine the basic mechanism and pathogenesis of human disorders rapidly. Many endocrine disorders are caused by genetic variations of a single gene or by mixed genetic factors. Various genetic testing methods are currently available, enabling a more precise diagnosis of many endocrine disorders and facilitating the development of a concrete therapeutic plan. In this review article, we discuss genetic testing technologies for genetic endocrine disorders, with relevant examples. We additionally describe our research on implementing genetic analysis strategies to identify novel causal mutations in hypocalcemia-related disorders.

Close layer
Thyroid
Graves' Disease: Can It Be Cured?
Wilmar M. Wiersinga
Endocrinol Metab. 2019;34(1):29-38.   Published online March 21, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.1.29
  • 17,563 View
  • 537 Download
  • 44 Web of Science
  • 49 Crossref
AbstractAbstract PDFPubReader   ePub   

Whether or not Graves' hyperthyroidism can be really cured, depends on the definition of “cure.” If eradication of thyroid hormone excess suffices for the label “cure,” then all patients can be cured because total thyroidectomy or high doses of 131I will abolish hyperthyroidism albeit at the expense of creating another disease (hypothyroidism) requiring lifelong medication with levothyroxine. I would not call this a “cure,” which I would like to define as a state with stable thyroid stimulating hormone (TSH), free thyroxine, and triiodothyronine serum concentrations in the normal range in the absence of any thyroid medication. Surgery and radioiodine are unlikely to result in so-defined cures, as their preferable aim as stated in guidelines is to cause permanent hypothyroidism. Discontinuation of antithyroid drugs is followed by 50% recurrences within 4 years; before starting therapy the risk of recurrences can be estimated with the Graves' Recurrent Events After Therapy (GREAT) score. At 20-year follow-up about 62% had developed recurrent hyperthyroidism, 8% had subclinical hypothyroidism, and 3% overt hypothyroidism related to TSH receptor blocking antibodies and thyroid peroxidase antibodies. Only 27% was in remission, and might be considered cured. If the definition of “cure” would also include the disappearance of thyroid antibodies in serum, the proportion of cured patients would become even lower.

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Close layer
Obesity and Metabolism
Implications of Mitochondrial Unfolded Protein Response and Mitokines: A Perspective on Fatty Liver Diseases
Hyon-Seung Yi
Endocrinol Metab. 2019;34(1):39-46.   Published online March 21, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.1.39
  • 6,306 View
  • 146 Download
  • 27 Web of Science
  • 26 Crossref
AbstractAbstract PDFPubReader   ePub   

The signaling network of the mitochondrial unfolded protein response (UPRmt) and mitohormesis is a retrograde signaling pathway through which mitochondria-to-nucleus communication occurs in organisms. Recently, it has been shown that the UPRmt is closely associated with metabolic disorders and conditions involving insulin resistance, such as alcoholic and non-alcoholic fatty liver and fibrotic liver disease. Scientific efforts to understand the UPRmt and mitohormesis, as well as to establish the mitochondrial proteome, have established the importance of mitochondrial quality control in the development and progression of metabolic liver diseases, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In this review, we integrate and discuss the recent data from the literature on the UPRmt and mitohormesis in metabolic liver diseases, including NAFLD/NASH and fibrosis.

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Close layer
Obesity and Metabolism
Myths about Insulin Resistance: Tribute to Gerald Reaven
Sun H. Kim, Fahim Abbasi
Endocrinol Metab. 2019;34(1):47-52.   Published online March 21, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.1.47
  • 7,154 View
  • 149 Download
  • 3 Web of Science
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AbstractAbstract PDFPubReader   ePub   

Gerald Reaven was often called the “father of insulin resistance.” On the 1-year anniversary of his death in 2018, we challenge three myths associated with insulin resistance: metformin improves insulin resistance; measurement of waist circumference predicts insulin resistance better than body mass index; and insulin resistance causes weight gain. In this review, we highlight Reaven's relevant research that helped to dispel these myths associated with insulin resistance.

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Close layer
Special Article
Hypothalamus and Pituitary gland
Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement
Sang Ouk Chin, Cheol Ryong Ku, Byung Joon Kim, Sung-Woon Kim, Kyeong Hye Park, Kee Ho Song, Seungjoon Oh, Hyun Koo Yoon, Eun Jig Lee, Jung Min Lee, Jung Soo Lim, Jung Hee Kim, Kwang Joon Kim, Heung Yong Jin, Dae Jung Kim, Kyung Ae Lee, Seong-Su Moon, Dong Jun Lim, Dong Yeob Shin, Se Hwa Kim, Min Jeong Kwon, Ha Young Kim, Jin Hwa Kim, Dong Sun Kim, Chong Hwa Kim
Endocrinol Metab. 2019;34(1):53-62.   Published online March 21, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.1.53
  • 6,936 View
  • 270 Download
  • 8 Web of Science
  • 11 Crossref
AbstractAbstract PDFPubReader   ePub   

The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach.

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Close layer
Original Articles
Thyroid
99mTc-Pertechnetate Scintigraphy Predicts Successful Postoperative Ablation in Differentiated Thyroid Carcinoma Patients Treated with Low Radioiodine Activities
Luca Giovanella, Gaetano Paone, Teresa Ruberto, Luca Ceriani, Pierpaolo Trimboli
Endocrinol Metab. 2019;34(1):63-69.   Published online February 15, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.1.63
  • 4,625 View
  • 73 Download
  • 6 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Background

Postoperative routine radioiodine (RAI) treatment is currently debated for patients with low-risk differentiated thyroid carcinoma (DTC) patients. If performed, a low 131I activity (i.e., 1 to 2 GBq) is recommended with the aim to ablate thyroid remnant and facilitate subsequent follow-up by thyroglobulin measurement. The purpose of this study was to evaluate the relationship between postsurgical technetium-99m (99mTc)-pertechnetate scintigraphy and the rate of successful remnant ablation after low activity radioiodine ablation in patients with DTC.

Methods

Enrolled were 193 patients with low risk DTC who underwent total thyroidectomy and RAI ablation with a fixed 1.1 GBq activity of 131I. 99mTc-pertechnetate scans were done and thyrotropin stimulated thyroglobulin (sTg) levels measured just before ablation. Ablation effectiveness was assessed 6 to 12 months later by sTg measurement, neck ultrasound and diagnostic whole body scan.

Results

A negative 99mTc-perthecnetate scans was the best predictor of successful ablation (P<0.001) followed by preablative sTg levels <0.8 ng/mL (P=0.008) and 99mTc-pertechnetate uptake rate values <0.9% (P=0.065). Neither sex nor age of the patient at the time of ablation or tumor histology and size showed a significant association with the rate of successful ablation.

Conclusion

The 99mTc-pertechnetate scintigraphy is a simple and feasible tool to predict effectiveness of low activity 131I thyroid to ablate thyroid remnants in patients with DTC.

Citations

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  • Combined clinical variable and radiomics of post-treatment total body scan for prediction of successful I-131 ablation in low-risk papillary thyroid carcinoma patients
    Maythinee Chantadisai, Jirarot Wongwijitsook, Napat Ritlumlert, Yothin Rakvongthai
    Scientific Reports.2024;[Epub]     CrossRef
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    Antonio Matrone, Alessio Faranda, Francesco Latrofa, Carla Gambale, Delio Stefani Donati, Eleonora Molinaro, Laura Agate, David Viola, Paolo Piaggi, Liborio Torregrossa, Fulvio Basolo, Rossella Elisei
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Close layer
Diabetes
Retrospective Analysis of the Efficacy of Dapagliflozin in Patients with Type 2 Diabetes in a Primary Clinic in Korea
Sang Hyun Park, Young Ju Choi, Eun-Jung Rhee, Kab Bum Huh
Endocrinol Metab. 2019;34(1):70-79.   Published online March 21, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.1.70
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  • 100 Download
  • 1 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Background

We aimed to retrospectively analyze the efficacy of 10 mg dapagliflozin (DAPA), which is a sodium-glucose cotransporter-2 inhibitor, in Korean patients with type 2 diabetes who visited a primary diabetes clinic.

Methods

In total, 83 patients with type 2 diabetes, who received treatment with DAPA for the first time in a primary diabetes clinic between January 2015 and October 2015, were included in the study. The effect of DAPA in lowering glycosylated hemoglobin (HbA1c) levels was evaluated via chart review at 6 months follow-up. The patients were categorized into five groups according to add-on to or switched from other glucose-lowering agents: add-on to metformin (MET, n=10), add-on to MET+dipeptidyl peptidase 4 inhibitor (DPP4i, n=12), switched from sulfonylurea (SU, n=13), switched from DPP4i (n=11), and switched from thiazolidinedione (TZD, n=37). All the participants had already used MET for their regimen.

Results

Treatment with DAPA reduced HbA1c level by 1.2%±0.8%. Moreover, a significant decrease was observed in all subgroups: add-on to MET, −1.2%±0.7%; add-on to MET+DPP4i, −1.4%±0.8%; switched from SU, −1.4%±0.7%; switched from DPP4i, −0.5%±0.7%; and switched from TZD, −1.2%±0.9% (P<0.01). A significant decrease in body weight (−3.1±2.6 kg, P<0.001) was observed after DAPA administration. Estimated glomerular filtration rate and urine microalbumin were significantly decreased after 6 months of treatment with DAPA (−4.0±13.5 mL/min/1.73 m2, P=0.03; −23.6±45.9 mg/L, P<0.001).

Conclusion

Treatment with DAPA, whether added to or switched from other glucose-lowering agents, significantly decreased HbA1c levels in Korean patients with type 2 diabetes who visited a single primary diabetes clinic. DAPA can be considered as an optimal second-line treatment for patients with type 2 diabetes, as supported by real-world evidence studies.

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    Vandana Veenit, Hiddo J L Heerspink, Christine Ahlström, Peter J Greasley, Stanko Skritic, Natalie van Zuydam, Donald E Kohan, Pernille B L Hansen, Robert I Menzies
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Diabetes
Effects of Dipeptidyl Peptidase-4 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
Jae Hyun Bae, Sunhee Kim, Eun-Gee Park, Sin Gon Kim, Seokyung Hahn, Nam Hoon Kim
Endocrinol Metab. 2019;34(1):80-92.   Published online March 21, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.1.80
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

To investigate the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on renal outcomes in patients with type 2 diabetes.

Methods

MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched to identify randomized controlled trials (RCTs) of DPP-4 inhibitors from inception to September 2017. We selected eligible RCTs comparing DPP-4 inhibitors with placebo or other antidiabetic agents and reporting at least one renal outcome. A meta-analysis was conducted to calculate standardized mean differences, weighted mean differences (WMDs), relative risks (RRs), and 95% confidence intervals (CIs) for each renal outcome.

Results

We included 23 RCTs with 19 publications involving 41,359 patients. Overall changes in urine albumin-to-creatinine ratio were comparable between DPP-4 inhibitors and controls (P=0.150). However, DPP-4 inhibitors were associated with significantly lower risk of incident microalbuminuria (RR, 0.89; 95% CI, 0.80 to 0.98; P=0.022) and macroalbuminuria (RR, 0.77; 95% CI, 0.61 to 0.97; P=0.027), as well as higher rates of regression of albuminuria (RR, 1.22; 95% CI, 1.10 to 1.35; P<0.001) compared with controls. Although DPP-4 inhibitors were associated with small but significantly lower estimated glomerular filtration rate (WMD, −1.11 mL/min/1.73 m2; 95% CI, −1.78 to −0.44; P=0.001), there was no difference in the risk of end-stage renal disease between two groups (RR, 0.93; 95% CI, 0.76 to 1.14; P=0.475).

Conclusion

DPP-4 inhibitors had beneficial renal effects mainly by reducing the risk of development or progression of albuminuria compared with placebo or other antidiabetic agents.

Citations

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Endocrinol Metab : Endocrinology and Metabolism