Background The predictive factors for lateral neck lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) remain undetermined. This study investigated the clinicopathological characteristics, transcriptomes, and tumor microenvironment in PTMC according to the LLNM status. We aimed to identify the biomarkers associated with LLNM development.
Methods We retrospectively reviewed the medical records of patients with PTMC from two independent institutions between 2018 and 2022 (n=597 and n=467). We compared clinicopathological features between patients without lymph node metastasis (N0) and those with LLNM (N1b). Additionally, laser capture microdissection and RNA sequencing were performed on primary tumors from both groups, including metastatic lymph nodes from the N1b group (n=30; 20 primary tumors and 10 paired LLNMs). We corroborated the findings using RNA sequencing data from 16 BRAF-like PTMCs from The Cancer Genome Atlas. Transcriptomic analyses were validated by immunohistochemical staining.
Results Clinicopathological characteristics, such as male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis showed associations with LLNM in PTMCs. Transcriptomic profiles between the N0 and N1b PTMC groups were similar. However, tumor microenvironment deconvolution from RNA sequencing and immunohistochemistry revealed an increased abundance of tumor-associated macrophages, particularly M2 macrophages, in the N1b group.
Conclusion Patients with PTMC who have a male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis exhibited an elevated risk for LLNM. Furthermore, infiltration of M2 macrophages in the tumor microenvironment potentially supports tumor progression and LLNM in PTMCs.
Background This study evaluated the effects of a mobile diabetes management program called “iCareD” (College of Medicine, The Catholic University of Korea) which was integrated into the hospital’s electronic medical records system to minimize the workload of the healthcare team in the real clinical practice setting.
Methods In this retrospective observational study, we recruited 308 patients. We categorized these patients based on their compliance regarding their use of the iCareD program at home; compliance was determined through self-monitored blood glucose inputs and message subscription rates. We analyzed changes in the ABC (hemoglobin A1c, blood pressure, and low-density lipoprotein cholesterol) levels from the baseline to 12 months thereafter, based on the patients’ iCareD usage patterns.
Results The patients comprised 92 (30%) non-users, 170 (55%) poor-compliance users, and 46 (15%) good-compliance users; the ABC target achievement rate showed prominent changes in good-compliance groups from baseline to 12 months (10.9% vs. 23.9%, P<0.05), whereas no significant changes were observed for poor-compliance users and non-users (13.5% vs. 18.8%, P=0.106; 20.7% vs. 14.1%, P=0.201; respectively).
Conclusion Implementing the iCareD can improve the ABC levels of patients with diabetes with minimal efforts of the healthcare team in real clinical settings. However, the improvement of patients’ compliance concerning the use of the system without the vigorous intervention of the healthcare team needs to be solved in the future.
The 2023 Korean Thyroid Association (KTA) Management Guideline for Patients with Thyroid Nodules constitute an update of the 2016 KTA guideline for thyroid nodules and cancers that focuses specifically on nodules. The 2023 guideline aim to offer updated guidance based on new evidence that reflects the changes in clinical practice since the 2016 KTA guideline. To update the 2023 guideline, a comprehensive literature search was conducted from January 2022 to May 2022. The literature search included studies, reviews, and other evidence involving human subjects that were published in English in MEDLINE (PubMed), Embase, and other relevant databases. Additional significant clinical trials and research studies published up to April 2023 were also reviewed. The limitations of the current evidence are discussed, and suggestions for areas in need of further research are identified. The purpose of this review is to provide a summary of the 2023 KTA guideline for the management of thyroid nodules released in May 2023 and to give a balanced insight with comparison of recent guidelines from other societies.
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Pituitary neuroendocrine tumors (PitNETs) are the third most frequently diagnosed intracranial tumors, with nonfunctioning PitNETs (nfPitNETs) accounting for 30% of all pituitary tumors and representing the most common type of macroPitNETs. NfPitNETs are usually benign tumors with no evidence of hormone oversecretion except for hyperprolactinemia secondary to pituitary stalk compression. Due to this, they do not typically present with clinical syndromes like acromegaly, Cushing’s disease or hyperthyroidism and instead are identified incidentally on imaging or from symptoms of mass effects (headache, vision changes, apoplexy). With the lack of effective medical interventions, first-line treatment is transsphenoidal surgical resection, however, nfPitNETs often have supra- or parasellar extension, and total resection of the tumor is often not possible, resulting in residual tumor regrowth or reoccurrence. While functional PitNETs can be easily followed for recurrence using hormonal biomarkers, there is no similar parameter to predict recurrence in nfPitNETs, hence delaying early recognition and timely management. Therefore, there is a need to identify prognostic biomarkers that can be used for patient surveillance and as therapeutic targets. This review focuses on summarizing the current evidence on nfPitNETs, with a special focus on potential new biomarkers and therapeutics.
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Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung, The Committee of Clinical Practice Guideline of Korean Endocrine Society, The Korean Adrenal Study Group of Korean Endocrine Society
Endocrinol Metab. 2023;38(6):597-618. Published online October 13, 2023
Primary aldosteronism (PA) is a common, yet underdiagnosed cause of secondary hypertension. It is characterized by an overproduction of aldosterone, leading to hypertension and/or hypokalemia. Despite affecting between 5.9% and 34% of patients with hypertension, PA is frequently missed due to a lack of clinical awareness and systematic screening, which can result in significant cardiovascular complications. To address this, medical societies have developed clinical practice guidelines to improve the management of hypertension and PA. The Korean Endocrine Society, drawing on a wealth of research, has formulated new guidelines for PA. A task force has been established to prepare PA guidelines, which encompass epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and follow-up care. The Korean clinical guidelines for PA aim to deliver an evidence-based protocol for PA diagnosis, treatment, and patient monitoring. These guidelines are anticipated to ease the burden of this potentially curable condition.
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Subclinical hypothyroidism (SCH) is characterized by elevated thyroid-stimulating hormone (TSH) and normal free thyroxine levels. The Korean Thyroid Association recently issued a guideline for managing SCH, which emphasizes Korean-specific TSH diagnostic criteria and highlights the health benefits of levothyroxine (LT4) treatment. A serum TSH level of 6.8 mIU/L is presented as the reference value for diagnosing SCH. SCH can be classified as mild (TSH 6.8 to 10.0 mIU/L) or severe (TSH >10.0 mIU/L), and patients can be categorized as adults (age <70 years) or elderly (age ≥70 years), depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, including a thyroid peroxidase antibody test, preferably 2 to 3 months after the initial assessment. While LT4 treatment is not generally recommended for mild SCH in adults, it is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and it may be considered for those with concurrent dyslipidemia. Conversely, LT4 treatment is generally not recommended for elderly patients, regardless of SCH severity. For those SCH patients who are prescribed LT4 treatment, the dosage should be personalized, and serum TSH levels should be regularly monitored to maintain the optimal LT4 regimen.
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Background Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs.
Methods We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment.
Results Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection- invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status.
Conclusion The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs.
Autism spectrum disorder (ASD), with its high economic and societal costs, is a growing public health concern whose prevalence has risen steadily over the last two decades. Although actual increased incidence versus improved diagnosis remains controversial, the increased prevalence of ASD suggests non-inherited factors as likely contributors. There is increasing epidemiologic evidence that abnormal maternal thyroid function during pregnancy is associated with increased risk of child ASD and other neurodevelopmental disorders. Prenatal exposure to endocrine-disrupting chemicals such as per- and polyfluoroalkyl substances (PFAS) is known to disrupt thyroid function and can affect early brain development; thus, thyroid dysfunction is hypothesized to mediate this relationship. The concept of a potential pathway from prenatal PFAS exposure through thyroid dysfunction to ASD etiology is not new; however, the extant literature on this topic is scant. The aim of this review is to evaluate and summarize reports with regard to potential mechanisms in this pathway.
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Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the standard method for surgery, minimally invasive parathyroidectomy (MIP), or focused parathyroidectomy, has been widely accepted with comparable curative outcomes. For successful MIP, accurate preoperative localization of parathyroid lesions is essential. However, no consensus exists on the optimal approach for localization. Currently, ultrasonography and technetium-99m-sestamibi–single photon emission computed tomography/computed tomography are widely accepted in most cases. However, exact localization cannot always be achieved, especially in cases with multiglandular disease, ectopic glands, recurrent disease, and normocalcemic primary hyperparathyroidism. Therefore, new modalities for preoperative localization have been developed and evaluated. Positron emission tomography/computed tomography and parathyroid venous sampling have demonstrated improvements in sensitivity and accuracy. Both anatomical and functional information can be obtained by combining these methods. As each approach has its advantages and disadvantages, the localization study should be deliberately chosen based on each patient’s clinical profile, costs, radiation exposure, and the availability of experienced experts. In this review, we summarize various methods for the localization of hyperfunctioning parathyroid tissues in primary hyperparathyroidism.
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Original Articles
Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Background The present study investigates whether modifiable behavioral factors of current cigarette smoking, heavy alcohol consumption, and regular exercise are associated with risk of lower extremity amputation (LEA) in diabetic patients.
Methods A total of 2,644,440 diabetic patients (aged ≥20 years) was analyzed using the database of the Korean National Health Insurance Service. Cox proportional hazard regression was used to assess adjusted hazard ratios (HRs) for the behavioral factors with risk of LEA under adjustment for potential confounders.
Results The risk of LEA was significantly increased by current cigarette smoking and heavy alcohol consumption (HR, 1.436; 95% confidence interval [CI], 1.367 to 1.508 and HR, 1.082; 95% CI, 1.011 to 1.158) but significantly decreased with regular exercise (HR, 0.745; 95% CI, 0.706 to 0.786) after adjusting for age, sex, smoking, alcohol consumption, exercise, low income, hypertension, dyslipidemia, body mass index, using insulin or oral antidiabetic drugs, and diabetic duration. A synergistically increased risk of LEA was observed with larger number of risky behaviors.
Conclusion Modification of behaviors of current smoking, heavy alcohol intake, and exercise prevents LEA and can improve physical, emotional, and social quality of life in diabetic patients.
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Background Since image-based fracture prediction models using deep learning are lacking, we aimed to develop an X-ray-based fracture prediction model using deep learning with longitudinal data.
Methods This study included 1,595 participants aged 50 to 75 years with at least two lumbosacral radiographs without baseline fractures from 2010 to 2015 at Seoul National University Hospital. Positive and negative cases were defined according to whether vertebral fractures developed during follow-up. The cases were divided into training (n=1,416) and test (n=179) sets. A convolutional neural network (CNN)-based prediction algorithm, DeepSurv, was trained with images and baseline clinical information (age, sex, body mass index, glucocorticoid use, and secondary osteoporosis). The concordance index (C-index) was used to compare performance between DeepSurv and the Fracture Risk Assessment Tool (FRAX) and Cox proportional hazard (CoxPH) models.
Results Of the total participants, 1,188 (74.4%) were women, and the mean age was 60.5 years. During a mean follow-up period of 40.7 months, vertebral fractures occurred in 7.5% (120/1,595) of participants. In the test set, when DeepSurv learned with images and clinical features, it showed higher performance than FRAX and CoxPH in terms of C-index values (DeepSurv, 0.612; 95% confidence interval [CI], 0.571 to 0.653; FRAX, 0.547; CoxPH, 0.594; 95% CI, 0.552 to 0.555). Notably, the DeepSurv method without clinical features had a higher C-index (0.614; 95% CI, 0.572 to 0.656) than that of FRAX in women.
Conclusion DeepSurv, a CNN-based prediction algorithm using baseline image and clinical information, outperformed the FRAX and CoxPH models in predicting osteoporotic fracture from spine radiographs in a longitudinal cohort.
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Sestrin2, a well-known adenosine monophosphate-activated protein kinase (AMPK) regulator, plays a protective role against metabolic stress. The β3-adrenergic receptor (β3AR) induces fat browning and inhibits muscle atrophy in an AMPK-dependent manner. However, no prior research has examined the relationship of sestrin2 with β3AR in body composition changes. In this study, CL 316,243 (CL), a β3AR agonist, was administered to wild-type and sestrin2-knockout (KO) mice for 2 weeks, and fat and muscle tissues were harvested. CL induced AMPK phosphorylation, expression of brown-fat markers, and mitochondrial biogenesis, which resulted in the reduction of lipid droplet size in inguinal white adipose tissue (iWAT). These effects were not observed in sestrin2-KO mice. In CL-treated soleus muscle, sestrin2-KO was related to decreased myogenic gene expression and increased levels of muscle atrophy-related molecules. Our results suggest that sestrin2 is associated with beneficial β3AR-mediated changes in body composition, especially in iWAT and in the soleus.
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Sestrin2 levels in patients with anxiety and depression myocardial infarction was up-regulated and suppressed inflammation and ferroptosis by LKB1-mediated AMPK activation Yufeng Qian, Lian Chen, Beibei Gao, Xianhua Ye Clinical and Experimental Hypertension.2023;[Epub] CrossRef
Sestrin2 in diabetes and diabetic complications Xiaodan Zhang, Zirui Luo, Jiahong Li, Yaxuan Lin, Yu Li, Wangen Li Frontiers in Endocrinology.2023;[Epub] CrossRef