Endocrinology and Metabolism

Volume 37(2); April 2022

Review Articles

Calcium & Bone Metabolism
Discontinuing Denosumab: Can It Be Done Safely? A Review of the Literature: Wei Lin Tay, Donovan Tay; Endocrinol Metab. 2022;37(2):183-194. Published online April 14, 2022; DOI: https://doi.org/10.3803/EnM.2021.1369

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Denosumab, which has been approved for the treatment of osteoporosis since 2010, is a fully humanised monoclonal antibody against a cytokine, receptor activator of nuclear factor kappa B ligand (RANKL), involved in bone resorption. Continued use of denosumab results in a potent and sustained decrease in bone turnover, an increase in bone mineral density (BMD), and a reduction in vertebral and hip fractures. The anti-resorptive effects of denosumab are reversible upon cessation, and this reversal is accompanied by a transient marked increase in bone turnover that is associated with bone loss, and of concern, an increased risk of multiple vertebral fractures. In this review, we outline the effects of denosumab withdrawal on bone turnover markers, BMD, histomorphometry, and fracture risk. We provide an update on recent clinical trials that sought to answer how clinicians can transition away from denosumab safely with follow-on therapy to mitigate bone loss and summarise the recommendations of various international guidelines.

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Multiple vertebral fractures after antiosteoporotic medications discontinuation: A comparative study to evaluate the potential rebound effect of denosumab
Mar Martín-Pérez, Beatriz Sánchez-Delgado, Patricia García-Poza, Sergio López-Álvarez, Elisa Martín-Merino
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Denosumab: A Useful Addition to the Armamentarium for the Management of Male Osteoporosis
Jijith Krishnan, Sham Santhanam, Bhuwan Singh, Salim Patel, Divya G Bhojwani, Sameer Muchhala
Cureus.2024;[Epub] CrossRef
Enhancing Treatment Success in Osteoporosis: Optimising the Use of Teriparatide

European Medical Journal.2024; : 49. CrossRef
Denosumab combined with chemotherapy followed by anlotinib in the treatment of multiple metastases of malignant peripheral nerve sheath tumor: a case report and literature review
Qian Chen, Haocheng Cui, Kai Zheng, Ming Xu, Xiuchun Yu
Frontiers in Oncology.2024;[Epub] CrossRef
The use of denosumab in osteoporosis – an update on efficacy and drug safety
Dima L. Diab, Nelson B. Watts
Expert Opinion on Drug Safety.2024; 23(9): 1069. CrossRef
Denosumab in Osteoporosis: Predicting Long-Term Efficacy beyond 10 Years
Jeongmin Lee, Youn-Ju Lee, Jeonghoon Ha
Journal of Bone Metabolism.2024; 31(3): 246. CrossRef
Osteoporose – Definition, Risikoerfassung, Diagnose, Prävention und Therapie (Update 2024)
Hans Peter Dimai, Christian Muschitz, Karin Amrein, Rosemarie Bauer, Daniel Cejka, Rudolf Wolfgang Gasser, Reinhard Gruber, Judith Haschka, Timothy Hasenöhrl, Franz Kainberger, Katharina Kerschan-Schindl, Roland Kocijan, Jürgen König, Norbert Kroißenbrunn
Wiener klinische Wochenschrift.2024; 136(S16): 599. CrossRef
Denosumab stimulates spermatogenesis in infertile men with preserved Sertoli cell capacity
Christine H. Andreassen, Rune Holt, Li Juel Mortensen, Nadia Krarup Knudsen, John E. Nielsen, Nadia Nicholine Poulsen, Sam K. Yahyavi, Ida M. Boisen, Zhihui Cui, Luisina Ongaro, Jasmin P. Hjerresen, Birgitte G. Toft, Thomas Hasselager, Niklas R. Jørgensen
Cell Reports Medicine.2024; 5(10): 101783. CrossRef
Loss of lower extremity bone mineral density 1 year after denosumab is discontinued in persons with subacute spinal cord injury
Christopher M. Cirnigliaro, Michael F. La Fountaine, J. Scott Parrott, Steven C. Kirshblum, Susan J. Sauer, Sue A. Shapses, Isa A. McClure, William A. Bauman
Osteoporosis International.2023; 34(4): 741. CrossRef
Persistence with Denosumab in Male Osteoporosis Patients: A Real-World, Non-Interventional Multicenter Study
Chaiho Jeong, Jeongmin Lee, Jinyoung Kim, Jeonghoon Ha, Kwanhoon Jo, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Tae-Seo Sohn, Ki-Ho Song, Moo Il Kang, Ki-Hyun Baek
Endocrinology and Metabolism.2023; 38(2): 260. CrossRef

Diabetes, Obesity and Metabolism
A Study on Methodologies of Drug Repositioning Using Biomedical Big Data: A Focus on Diabetes Mellitus: Suehyun Lee, Seongwoo Jeon, Hun-Sung Kim; Endocrinol Metab. 2022;37(2):195-207. Published online April 13, 2022; DOI: https://doi.org/10.3803/EnM.2022.1404

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Drug repositioning is a strategy for identifying new applications of an existing drug that has been previously proven to be safe. Based on several examples of drug repositioning, we aimed to determine the methodologies and relevant steps associated with drug repositioning that should be pursued in the future. Reports on drug repositioning, retrieved from PubMed from January 2011 to December 2020, were classified based on an analysis of the methodology and reviewed by experts. Among various drug repositioning methods, the network-based approach was the most common (38.0%, 186/490 cases), followed by machine learning/deep learningbased (34.3%, 168/490 cases), text mining-based (7.1%, 35/490 cases), semantic-based (5.3%, 26/490 cases), and others (15.3%, 75/490 cases). Although drug repositioning offers several advantages, its implementation is curtailed by the need for prior, conclusive clinical proof. This approach requires the construction of various databases, and a deep understanding of the process underlying repositioning is quintessential. An in-depth understanding of drug repositioning could reduce the time, cost, and risks inherent to early drug development, providing reliable scientific evidence. Furthermore, regarding patient safety, drug repurposing might allow the discovery of new relationships between drugs and diseases.

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The Present and Future of Artificial Intelligence-Based Medical Image in Diabetes Mellitus: Focus on Analytical Methods and Limitations of Clinical Use
Ji-Won Chun, Hun-Sung Kim
Journal of Korean Medical Science.2023;[Epub] CrossRef

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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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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The ageing thyroid: implications for longevity and patient care
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Incidence and Determinants of Spontaneous Normalization of Subclinical Hypothyroidism in Older Adults
Evie van der Spoel, Nicolien A van Vliet, Rosalinde K E Poortvliet, Robert S Du Puy, Wendy P J den Elzen, Terence J Quinn, David J Stott, Naveed Sattar, Patricia M Kearney, Manuel R Blum, Heba Alwan, Nicolas Rodondi, Tinh-Hai Collet, Rudi G J Westendorp,
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Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications
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Evaluation of multiple organophosphate insecticide exposure in relation to altered thyroid hormones in NHANES 2007‐2008 adult population
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Thyroid-function reference ranges in the diagnosis of thyroid dysfunction in adults
Salman Razvi
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Association between exposure to chemical mixtures and epigenetic ageing biomarkers: Modifying effects of thyroid hormones and physical activity
Wanying Shi, Jianlong Fang, Huimin Ren, Peijie Sun, Juan Liu, Fuchang Deng, Shuyi Zhang, Qiong Wang, Jiaonan Wang, Shilu Tong, Song Tang, Xiaoming Shi
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Biochemical pattern and prevalence of thyroid disorders among adults in a tertiary hospital in North-East Nigeria
Bawa Ibrahim Abubkar, Longwap Abdulazis Saleh, Dauda E. Suleiman, Sanni Musa, Bosede Oluwasayo Adegoke, Ibrahim Naziru, Abbas Hamisu, Harisu Salisu, Rabi’atu Ahmad Bichi, Mansur Ramalan Aliyu, Christian Isichei
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Analysis of Inflammatory and Thyroid Hormone Levels Based on Hepatitis A and B Virus Immunity Status: Age and Sex Stratification
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Hypothyroidism
Peter N Taylor, Marco M Medici, Alicja Hubalewska-Dydejczyk, Kristien Boelaert
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Thyroid dysfunction among patients assessed by thyroid function tests at a tertiary care hospital: a retrospective study
Emmanuel Donkoh Aidoo, Grace Korkor Ababio, Benjamin Arko-Boham, Emmanuel Ayitey Tagoe, Nii Ayite Aryee
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DNA Methylation in Autoimmune Thyroid Disease
Nicole Lafontaine, Scott G Wilson, John P Walsh
The Journal of Clinical Endocrinology & Metabolism.2023; 108(3): 604. CrossRef
A Causality between Thyroid Function and Bone Mineral Density in Childhood: Abnormal Thyrotropin May Be Another Pediatric Predictor of Bone Fragility
Dongjin Lee, Moon Ahn
Metabolites.2023; 13(3): 372. CrossRef
Serum Lipidomic Analysis Reveals Biomarkers and Metabolic Pathways of Thyroid Dysfunction
Hua Dong, Wenjie Zhou, Xingxu Yan, Huan Zhao, Honggang Zhao, Yan Jiao, Guijiang Sun, Yubo Li, Zuncheng Zhang
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Developmental and environmental modulation of fecal thyroid hormone levels in wild Assamese macaques (Macaca assamensis)
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Prevalence of Functional Alterations and the Effects of Thyroid Autoimmunity on the Levels of TSH in an Urban Population of Colombia: A Population-Based Study
Hernando Vargas-Uricoechea, Valentina Agredo-Delgado, Hernando David Vargas-Sierra, María V. Pinzón-Fernández
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Genetic determinants of thyroid function in children
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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Relationship between Thyroid CT Density, Volume, and Future TSH Elevation: A 5-Year Follow-Up Study
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Thyroid Stimulating Hormone and Thyroid Hormones (Triiodothyronine and Thyroxine): An American Thyroid Association-Commissioned Review of Current Clinical and Laboratory Status
Katleen Van Uytfanghe, Joel Ehrenkranz, David Halsall, Kelly Hoff, Tze Ping Loh, Carole A. Spencer, Josef Köhrle
Thyroid®.2023; 33(9): 1013. CrossRef
Blood hormones and suicidal behaviour: A systematic review and meta-analysis
Xue-Lei Fu, Xia Li, Jia-Mei Ji, Hua Wu, Hong-Lin Chen
Neuroscience & Biobehavioral Reviews.2022; 139: 104725. CrossRef

Editorial

Thyroid
Effect of Hyperthyroidism on Preventing Renal Insufficiency: Tae Yong Kim; Endocrinol Metab. 2022;37(2):220. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2022.201

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Therapeutic effect of Corbrin (Bailing) capsule on patients with renal insufficiency: A meta-analysis
Xiaoling Zhou, Jianhua Ye, Xiaoyan Guo, Menghua Chen
Heliyon.2024; 10(8): e29488. CrossRef

Original Articles

Diabetes, Obesity and Metabolism
Stimulation of Alpha-1-Adrenergic Receptor Ameliorates Obesity-Induced Cataracts by Activating Glycolysis and Inhibiting Cataract-Inducing Factors: Yong-Jik Lee, Yoo-Na Jang, Hyun-Min Kim, Yoon-Mi Han, Hong Seog Seo, Youngsub Eom, Jong-suk Song, Ji Hoon Jeong, Tae Woo Jung; Endocrinol Metab. 2022;37(2):221-232. Published online March 23, 2022; DOI: https://doi.org/10.3803/EnM.2021.1237

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Background
Obesity, the prevalence of which is increasing due to the lack of exercise and increased consumption of Westernized diets, induces various complications, including ophthalmic diseases. For example, obesity is involved in the onset of cataracts.
Methods
To clarify the effects and mechanisms of midodrine, an α1-adrenergic receptor agonist, in cataracts induced by obesity, we conducted various analytic experiments in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a rat model of obesity.
Results
Midodrine prevented cataract occurrence and improved lens clearance in OLETF rats. In the lenses of OLETF rats treated with midodrine, we observed lower levels of aldose reductase, tumor necrosis factor-α, and sorbitol, but higher levels of hexokinase, 5’-adenosine monophosphate-activated protein kinase-alpha, adenosine 5´-triphosphate, peroxisome proliferator-activated receptordelta, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, superoxide dismutase, and catalase.
Conclusion
The ameliorating effects of midodrine on cataracts in the OLETF obesity rat model are exerted via the following three mechanisms: direct inhibition of the biosynthesis of sorbitol, which causes cataracts; reduction of reactive oxygen species and inflammation; and (3) stimulation of normal aerobic glycolysis.

Citations

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A review on drug repurposing applicable to obesity
Feng Chen, Kai Jing, Zhen Zhang, Xia Liu
Obesity Reviews.2024;[Epub] CrossRef
α1-Adrenergic Receptors: Insights into Potential Therapeutic Opportunities for COVID-19, Heart Failure, and Alzheimer’s Disease
Dianne M. Perez
International Journal of Molecular Sciences.2023; 24(4): 4188. CrossRef
A new use for old drugs: identifying compounds with an anti-obesity effect using a high through-put semi-automated Caenorhabditis elegans screening platform
Freek Haerkens, Charlotte Kikken, Laurens Kirkels, Monique van Amstel, Willemijn Wouters, Els van Doornmalen, Christof Francke, Samantha Hughes
Heliyon.2022; 8(8): e10108. CrossRef

Diabetes, Obesity and Metabolism
Comparative Study of Ex Vivo Antiplatelet Activity of Aspirin and Cilostazol in Patients with Diabetes and High Risk of Cardiovascular Disease: Sangmo Hong, Woo Je Lee, Cheol-Young Park; Endocrinol Metab. 2022;37(2):233-242. Published online April 6, 2022; DOI: https://doi.org/10.3803/EnM.2021.1353

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Abstract PDF Supplementary Material PubReader ePub: Background
The role of aspirin in primary cardiovascular disease prevention in patients with diabetes remains controversial. However, some studies have suggested beneficial effects of cilostazol on cardiovascular disease in patients with diabetes. We prospectively investigated the antiplatelet effects of cilostazol compared with aspirin in patients with diabetes and cardiovascular risk factors.
Methods
We randomly assigned 116 patients with type 2 diabetes and cardiovascular risk factors but no evident cardiovascular disease to receive aspirin at a dose of 100 mg or cilostazol at a dose of 200 mg daily for 14 days. The primary efficacy outcome was antiplatelet effects of aspirin and cilostazol assessed with the VerifyNow system (aspirin response units [ARU]) and PFA-100 (closure time [CT]). Secondary outcomes were changes of clinical laboratory data (ClinicalTrials.gov Identifier: NCT02933788).
Results
After 14 days, there was greater decrease in ARU in aspirin (–28.9%±9.9%) compared cilostazol (–0.4%±7.1%, P<0.001) and was greater increase in CT in aspirin (99.6%±63.5%) compared cilostazol (25.7%±54.1%, P<0.001). The prevalence of aspirin resistance was 7.5% according to VerifyNow (defined by ARU ≥550) and 18.9% according to PFA-100 (CT <192 seconds). Compared with aspirin, cilostazol treatment was associated with increased high density lipoprotein cholesterol (7.1%±12.7% vs. 4.2%±18.0%, P=0.006) and decreased triglycerides (–9.4%±33.7% vs. 4.4%±17.57%, P=0.016). However, there were no significant changes in total and low density lipoprotein cholesterol, C-reactive protein level, and cluster of differentiation 40 ligand between cilostazol and aspirin groups.
Conclusion
Aspirin showed better antiplatelet effects assessed with VerifyNow and PFA-100 compared with cilostazol. However, there were favorable changes in atherogenic dyslipidemia only in the cilostazol.

Diabetes, Obesity and Metabolism
The Presence of Clonal Hematopoiesis Is Negatively Associated with Diabetic Peripheral Neuropathy in Type 2 Diabetes: Tae Jung Oh, Han Song, Youngil Koh, Sung Hee Choi; Endocrinol Metab. 2022;37(2):243-248. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1337

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Background
Clonal hematopoiesis of indeterminate potential (CHIP) has been reported to be associated with increased cardiovascular disease, aging and insulin resistance. Despite the debate of causal contribution of CHIP on metabolic diseases, we want to explore whether CHIP is related to diabetic peripheral neuropathy (DPN).
Methods
This study analyzed the prevalence of CHIP in patients with type 2 diabetes classified according to DPN status. Logistic regression analysis was used to evaluate the association between CHIP and DPN.
Results
CHIP was more prevalent in subjects without DPN than those with DPN (19.9% vs. 8.8%, respectively; P=0.013). Individuals having any CHIP, or DNA methyltransferase 3A (DNMT3A) CHIP were less likely to have any abnormality shown in DPN test; the adjusted odds ratio were 0.85 (95% confidence interval [CI], 0.73 to 1.00) and 0.70 (95% CI, 0.56 to 0.89), respectively. Interestingly, DNMT3A CHIP showed the negative association, but Tet methylcytosine dioxygenase 2 (TET2) CHIP showed the positive association with abnormal feet electrochemical skin conductance level.
Conclusion
On the contrary to expectations, CHIP was negatively associated with DPN. Functional linking between the mutation in hematopoietic cells and DPN, and the opposite role of DNMT3A and TET2 should be investigated.

Citations

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TET2 mutation as prototypic clonal hematopoiesis lesion
Luca Guarnera, Babal K. Jha
Seminars in Hematology.2024; 61(1): 51. CrossRef
Clonal hematopoiesis with DNMT3A mutation is associated with lower white matter hyperintensity volume
Woo‐Jin Lee, Keun‐Hwa Jung, Han Song, Heesun Lee, Hyo Eun Park, Youngil Koh, Su‐Yeon Choi, Kyung‐Il Park
CNS Neuroscience & Therapeutics.2023; 29(5): 1243. CrossRef

Diabetes, Obesity and Metabolism
Associations of Phthalate Metabolites and Bisphenol A Levels with Obesity in Children: The Korean National Environmental Health Survey (KoNEHS) 2015 to 2017: Moon Young Seo, Shinje Moon, Shin-Hye Kim, Mi Jung Park; Endocrinol Metab. 2022;37(2):249-260. Published online April 7, 2022; DOI: https://doi.org/10.3803/EnM.2021.1235

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Background
Phthalates and bisphenol A (BPA) are synthetic chemicals widely used in daily life. This study investigated urinary phthalate and BPA levels in Korean children and their associations with obesity. Methods: A total of 2,351 children aged 3 to 17 years who participated in the Korean National Environmental Health Survey 2015 to 2017 were included. Urinary dilution was corrected using covariate-adjusted standardization (CAS). We examined the geometric mean (GM) concentrations of urinary phthalate metabolites, including di (2-ethylhexyl) phthalate (DEHP) metabolites (mono [2-ethyl-5-hydroxyhexyl] phthalate, mono [2-ethyl-5-oxohexyl] phthalate, and mono [2-ethyl-5-carboxypentyl] phthalate [MECPP]), mono-benzyl-phthalate (MBzP), mono (carboxyoctyl) phthalate (MCOP), mono (carboxy-isononyl) phthalate (MCNP), mono (3-carboxypropyl) phthalate, and mono-n-butyl-phthalate (MnBP), and BPA. We also analyzed the odds ratio (OR) for obesity according to the quartiles of each analyte. Results: The urinary GM levels of DEHP metabolites and MnBP were notably higher among Korean children than among American, Canadian, and German children. The CAS-applied GM concentrations of most analytes, except for MBzP, MCOP, and MCNP, were higher in children aged 3 to 5 years than in those aged 6 to 17 years. The OR for obesity in the highest quartile of MECPP was significantly higher than in the lowest quartile after adjusting for covariates. However, the other phthalate metabolites and BPA were not significantly associated with obesity. Conclusion: The concentrations of urinary DEHP metabolites and MnBP were higher in Korean children than in children in Western countries. Urinary MECPP exposure, but not other phthalates or BPA, showed a positive association with obesity in Korean children. Further studies are required to elucidate the causal relationships.

Citations

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Diethyl phthalate, a plasticizer, induces adipocyte inflammation and apoptosis in mice after long‐term dietary administration
Shirsha Mondal, Soumyadeep Basu, Songita Ghosh, Suktara Guria, Sutapa Mukherjee
Journal of Biochemical and Molecular Toxicology.2024;[Epub] CrossRef
Urinary concentrations of phthalate/DINCH metabolites and body mass index among European children and adolescents in the HBM4EU Aligned Studies: A cross-sectional multi-country study
Anteneh Desalegn, Tessa Schillemans, Eleni Papadopoulou, Amrit K. Sakhi, Line S. Haug, Ida Henriette Caspersen, Andrea Rodriguez-Carrillo, Sylvie Remy, Greet Schoeters, Adrian Covaci, Michelle Laeremans, Mariana F Fernández, Susana Pedraza-Diaz, Tina Kold
Environment International.2024; 190: 108931. CrossRef
Associations of prenatal and concurrent exposure to phenols mixture with anthropometric measures and blood pressure during childhood: A time-varying mixture approach
Yiming Dai, Jiayun Ding, Zheng Wang, Boya Zhang, Qin Guo, Jianqiu Guo, Xiaojuan Qi, Dasheng Lu, Xiuli Chang, Chunhua Wu, Jiming Zhang, Zhijun Zhou
Environmental Research.2024; 261: 119766. CrossRef
Dietary bisphenols exposure as an influencing factor of body mass index
Yolanda Gálvez-Ontiveros, Celia Monteagudo, María Giles-Mancilla, José Joaquín Muros, Vega Almazán, María Alba Martínez-Burgos, Cristina Samaniego-Sánchez, Inmaculada Salcedo-Bellido, Ana Rivas, Alberto Zafra-Gómez
Environmental Health.2024;[Epub] CrossRef
Endocrine-Disrupting Compounds in Urban Soils of Malaysia: Occurrence, Contamination, and Impacts on Health and the Environment
Michael Lie, Joseph Kasongo, Elias Mtui, Rubiyatno, Jovale Vincent Tongco
Tropical Aquatic and Soil Pollution.2024;[Epub] CrossRef
Problematic issues of the impact of microplastics on the human body and the environment: A review
Viktoria V. Pupykina, Irina N. Zakharova
Pediatrics. Consilium Medicum.2024; (3): 230. CrossRef
Di(2-ethylhexyl)phthalate and type 2 diabetes
Sebolaishi Doris Makhubela, Ananias Hodi Kgopa, Matlou Phineas Mokgotho, Leshweni Jerry Shai
Environmental Science: Advances.2024;[Epub] CrossRef
Nontargeted metabolomic evidence for antagonism between tetracycline and its resistance bacteria underlying their obesogenic effects on Caenorhabditis elegans
Zhuo Li, Di Wu, Zhenyang Yu, Changzheng Cui, Daqiang Yin
Science of The Total Environment.2023; 859: 160223. CrossRef
Prospective association between phthalate exposure in childhood and liver function in adolescence: the Ewha Birth and Growth Cohort Study
Seonhwa Lee, Hye Ah Lee, Bohyun Park, Hyejin Han, Young Sun Hong, Eun Hee Ha, Hyesook Park
Environmental Health.2023;[Epub] CrossRef
Bisphenol A substitutes and childhood obesity at 7 years: a cross-sectional study in Shandong, China
Minyan Chen, Cheng Lv, Shanyu Zhang, Lap Ah Tse, Xinyu Hong, Xi Liu, Yu Ding, Ping Xiao, Ying Tian, Yu Gao
Environmental Science and Pollution Research.2023; 30(29): 73174. CrossRef
Association between Di-2-ethylhexyl phthalate and nonalcoholic fatty liver disease among US adults: Mediation analysis of body mass index and waist circumference in the NHANES
Youming He, Jun Zou, Ting Hong, Dan Feng
Food and Chemical Toxicology.2023; 179: 113968. CrossRef
Association between phthalate exposure and obesity risk: A meta-analysis of observational studies
Qian Wu, Gang Li, Chen-Yang Zhao, Xiao-Lin Na, Yun-Bo Zhang
Environmental Toxicology and Pharmacology.2023; 102: 104240. CrossRef
Levels of Bisphenol A and its analogs in nails, saliva, and urine of children: a case control study
Yolanda Gálvez-Ontiveros, Inmaculada Moscoso-Ruiz, Vega Almazán Fernández de Bobadilla, Celia Monteagudo, Rafael Giménez-Martínez, Lourdes Rodrigo, Alberto Zafra-Gómez, Ana Rivas
Frontiers in Nutrition.2023;[Epub] CrossRef
Nontargeted Metabolomic Evidence for Antagonism between Tetracycline and its Resistance Bacteria Underlying Their Obesogenic Effects on Caenorhabditis Elegans
Zhuo Li, Zhenyang Yu, Changzheng Cui, Daqiang Yin
SSRN Electronic Journal .2022;[Epub] CrossRef

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Association of High-Density Lipoprotein Cholesterol Phenotypes with the Risk of Cardiovascular Diseases and Mortality: A Cohort Study in Korea: Ga Eun Nam, Youn Huh, Jin-Hyung Jung, Kyungdo Han, Seon Mee Kim, on Behalf of the Taskforce Team of the Obesity Fact Sheet of the Korean Society for the Study of Obesity; Endocrinol Metab. 2022;37(2):261-271. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1259

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Background
We investigated whether low high-density lipoprotein cholesterol (HDL-C) and isolated and non-isolated low HDL-C levels are associated with the risk of cardiovascular diseases and all-cause mortality among Korean adults.
Methods
We included 8,665,841 individuals aged ≥20 years who had undergone a health examination provided by the Korean National Health Insurance Service (NHIS) in 2009 and were followed up until the end of 2018. The hazard ratios (HRs) and 95% confidence intervals (CIs) for study outcomes were calculated using multivariable Cox proportional hazard regression analysis.
Results
During the 8.2 years of mean follow-up, myocardial infarction (MI), stroke, and all-cause mortality occurred in 81,431, 110,996, and 244,309 individuals, respectively. After adjusting for confounding variables (model 3), individuals with low HDL-C and lower HDL quartiles were associated with significantly increased risks of all three outcomes, compared to those with normal HDL-C and highest HDL-C quartile (all P<0.001), respectively. HRs for incident MI (1.28; 95% CI, 1.26 to 1.30), stroke (1.13; 95% CI, 1.11 to 1.15), and all-cause mortality (1.07; 95% CI, 1.05 to 1.08) increased in the non-isolated low HDL-C group compared to the normal HDL-C group. Isolated low HDL-C also showed an increase in the HRs of incident stroke (1.06; 95% CI, 1.04 to 1.08) and all-cause mortality (1.30; 95% CI, 1.28 to 1.32).
Conclusion
Low HDL-C and non-isolated low HDL-C were associated with increased risk of MI, stroke, and all-cause mortality, and isolated low HDL-C was associated with incident stroke and all-cause mortality risk.

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Association between HDL levels and stroke outcomes in the Arab population
Aizaz Ali, Omar Obaid, Naveed Akhtar, Rahul Rao, Syed Haroon Tora, Ashfaq Shuaib
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Association of adiposity and fitness with triglyceride-to-high-density lipoprotein cholesterol ratio in youth
Danladi Ibrahim Musa, Abel Lamina Toriola, Nurudeen O Abubakar, Sunday Omachi, Victor B Olowoleni, Kolade B Ayodele
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Association between cholesterol levels and dementia risk according to the presence of diabetes and statin use: a nationwide cohort study
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Scientific Reports.2022;[Epub] CrossRef

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Cumulative Exposure to High γ-Glutamyl Transferase Level and Risk of Diabetes: A Nationwide Population-Based Study: Ji-Yeon Park, Kyungdo Han, Hun-Sung Kim, Jae-Hyoung Cho, Kun-Ho Yoon, Mee Kyoung Kim, Seung-Hwan Lee; Endocrinol Metab. 2022;37(2):272-280. Published online April 13, 2022; DOI: https://doi.org/10.3803/EnM.2022.1416

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Background
Elevated γ-glutamyl transferase (γ-GTP) level is associated with metabolic syndrome, impaired glucose tolerance, and insulin resistance, which are risk factors for type 2 diabetes. We aimed to investigate the association of cumulative exposure to high γ-GTP level with risk of diabetes.
Methods
Using nationally representative data from the Korean National Health Insurance system, 346,206 people who were free of diabetes and who underwent 5 consecutive health examinations from 2005 to 2009 were followed to the end of 2018. High γ-GTP level was defined as those in the highest quartile, and the number of exposures to high γ-GTP level ranged from 0 to 5. Hazard ratio (HR) and 95% confidence interval (CI) for diabetes were analyzed using the multivariable Cox proportional-hazards model.
Results
The mean follow-up duration was 9.2±1.0 years, during which 15,183 (4.4%) patients developed diabetes. There was a linear increase in the incidence rate and the risk of diabetes with cumulative exposure to high γ-GTP level. After adjusting for possible confounders, the HR of diabetes in subjects with five consecutive high γ-GTP levels were 2.60 (95% CI, 2.47 to 2.73) in men and 3.05 (95% CI, 2.73 to 3.41) in women compared with those who never had a high γ-GTP level. Similar results were observed in various subgroup and sensitivity analyses.
Conclusion
There was a linear relationship between cumulative exposure to high γ-GTP level and risk of diabetes. Monitoring and lowering γ-GTP level should be considered for prevention of diabetes in the general population.

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Validation of Estimated Small Dense Low-Density Lipoprotein Cholesterol Concentration in a Japanese General Population
Keisuke Endo, Ryo Kobayashi, Makito Tanaka, Marenao Tanaka, Yukinori Akiyama, Tatsuya Sato, Itaru Hosaka, Kei Nakata, Masayuki Koyama, Hirofumi Ohnishi, Satoshi Takahashi, Masato Furuhashi
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Risk Factors for Colorectal Adenoma and Cancer in Comprehensive Health Checkups: Usefulness of Gamma-Glutamyltransferase
Yoko Yamanouchi, Maiko Osawa, Takaaki Senbonmatsu, Yuki Shiko, Yohei Kawasaki, Toshihiro Muramatsu
Journal of Personalized Medicine.2024; 14(11): 1082. CrossRef
Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study
Han-Sang Baek, Bongseong Kim, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Sang-Ah Chang, Kyungdo Han, Jae-Seung Yun
Endocrinology and Metabolism.2023; 38(6): 770. CrossRef
Elevated gamma‐glutamyl transferase to high‐density lipoprotein cholesterol ratio has a non‐linear association with incident diabetes mellitus: A second analysis of a cohort study
Haofei Hu, Yong Han, Mijie Guan, Ling Wei, Qijun Wan, Yanhua Hu
Journal of Diabetes Investigation.2022; 13(12): 2027. CrossRef
Gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio: A valuable predictor of type 2 diabetes mellitus incidence
Wangcheng Xie, Bin Liu, Yansong Tang, Tingsong Yang, Zhenshun Song
Frontiers in Endocrinology.2022;[Epub] CrossRef

Thyroid Big Data Articles (National Health Insurance Service Database)
Graves’ Disease and the Risk of End-Stage Renal Disease: A Korean Population-Based Study: Yoon Young Cho, Bongseong Kim, Dong Wook Shin, Hye Ryoun Jang, Bo-Yeon Kim, Chan-Hee Jung, Jae Hyeon Kim, Sun Wook Kim, Jae Hoon Chung, Kyungdo Han, Tae Hyuk Kim; Endocrinol Metab. 2022;37(2):281-289. Published online April 6, 2022; DOI: https://doi.org/10.3803/EnM.2021.1333

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Background
Hyperthyroidism is associated with an increased glomerular filtration rate (GFR) in the hyperdynamic state, which is reversible after restoring euthyroidism. However, long-term follow-up of renal dysfunction in patients with hyperthyroidism has not been performed.
Methods
This was a retrospective cohort study using the Korean National Health Insurance database and biannual health checkup data. We included 41,778 Graves’ disease (GD) patients and 41,778 healthy controls, matched by age and sex. The incidences of end-stage renal disease (ESRD) were calculated in GD patients and controls. The cumulative dose and duration of antithyroid drugs (ATDs) were calculated for each patient and categorized into the highest, middle, and lowest tertiles.
Results
Among 41,778 GD patients, 55 ESRD cases occurred during 268,552 person-years of follow-up. Relative to the controls, regardless of smoking, drinking, or comorbidities, including chronic kidney disease, GD patients had a 47% lower risk of developing ESRD (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37 to 0.76). In particular, GD patients with a higher baseline GFR (≥90 mL/min/1.73 m2; HR, 0.33; 95% CI, 0.11 to 0.99), longer treatment duration (>33 months; HR, 0.31; 95% CI, 0.17 to 0.58) or higher cumulative dose (>16,463 mg; HR, 0.29; 95% CI, 0.15 to 0.57) of ATDs had a significantly reduced risk of ESRD.
Conclusion
This was the first epidemiological study on the effect of GD on ESRD, and we demonstrated that GD population had a reduced risk for developing ESRD.

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Renal function changes in patients with subclinical hyperthyroidism: a novel postulated mechanism
Magdy Mohamed Allam, Hanaa Tarek El-Zawawy, Tarek Hussein El-Zawawy
Endocrine.2023; 82(1): 78. CrossRef
Effect of Hyperthyroidism on Preventing Renal Insufficiency
Tae Yong Kim
Endocrinology and Metabolism.2022; 37(2): 220. CrossRef
Effects and Clinical Value of Peritoneal Dialysis on Water and Water Balance, Adverse Reactions, Quality of Life, and Clinical Prognosis in Patients with Decompensated Chronic Nephropathy: A Systematic Review and Meta-Analysis
Xichao Wang, Miaomiao Zhang, Na Sun, Wenxiu Chang, Gang Chen
Computational and Mathematical Methods in Medicine.2022; 2022: 1. CrossRef

Thyroid
Developmental Hypothyroidism Influences the Development of the Entorhinal-Dentate Gyrus Pathway of Rat Offspring: Ting Jin, Ranran Wang, Shiqiao Peng, Xin Liu, Hanyi Zhang, Xue He, Weiping Teng, Xiaochun Teng; Endocrinol Metab. 2022;37(2):290-302. Published online April 8, 2022; DOI: https://doi.org/10.3803/EnM.2021.1343

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Background
Developmental hypothyroidism impairs learning and memory in offspring, which depend on extensive neuronal circuits in the entorhinal cortex, together with the hippocampus and neocortex. The entorhinal-dentate gyrus pathway is the main entrance of memory circuits. We investigated whether developmental hypothyroidism impaired the morphological development of the entorhinal-dentate gyrus pathway.
Methods
We examined the structure and function of the entorhinal-dentate gyrus pathway in response to developmental hypothyroidism induced using 2-mercapto-1-methylimidazole.
Results
1,1´-Dioctadecyl-3,3,3´,3´-tetramethylindocarbocyanine perchlorate tract tracing indicated that entorhinal axons showed delayed growth in reaching the outer molecular layer of the dentate gyrus at postnatal days 2 and 4 in hypothyroid conditions. The proportion of fibers in the outer molecular layer was significantly smaller in the hypothyroid group than in the euthyroid group at postnatal day 4. At postnatal day 10, the pathway showed a layer-specific distribution in the outer molecular layer, similar to the euthyroid group. However, the projected area of entorhinal axons was smaller in the hypothyroid group than in the euthyroid group. An electrophysiological examination showed that hypothyroidism impaired the long-term potentiation of the perforant and the cornu ammonis 3–cornu ammonis 1 pathways. Many repulsive axon guidance molecules were involved in the formation of the entorhinaldentate gyrus pathway. The hypothyroid group had higher levels of erythropoietin-producing hepatocyte ligand A3 and semaphorin 3A than the euthyroid group.
Conclusion
We demonstrated that developmental hypothyroidism might influence the development of the entorhinal-dentate gyrus pathway, contributing to impaired long-term potentiation. These findings improve our understanding of neural mechanisms for memory function.

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Semaphorin 3A Increases in the Plasma of Women with Diminished Ovarian Reserve Who Respond Better to Controlled Ovarian Stimulation
Michela Palese, Gabriella Ferretti, Giuseppe Perruolo, Sara Serafini, Rossana Sirabella, Vincenzo Marrone, Martina De Rosa, Laura Sarno, Ida Strina, Carmela Matrone, Maurizio Guida
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Thyroid Big Data Articles (National Health Insurance Service Database)
Repeated Low High-Density Lipoprotein Cholesterol and the Risk of Thyroid Cancer: A Nationwide Population- Based Study in Korea: Jinyoung Kim, Mee Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Kyungdo Han, Hyuk-Sang Kwon; Endocrinol Metab. 2022;37(2):303-311. Published online April 6, 2022; DOI: https://doi.org/10.3803/EnM.2021.1332

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Background
High-density lipoprotein cholesterol (HDL-C) plays an important role in the reverse cholesterol transport pathway and prevents atherosclerosis-mediated disease. It has also been suggested that HDL-C may be a protective factor against cancer. However, an inverse correlation between HDL-C and cancer has not been established, and few studies have explored thyroid cancer.
Methods
The study participants received health checkups provided by the Korean National Health Insurance Service from 2009 to 2013 and were followed until 2019. Considering the variability of serum HDL-C level, low HDL-C level was analyzed by grouping based on four consecutive health checkups. The data analysis was performed using univariate and multivariate Cox proportional hazard regression models.
Results
A total of 3,134,278 total study participants, thyroid cancer occurred in 16,129. In the crude model, the hazard ratios for the association between repeatedly measured low HDL-C levels and thyroid cancer were 1.243, 1.404, 1.486, and 1.680 (P for trend <0.01), respectively, which were significant even after adjusting for age, sex, lifestyle factors, and metabolic diseases. The subgroup analysis revealed that low HDL-C levels likely had a greater impact on the group of patients with central obesity (P for interaction= 0.062), high blood pressure (P for interaction=0.057), impaired fasting glucose (P for interaction=0.051), and hyperlipidemia (P for interaction=0.126).
Conclusion
Repeatedly measured low HDL-C levels can be considered a risk factor for cancer as well as vascular disease. Low HDL-C levels were associated with the risk of thyroid cancer, and this correlation was stronger in a metabolically unhealthy population.

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Jianning Liu, Zhuoying Feng, Ru Gao, Peng Liu, Fangang Meng, Lijun Fan, Lixiang Liu, Yang Du
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Carbohydrate, Lipid, and Apolipoprotein Biomarkers in Blood and Risk of Thyroid Cancer: Findings from the AMORIS Cohort
Xue Xiao, Yi Huang, Fetemeh Sadeghi, Maria Feychting, Niklas Hammar, Fang Fang, Zhe Zhang, Qianwei Liu
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Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
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Meijuan Tan, Shijie Yang, Xiequn Xu
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Rui Gao, Kaixin Du, Jinhua Liang, Yi Xia, Jiazhu Wu, Yue Li, Bihui Pan, Li Wang, Jianyong Li, Wei Xu
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Weiwei Liang, FangFang Sun
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Qiang Ma, Yu Li, Lijuan An, Liang Guo, Xiaokang Liu
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Xiaowen Zhang, Yuyang Ze, Jianfeng Sang, Xianbiao Shi, Yan Bi, Shanmei Shen, Xinlin Zhang, Dalong Zhu
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Thyroid
Immunoglobulin G4-Related Thyroid Disease: A Single-Center Experience and Literature Review: Meihua Jin, Bictdeun Kim, Ahreum Jang, Min Ji Jeon, Young Jun Choi, Yu-Mi Lee, Dong Eun Song, Won Gu Kim; Endocrinol Metab. 2022;37(2):312-322. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1318

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Background
Immunoglobulin G4 (IgG4)-related disease is an entity that can involve the thyroid gland. The spectrum of IgG4-related thyroid disease (IgG4-RTD) includes Hashimoto thyroiditis (HT) and its fibrotic variant, Riedel thyroiditis, as well as Graves’ disease. The early diagnosis of IgG4-RTD is important because it is a medically treatable disease, and a delay in the diagnosis might result in unnecessary surgery. We present a case series of IgG4-RTD with a review of the literature.
Methods
We retrospectively reviewed the clinical presentation and the radiological and pathological findings of patients diagnosed with IgG4-RTD between 2017 and 2021 at a tertiary medical center in Korea. We also conducted a literature review of IgG4-RTD.
Results
Five patients were diagnosed with IgG4-RTD during the study period. The patients’ age ranged from 31 to 76 years, and three patients were men. Most patients visited the clinic for a neck mass, and hypoechogenic nodular lesions were observed on neck ultrasonography. Three patients had IgG4 HT, and two patients had IgG4 Riedel thyroiditis. All patients developed hypothyroidism that necessitated L-thyroxine replacement. The diagnosis of IgG4-RTD was confirmed after a pathological examination of the surgical specimen in the first two cases. However, the early diagnosis was possible after a core needle biopsy in three clinically suspected patients.
Conclusion
The diagnosis of IgG4-RTD requires clinical suspicion combined with serology and histological analyses using IgG4 immunostaining. The early diagnosis of IgG4-RTD is difficult; thus, biopsy with IgG4 immunostaining and serum IgG4 measurements will help diagnose patients suspected of having IgG4-RTD.

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Are sonographic characteristics of Hashimoto’s thyroiditis related with immunologic parameters? A cross-sectional study
K. Kenarlı, A. B. Bahçecioğlu, Ö. B. Aksu, S. Güllü
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A machine learning-based diagnosis modeling of IgG4 Hashimoto’s thyroiditis
Chenxu Zhao, Zhiming Sun, Yang Yu, Yiwei Lou, Liyuan Liu, Ge Li, Jumei Liu, Lei Chen, Sainan Zhu, Yu Huang, Yang Zhang, Ying Gao
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Thyroid
Usefulness of Real-Time Quantitative Microvascular Ultrasonography for Differentiation of Graves’ Disease from Destructive Thyroiditis in Thyrotoxic Patients: Han-Sang Baek, Ji-Yeon Park, Chai-Ho Jeong, Jeonghoon Ha, Moo Il Kang, Dong-Jun Lim; Endocrinol Metab. 2022;37(2):323-332. Published online April 13, 2022; DOI: https://doi.org/10.3803/EnM.2022.1413

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Background
Microvascular ultrasonography (MVUS) is a third-generation Doppler technique that was developed to increase sensitivity compared to conventional Doppler. The purpose of this study was to compare MVUS with conventional color Doppler (CD) and power Doppler (PD) imaging to distinguish Graves’ disease (GD) from destructive thyroiditis (DT).
Methods
This prospective study included 101 subjects (46 GDs, 47 DTs, and eight normal controls) from October 2020 to November 2021. All ultrasonography examinations were performed using microvascular flow technology (MV-Flow). The CD, PD, and MVUS images were semi-quantitatively graded according to blood flow patterns. On the MVUS images, vascularity indices (VIs), which were the ratio (%) of color pixels in the total grayscale pixels in a defined region of interest, were obtained automatically. Receiver operating characteristic curve analysis was performed to verify the diagnostic performance of MVUS. The interclass correlation coefficient and Cohen’s kappa analysis were used to analyze the reliability of MVUS (ClinicalTrials.gov:NCT04879173).
Results
The area under the curve (AUC) for CD, PD, MVUS, and MVUS-VI was 0.822, 0.844, 0.808, and 0.852 respectively. The optimal cutoff value of the MVUS-VI was 24.95% for distinguishing GD and DT with 87% sensitivity and 80.9% specificity. We found a significant positive correlation of MVUS-VI with thyrotropin receptor antibody (r=0.554) and with thyroid stimulating immunoglobulin bioassay (r=0.841). MVUS showed high intra- and inter-observer reliability from various statistical method.
Conclusion
In a real time and quantitative manner, MVUS-VI could be helpful to differentiate GD from thyroiditis in thyrotoxic patients, with less inter-observer variability.

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The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves’ Disease
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Duplex Hemodynamic Parameters of Both Superior and Inferior Thyroid Arteries in Evaluation of Thyroid Hyperfunction Disorders
Maha Assem Hussein, Alaa Abdel Hamid, Rasha M Abdel Samie, Elshaymaa Hussein, Shereen Sadik Elsawy
International Journal of General Medicine.2022; Volume 15: 7131. CrossRef
Case 5: A 41-Year-Old Woman With Palpitation
Jiwon Yang, Kabsoo Shin, Jeongmin Lee, Jeonghoon Ha, Dong-Jun Lim, Han-Sang Baek
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Guillaume Goudot, Yanis Berkane, Eloi de Clermont-Tonnerre, Claire Guinier, Irina Filz von Reiterdank, Antonia van Kampen, Korkut Uygun, Curtis L. Cetrulo, Basak E. Uygun, Anahita Dua, Alexandre G. Lellouch
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