Endocrinology and Metabolism

Hyun Jin Kim (Kim HJ)

16 Articles

Diabetes, Obesity and Metabolism
Expression of LONP1 Is High in Visceral Adipose Tissue in Obesity, and Is Associated with Glucose and Lipid Metabolism: Ju Hee Lee, Saet-Byel Jung, Seong Eun Lee, Ji Eun Kim, Jung Tae Kim, Yea Eun Kang, Seul Gi Kang, Hyon-Seung Yi, Young Bok Ko, Ki Hwan Lee, Bon Jeong Ku, Minho Shong, Hyun Jin Kim; Endocrinol Metab. 2021;36(3):661-671. Published online June 22, 2021; DOI: https://doi.org/10.3803/EnM.2021.1023

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Background
The nature and role of the mitochondrial stress response in adipose tissue in relation to obesity are not yet known. To determine whether the mitochondrial unfolded protein response (UPR^mt) in adipose tissue is associated with obesity in humans and rodents.
Methods
Visceral adipose tissue (VAT) was obtained from 48 normoglycemic women who underwent surgery. Expression levels of mRNA and proteins were measured for mitochondrial chaperones, intrinsic proteases, and components of electron-transport chains. Furthermore, we systematically analyzed metabolic phenotypes with a large panel of isogenic BXD inbred mouse strains and Genotype-Tissue Expression (GTEx) data.
Results
In VAT, expression of mitochondrial chaperones and intrinsic proteases localized in inner and outer mitochondrial membranes was not associated with body mass index (BMI), except for the Lon protease homolog, mitochondrial, and the corresponding gene LONP1, which showed high-level expression in the VAT of overweight or obese individuals. Expression of LONP1 in VAT positively correlated with BMI. Analysis of the GTEx database revealed that elevation of LONP1 expression is associated with enhancement of genes involved in glucose and lipid metabolism in VAT. Mice with higher Lonp1 expression in adipose tissue had better systemic glucose metabolism than mice with lower Lonp1 expression.
Conclusion
Expression of mitochondrial LONP1, which is involved in the mitochondrial quality control stress response, was elevated in the VAT of obese individuals. In a bioinformatics analysis, high LONP1 expression in VAT was associated with enhanced glucose and lipid metabolism.

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LONP1 ameliorates liver injury and improves gluconeogenesis dysfunction in acute-on-chronic liver failure
Muchen Wu, Jing Wu, Kai Liu, Minjie Jiang, Fang Xie, Xuehong Yin, Jushan Wu, Qinghua Meng
Chinese Medical Journal.2024; 137(2): 190. CrossRef
Mitochondrial quality control proteases and their modulation for cancer therapy
Jiangnan Zhang, Wenliang Qiao, Youfu Luo
Medicinal Research Reviews.2023; 43(2): 399. CrossRef
Effects of Obesity and Calorie Restriction on Cancer Development
Ekaterina Sergeeva, Tatiana Ruksha, Yulia Fefelova
International Journal of Molecular Sciences.2023; 24(11): 9601. CrossRef
Mitochondrial Dysfunction Associated with mtDNA in Metabolic Syndrome and Obesity
Natalia Todosenko, Olga Khaziakhmatova, Vladimir Malashchenko, Kristina Yurova, Maria Bograya, Maria Beletskaya, Maria Vulf, Natalia Gazatova, Larisa Litvinova
International Journal of Molecular Sciences.2023; 24(15): 12012. CrossRef
Down‐regulation of Lon protease 1 lysine crotonylation aggravates mitochondrial dysfunction in polycystic ovary syndrome
Yuan Xie, Shuwen Chen, Zaixin Guo, Ying Tian, Xinyu Hong, Penghui Feng, Qiu Xie, Qi Yu
MedComm.2023;[Epub] CrossRef
The mitochondrial unfolded protein response: A multitasking giant in the fight against human diseases
Zixin Zhou, Yumei Fan, Ruikai Zong, Ke Tan
Ageing Research Reviews.2022; 81: 101702. CrossRef

Clinical Study
Genetic Analysis of CLCN7 in an Old Female Patient with Type II Autosomal Dominant Osteopetrosis: Seon Young Kim, Younghak Lee, Yea Eun Kang, Ji Min Kim, Kyong Hye Joung, Ju Hee Lee, Koon Soon Kim, Hyun Jin Kim, Bon Jeong Ku, Minho Shong, Hyon-Seung Yi; Endocrinol Metab. 2018;33(3):380-386. Published online September 18, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.3.380

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Background

Type II autosomal dominant osteopetrosis (ADO II) is a rare genetically heterogeneous disorder characterized by osteosclerosis and increased bone mass, predominantly involving spine, pelvis, and skull. It is closely related to functional defect of osteoclasts caused by chloride voltage-gated channel 7 (CLCN7) gene mutations. In this study, we aimed to identify the pathogenic mutation in a Korean patient with ADO II using whole exome sequencing.

Methods

We evaluated the clinical, biochemical, and radiographic analysis of a 68-year-old woman with ADO II. We also performed whole exome sequencing to identify pathogenic mutation of a rare genetic disorder of the skeleton. Moreover, a polymorphism phenotyping program, Polymorphism Phenotyping v2 (PolyPhen-2), was used to assess the effect of the identified mutation on protein function.

Results

Whole exome sequencing using peripheral leukocytes revealed a heterozygous c.296A>G missense mutation in the CLCN7 gene. The mutation was also confirmed using Sanger sequencing. The mutation c.296A>G was regarded to have a pathogenic effect by PolyPhen-2 software.

Conclusion

We detect a heterozygous mutation in CLCN7 gene of a patient with ADO II, which is the first report in Korea. Our present findings suggest that symptoms and signs of ADO II patient having a c.296A>G mutation in CLCN7 may appear at a very late age. The present study would also enrich the database of CLCN7 mutations and improve our understanding of ADO II.

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Autosomal dominant osteopetrosis type II resulting from a de novo mutation in the CLCN7 gene: A case report
Xiu-Li Song, Li-Yuan Peng, Dao-Wen Wang, Hong Wang
World Journal of Clinical Cases.2022; 10(20): 6936. CrossRef
Magnetic resonance findings in a Cavalier King Charles spaniel with osteopetrosis, Chiari‐like malformation and syringomyelia
Ricardo Fernandes, C J Jordan, Colin Driver
Veterinary Record Case Reports.2019;[Epub] CrossRef

Clinical Study
The Eosinophil Count Tends to Be Negatively Associated with Levels of Serum Glucose in Patients with Adrenal Cushing Syndrome: Younghak Lee, Hyon-Seung Yi, Hae Ri Kim, Kyong Hye Joung, Yea Eun Kang, Ju Hee Lee, Koon Soon Kim, Hyun Jin Kim, Bon Jeong Ku, Minho Shong; Endocrinol Metab. 2017;32(3):353-359. Published online September 18, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.3.353

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Background

Cushing syndrome is characterized by glucose intolerance, cardiovascular disease, and an enhanced systemic inflammatory response caused by chronic exposure to excess cortisol. Eosinopenia is frequently observed in patients with adrenal Cushing syndrome, but the relationship between the eosinophil count in peripheral blood and indicators of glucose level in patients with adrenal Cushing syndrome has not been determined.

Methods

A retrospective study was undertaken of the clinical and laboratory findings of 40 patients diagnosed with adrenal Cushing syndrome at Chungnam National University Hospital from January 2006 to December 2016. Clinical characteristics, complete blood cell counts with white blood cell differential, measures of their endocrine function, description of imaging studies, and pathologic findings were obtained from their medical records.

Results

Eosinophil composition and count were restored by surgical treatment of all of the patients with adrenal Cushing disease. The eosinophil count was inversely correlated with serum and urine cortisol, glycated hemoglobin, and inflammatory markers in the patients with adrenal Cushing syndrome.

Conclusion

Smaller eosinophil populations in patients with adrenal Cushing syndrome tend to be correlated with higher levels of blood sugar and glycated hemoglobin. This study suggests that peripheral blood eosinophil composition or count may be associated with serum glucose levels in patients with adrenal Cushing syndrome.

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Association between Eosinophil Count and Cortisol Concentrations in Equids Admitted in the Emergency Unit with Abdominal Pain
María Villalba-Orero, María Dolores Contreras-Aguilar, Jose Joaquín Cerón, Beatriz Fuentes-Romero, Marta Valero-González, María Martín-Cuervo
Animals.2024; 14(1): 164. CrossRef
Inverse relationship between eosinophil profiles and serum glucose concentration in dogs with naturally occurring hypercortisolism
Jimin Oh, Dohee Lee, Taesik Yun, Yoonhoi Koo, Yeon Chae, Mhan-Pyo Yang, Byeong-Teck Kang, Hakhyun Kim
Domestic Animal Endocrinology.2022; 80: 106727. CrossRef
Serum Cortisol and Its Correlation with Leucocyte Profile and Circulating Lipids in Donkeys (Equus asinus)
Daniela Alberghina, Alessandra Statelli, Vincenzo Monteverde, Irene Vazzana, Giuseppe Cascone, Michele Panzera
Animals.2022; 12(7): 841. CrossRef
Changes in leukocytes and CRP in different stages of major depression
Deepti Singh, Paul C. Guest, Henrik Dobrowolny, Veronika Vasilevska, Gabriela Meyer-Lotz, Hans-Gert Bernstein, Katrin Borucki, Alexandra Neyazi, Bernhard Bogerts, Roland Jacobs, Johann Steiner
Journal of Neuroinflammation.2022;[Epub] CrossRef
HIF1α is a direct regulator of steroidogenesis in the adrenal gland
Deepika Watts, Johanna Stein, Ana Meneses, Nicole Bechmann, Ales Neuwirth, Denise Kaden, Anja Krüger, Anupam Sinha, Vasileia Ismini Alexaki, Luis Gustavo Perez-Rivas, Stefan Kircher, Antoine Martinez, Marily Theodoropoulou, Graeme Eisenhofer, Mirko Peitz
Cellular and Molecular Life Sciences.2021; 78(7): 3577. CrossRef
The Immune System in Cushing’s Syndrome
Valeria Hasenmajer, Emilia Sbardella, Francesca Sciarra, Marianna Minnetti, Andrea M. Isidori, Mary Anna Venneri
Trends in Endocrinology & Metabolism.2020; 31(9): 655. CrossRef

Clinical Study
The Role of Circulating Slit2, the One of the Newly Batokines, in Human Diabetes Mellitus: Yea Eun Kang, Sorim Choung, Ju Hee Lee, Hyun Jin Kim, Bon Jeong Ku; Endocrinol Metab. 2017;32(3):383-388. Published online September 18, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.3.383

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Background

Slit2 is a new secreted protein from adipose tissue that improves glucose hemostasis in mice; however, there is no study about the serum levels and precise role of Slit2 in human. The aim of this study is to explore the serum level of Slit2 in human, and to identify the role of Slit2 in diabetes mellitus (DM).

Methods

The participants of this study consist of 38 subjects with newly diagnosed DM, and 75 healthy subjects as a control group. Serum Slit2 levels were measured using an enzyme-linked immunosorbent assay. Relationship between circulating Slit2 and diabetic related factors was investigated in diabetic group compared with non-diabetic group. Additionally, the correlations between the serum level of Slit2 and diverse metabolic parameters were analyzed.

Results

Circulating Slit2 level was more decreased in diabetic group than in control group, but there was no significant difference statistically. Interestingly, serum levels of Slit2 were significantly negatively correlated to the serum concentrations of fasting glucose (coefficient r=–0.246, P=0.008), the serum concentrations of postprandial glucose (coefficient r=–0.233, P=0.017), and glycosylated hemoglobin (HbA1c; coefficient r=–0.357, P<0.001).

Conclusion

From our study, the first report of circulating Slit2 levels in human, circulating Slit2 level significantly negatively correlated with serum glucose and HbA1c. Our results suggest that the circulating Slit2 may play a role in maintainence of glucose homeostasis in human, even though exact contribution and mechanism are not yet known.

Citations

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Brown adipose tissue-derived metabolites and their role in regulating metabolism
Khanyisani Ziqubu, Phiwayinkosi V. Dludla, Sihle E. Mabhida, Babalwa U. Jack, Susanne Keipert, Martin Jastroch, Sithandiwe E. Mazibuko-Mbeje
Metabolism.2024; 150: 155709. CrossRef
An update on the secretory functions of brown, white, and beige adipose tissue: Towards therapeutic applications
Zeinab Ghesmati, Mohsen Rashid, Shabnam Fayezi, Frank Gieseler, Effat Alizadeh, Masoud Darabi
Reviews in Endocrine and Metabolic Disorders.2024; 25(2): 279. CrossRef
The integrated bioinformatic analysis identifies immune microenvironment-related potential biomarkers for patients with gestational diabetes mellitus
Jie-ling Chen, Hui-fang Dai, Xin-chen Kan, Jie Wu, Hong-Wu Chen
Frontiers in Immunology.2024;[Epub] CrossRef
Adipokines from white adipose tissue in regulation of whole body energy homeostasis
Bijayashree Sahu, Naresh C. Bal
Biochimie.2023; 204: 92. CrossRef
The Role of Slit-2 in Gestational Diabetes Mellitus and Its Effect on Pregnancy Outcome
Yan Wang, Shihua Zhao, Wei Peng, Ying Chen, Jingwei Chi, Kui Che, Yangang Wang
Frontiers in Endocrinology.2022;[Epub] CrossRef
The Heartwarming Effect of Brown Adipose Tissue
Kelsey M. Pinckard, Kristin I. Stanford
Molecular Pharmacology.2022; 102(1): 39. CrossRef
New players of the adipose secretome: Therapeutic opportunities and challenges
Laetitia Coassolo, Niels Banhos Dannieskiold-Samsøe, Meng Zhao, Hobson Allen, Katrin J. Svensson
Current Opinion in Pharmacology.2022; 67: 102302. CrossRef
Serum CD14 concentration is associated with obesity and insulin resistance in non-diabetic individuals
Yea Eun Kang, Kyong Hye Joung, Ji Min Kim, Ju Hee Lee, Hyun Jin Kim, Bon Jeong Ku
Journal of International Medical Research.2022; 50(10): 030006052211300. CrossRef
Brown/Beige adipose tissues and the emerging role of their secretory factors in improving metabolic health: The batokines
Bilal Ahmad, Muhammad Sufyan Vohra, Mansab Ali Saleemi, Christopher J. Serpell, Isabel Lim Fong, Eng Hwa Wong
Biochimie.2021; 184: 26. CrossRef
Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential
Bruna B. Brandão, Ankita Poojari, Atefeh Rabiee
International Journal of Molecular Sciences.2021; 22(11): 5906. CrossRef
Brown Adipose Crosstalk in Tissue Plasticity and Human Metabolism
Camilla Scheele, Christian Wolfrum
Endocrine Reviews.2020; 41(1): 53. CrossRef
Development of a Cell-Based Assay for the Detection of Neutralizing Antibodies to PF-06730512 Using Homogenous Time-Resolved Fluorescence
Michael Luong, Ying Wang, Stephen P. Berasi, Janet E. Buhlmann, Hongying Yang, Boris Gorovits
The AAPS Journal.2020;[Epub] CrossRef
Brown and beige fat: From molecules to physiology and pathophysiology
Stefania Carobbio, Anne-Claire Guénantin, Isabella Samuelson, Myriam Bahri, Antonio Vidal-Puig
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids.2019; 1864(1): 37. CrossRef
Serum R-Spondin 1 Is a New Surrogate Marker for Obesity and Insulin Resistance
Yea Eun Kang, Ji Min Kim, Hyon-Seung Yi, Kyong Hye Joung, Ju Hee Lee, Hyun Jin Kim, Bon Jeong Ku
Diabetes & Metabolism Journal.2019; 43(3): 368. CrossRef
Deletion of Robo4 prevents high‐fat diet‐induced adipose artery and systemic metabolic dysfunction
Tam T. T. Phuong, Ashley E. Walker, Grant D. Henson, Daniel R. Machin, Dean Y. Li, Anthony J. Donato, Lisa A. Lesniewski
Microcirculation.2019;[Epub] CrossRef
Adipose Tissue-Derived Signatures for Obesity and Type 2 Diabetes: Adipokines, Batokines and MicroRNAs
Min-Woo Lee, Mihye Lee, Kyoung-Jin Oh
Journal of Clinical Medicine.2019; 8(6): 854. CrossRef
The role of brown and beige adipose tissue in glycaemic control
Katarina Klepac, Anastasia Georgiadi, Matthias Tschöp, Stephan Herzig
Molecular Aspects of Medicine.2019; 68: 90. CrossRef

Obesity and Metabolism
Plasma Adiponectin Levels in Elderly Patients with Prediabetes: Si Eun Kong, Yea Eun Kang, Kyong Hye Joung, Ju Hee Lee, Hyun Jin Kim, Bon Jeong Ku; Endocrinol Metab. 2015;30(3):326-333. Published online August 4, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.3.326

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Background

The significance of adiponectin levels in elderly individuals with prediabetes has yet to be determined. Thus, the present study was performed to evaluate the relationships between adiponectin levels and anthropometric variables, body composition parameters, insulin sensitivity, and lipid profiles in elderly prediabetic patients.

Methods

The present study included 120 subjects with prediabetes who were >65 years of age and were selected from among 1,993 subjects enrolled in the Korea Rural Genomic Cohort Study. All subjects underwent a 75 g oral glucose tolerance test and tests for measurement of insulin sensitivity. All diagnoses of prediabetes satisfied the criteria of the American Diabetes Association.

Results

Plasma adiponectin levels were lower in elderly prediabetic subjects than elderly subjects with normal glucose tolerance (P<0.01) as well as in elderly prediabetic patients with metabolic syndrome (MetS) than in those without MetS (P<0.02). When the subjects were categorized into two groups according to plasma adiponectin levels, the waist-to-hip ratio and 2-hour insulin levels were significantly lower in individuals with high plasma adiponectin levels than in those with low plasma adiponectin levels. Additionally, the plasma adiponectin levels of elderly prediabetic subject were inversely correlated with body mass index (BMI), waist circumference (WC), waist-to-hip ratio, visceral fat, visceral fat ratio, and 2-hour insulin levels.

Conclusion

The present findings demonstrated that the major factors correlated with adiponectin levels in elderly prediabetic subjects were BMI, WC, waist-to-hip ratio, visceral fat, visceral fat ratio, and 2-hour insulin levels.

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Differential Association of Selected Adipocytokines, Adiponectin, Leptin, Resistin, Visfatin and Chemerin, with the Pathogenesis and Progression of Type 2 Diabetes Mellitus (T2DM) in the Asir Region of Saudi Arabia: A Case Control Study
Mohammad Muzaffar Mir, Rashid Mir, Mushabab Ayed Abdullah Alghamdi, Javed Iqbal Wani, Zia Ul Sabah, Mohammed Jeelani, Vijaya Marakala, Shahzada Khalid Sohail, Mohamed O’haj, Muffarah Hamid Alharthi, Mohannad Mohammad S. Alamri
Journal of Personalized Medicine.2022; 12(5): 735. CrossRef
Postloading insulinemia is independently associated with arterial stiffness in young Japanese persons
Norimitsu Murai, Naoko Saito, Sayuri Nii, Yuto Nishikawa, Asami Suzuki, Eriko Kodama, Tatsuya Iida, Kentaro Mikura, Hideyuki Imai, Mai Hashizume, Yasuyoshi Kigawa, Rie Tadokoro, Chiho Sugisawa, Kei Endo, Toru Iizaka, Fumiko Otsuka, Shun Ishibashi, Shoichi
Hypertension Research.2021; 44(11): 1515. CrossRef
Association of Adiponectin and rs1501299 of the ADIPOQ Gene with Prediabetes in Jordan
Mahmoud Alfaqih, Faheem Al-Mughales, Othman Al-Shboul, Mohammad Al Qudah, Yousef Khader, Muhammad Al-Jarrah
Biomolecules.2018; 8(4): 117. CrossRef

Bone Metabolism
A Novel PHEX Gene Mutation in a Patient with Sporadic Hypophosphatemic Rickets: Yea Eun Kang, Jun Hwa Hong, Jimin Kim, Kyong Hye Joung, Hyun Jin Kim, Bon Jeong Ku, Koon Soon Kim; Endocrinol Metab. 2014;29(2):195-201. Published online June 26, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.2.195

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Phosphate regulating gene with homologies to endopeptidases on the X-chromosome (PHEX) is a common cause of X-linked hypophosphatemic (XLH) rickets. Diverse PHEX gene mutations have been reported; however, gene mutations in sporadic rickets are less common than in XLH rickets. Herein, we describe a 50-year-old female patient with sporadic hypophosphatemic rickets harboring a novel splicing-site mutation in the PHEX gene (c.663+1G>A) at the exon 5-intron 5 boundary. The patient had recently suffered from right thigh pain and an aggravated waddling gait. She also presented with very short stature, generalized bone pain, and muscle weakness. Despite low serum phosphate levels, her phosphate reabsorption rate was lower than normal. Additionally, her 1,25-dihydroxyvitamin D₃ concentration was lower than normal, although FGF23 level was normal. After treatment with alfacalcidol and elemental phosphate, her rachitic symptoms subsided, and callus formation was observed in the fracture site on the right femur.

Citations

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A pathogenic PHEX variant (c.1483-1G>C) in a Korean patient with X-linked hypophosphatemic rickets
In Hwa Jeong, Jae-Ho Yoo, Namhee Kim
Annals of Pediatric Endocrinology & Metabolism.2021; 26(2): 130. CrossRef
A novel de novo mosaic mutation in PHEX in a Korean patient with hypophosphatemic rickets
Misun Yang, Jinsup Kim, Aram Yang, Jahyun Jang, Tae Yeon Jeon, Sung Yoon Cho, Dong-Kyu Jin
Annals of Pediatric Endocrinology & Metabolism.2018; 23(4): 229. CrossRef
Rodzinna krzywica hipofosfatemiczna – opis przypadku i przegląd literatury
Agnieszka Jędzura, Omar Bjanid, Piotr Adamczyk, Krzysztof Plesiński, Karolina Klimaszewska-Adamus, Maria Szczepańska
Pediatria Polska.2015; 90(5): 437. CrossRef
Articles in 'Endocrinology and Metabolism' in 2014
Won-Young Lee
Endocrinology and Metabolism.2015; 30(1): 47. CrossRef

A Case of Complete Agenesis of the Dorsal Pancreas in a Patient with Newly Diagnosed Diabetes Mellitus.: Dong Pil Kim, Kang Seo Park, Dong Sun Kim, Bong Suk Ko, Ji Hae Lee, Jae Hyuk Lee, Jong Ho Shin, Byung Jun Kim, Hyun Jin Kim; J Korean Endocr Soc. 2010;25(1):78-83. Published online March 1, 2010; DOI: https://doi.org/10.3803/jkes.2010.25.1.78

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Abstract PDF: Agenesis of the dorsal pancreas is a rare congenital anomaly caused by underdevelopment or agenesis of the dorsal pancreatic bud that forms the upper head, neck, body and tail of the pancreas. We report a case of agenesis of the dorsal pancreas, which was found under examination of diabetes mellitus (DM). A 16-year-old girl was transferred to our hospital because of a positive urine glucose reading during a school-conducted examination. Abdominal computed tomography and magnetic resonance cholangiopancreatography revealed the deficit of the pancreatic body and tail. Diabetes-associated autoimmune antibodies were negative in a blood test. Decreased beta-cell function was demonstrated by oral glucose tolerance and glucagon stimulation tests. Although the notion that agenesis of the dorsal pancreas leads to decreased endocrine or exocrine function is controversial, the results of this study suggest that we should consider these causes of diabetes mellitus. When treating a young patient with diabetes mellitus, we should consider causes of diabetes mellitus such as congenital anomaly or maturity onset diabetes, in addition to type 1 and type 2 diabetes mellitus.

A Case of Graves' Disease with Pancytopenia.: Jong Ho Shin, Hyun Jin Kim, Si Bum Kim, Dong Pil Kim, Bong Suk Ko, Dong Soon Kim, Ji Myung Kim, Soo Jung Gong, Jung Ae Lee; J Korean Endocr Soc. 2009;24(4):272-276. Published online December 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.4.272

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Abstract PDF

Hematological disorders, and especially single lineage abnormalities, have been described in patients suffering with thyrotoxicosis, but pancytopenia is a rare complication of thyrotoxicosis. Pancytopenia with thyrotoxicosis has been reported to be totally reversible with antithyroid drug treatment. We experienced a case with pancytopenia associated with Graves' disease in a 57-year-old woman who had no specific cause of pancytopenia. She presented with dyspnea and palpitation. The laboratory findings revealed thyrotoxicosis and pancytopenia. Increased radioisotope uptake was seen on the thyroid scan and normal cellularity and maturation were found in the bone marrow aspiration biopsy. Based on these findings, she was diagnosed as suffering from Gravesyendisease with pancytopenia. After treatment with propylthiouracil, the blood cell counts were restored to normal as the patient achieved a euthyroid state. We report here on a case of Graves' disease that was complicated by pancytopenia, and all this was normalized after treatment for hyperthyroidism.

Citations

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Non-myeloproliferative Pancytopenia: A Rare Presentation of Thyrotoxicosis
Izzathunnisa Rahmathullah, Maheswaran Umakanth, Suranga Singhapathirane
Cureus.2023;[Epub] CrossRef
Pancytopenia in a surgical patient, a rare presentation of hyperthyroidism
Prabhat Jha, Yogendra Prasad Singh, Bikal Ghimire, Binit Kumar Jha
BMC Surgery.2014;[Epub] CrossRef
A Case of Pancytopenia with Hyperthyroidism
Tae Hoon Kim, Ji Sung Yoon, Byung Sam Park, Dong Won Lee, Jae Ho Cho, Jun Sung Moon, Eui Hyun Kim, Kyu Chang Won, Hyoung Woo Lee
Yeungnam University Journal of Medicine.2013; 30(1): 47. CrossRef

A Case of Neutropenic Enterocolitis Complicating Methimazole-induced Agranulocytosis.: Sang Hyun Park, In Sung Cho, Hyun Jin Kim, Soo Jung Gong, Nae You Kim, Jung Ae Lee; J Korean Endocr Soc. 2007;22(4):282-286. Published online August 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.4.282

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Abstract PDF: Agranulocytosis is a rare complication of antithyroid drug therapy. Neutropenic enterocolitis is characterized by neutropenia plus cecal and ascending colon inflammation, and this is the most feared side effect of agranulocytosis. This is a rare complication of chemotherapy for treating hematological malignancies and less commonly, of the medication used for treating other diseases (e.g., hyperthyroidism). The mortality rate varies from 50 to 100%, with most deaths being due to bowel perforation and sepsis. Therefore, early recognition and proper medical management of neutropenic enterocolitis is important. Recently, early recognition and progress in the management have probably reduced the mortality of this malady, yet there have been no prospective randomized trials or high-quality retrospective studies on the treatment of neutropenic enterocolitis. Therefore, standardized recommendations concerning the indications for surgery cannot be made, but most of these patients are probably not candidates for surgical intervention. Non-surgical management may be a reasonable initial approach for those patients presenting without significant complications such as peritonitis, perforation or bleeding. We report here on a case that was treated with successful medical management for neutropenic enterocolitis that occurred when administering methimazole therapy as an antithyroid drug.

Analysis of Ret Proto-oncogene Mutation in Korean Patients with Medullary Thyroid Carcinomas.: Hyung Hoon Kim, Hyun Jin Kim, Yun Jae Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim, Chang Seok Ki, Jong Won Kim, Jae Hoon Chung; J Korean Endocr Soc. 2003;18(4):360-370. Published online August 1, 2003

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Abstract PDF: BACKGROUND
Medullary thyroid carcinomas (MTC) have been reported as hereditary in about 25 ~30% of cases. The identification of germline mutation in RET proto-oncogene is important in the diagnosis of hereditary MTC, and occurs in three forms: MEN 2A, MEN 2B and familial MTC (FMTC). To evaluate the prevalence of the relationship of RET proto-oncogene mutation and genotype-phenotype was studied in Korean patients with MTC. METHODS: Genomic DNA was obtained from 29 patients, with MTC, who underwent a total thyroidectomy, between 1997 and 2003, at the Samsung Medical Center. There were 7 male and 22 female patients, with an average age of 39, ranging from 20 to 60 years. Exon 10, 11, 13, 14 and 16 of the RET proto-oncogene were amplified, with specific primers, using PCR. A sequencing analysis was performed on the PCR product using an automatic sequencing analyzer. RESULTS: Nine of the 29 patients (31%) were identified as having RET mutations. The average age of these 9 patients was 33 years, ranging from 20 to 51, with a female to male ratio of 2. Five patients had MEN 2A and one had FMTC, with the other 3 thought to have non-hereditary (sporadic) MTC. The 4 patients with MEN 2A had RET mutations on codon 634 of exon 11 (2 patients, C634R; 2 patients, C634Y) and the other patient on codon 618 of exon 10 (C618R). One patient with FMTC had a mutation on codon 634 (C634W). Three patients with sporadic MTC had RET mutations on codon 634 (2 patients, C634Y; 1 patient, C634S). However, no genotype- phenotype relationship could be found, due to the limited number of patients. CONCLUSION: Thirty-one percent (9/29) of the patients with MTC had RET proto-oncogene mutations. Three-quarters (9/12) of the Korean patients with MEN 2A, including another 7 patients reported in 3 papers in Korea, had RET mutations on codon 634 of exon 11 (4 patients, C634R; 4 patients, C634Y; 1 patient, C634W), but a quarter (3/12) had mutations on codon 618 of exon 10 (2 patients, C618R; 1 patient, C618S). Although no relations could be found between the genotypes and phenotypes, extensive prospective studies will be required to verify this.

A Case of Pituitary Tumor Causing Diabetes Insipidus and Associating with Adenoid Cystic Carcinoma in the Bronchus.: Kang Wan Lee, Jong Ryeal Hahm, Mi Yean Kang, Jung Hwa Jung, Gi Dong Lee, Hyun Jin Kim, Sun Il Chung; J Korean Endocr Soc. 2003;18(3):311-317. Published online June 1, 2003

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Abstract PDF: The metastatic tumor occurs in about 6% to 20% of all cases with central diabetes insipidus. Many kinds of cancers such as breast, lung, colon, prostate, leukemia, and lymphoma can metastasize to the pituitary and its stalk. Primary adenoid cystic carcinoma arising in the bronchus is an uncommon disease. It is histologically and ultrastructurally identical to salivary gland adenoid cystic tumor and is regarded as a slowly growing, low graded-malignancy. This is a case report of a 52-year-old woman with diabetes insipidus caused by a pituitary tumor that might have been associated with adenoid cystic carcinoma arising in the bronchus. The patient was diagnosed by water deprivation test, chest CT scan, bronchoscopic biopsy, and brain MRI scan. The water deprivation test showed the patient had central diabetes insipidus, while chest CT scan revealed a lung mass lesion with distal right intermediate bronchial obstruction. The primary malignancy was confirmed by bronchoscopic biopsy. Finally, we confirmed that the patient had a 7mm-sized mass in the posterior pituitary gland and a thickened stalk by brain MRI scan.

A Case of AVP Dependent Bilateral Macronodular Adrenal Hyperplasia.: Hyun Jin Kim, Se Hwa Kim, Yu Mie Rhee, Sung Eun Kim, Chul Woo Ahn, Bong Soo Cha, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh, Sung Kil Lim; J Korean Endocr Soc. 2002;17(4):603-609. Published online August 1, 2002

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Abstract PDF: Adrenocorticotropin (ACTH) independent bilateral macronodular adrenal hyperplasia (AIMAH) is a rare form of Cushing's syndrome, in which unique endocrinological, clinical and histopathological features have been described. In AIMAH, cortisol secretion is autonomous and independent of ACTH, thus plasma ACTH levels are persistently suppressed. Various etiological mechanisms have been proposed to explain the development of AIMAH, the development of aberrant adrenal sensitivity to gastric inhibitory polypeptide (GIP), vasopressin, beta-adrenergic receptor agonists or the presence of circulating adrenal stimulating immunoglobulins have been suggested. We report on a 46-year-old female who had Cushing's syndrome, due to AIMAH, with a positive response to vasopressin.

Peroxiredoxin I and II are Involved in Hydrogen Peroxide Regulation in FRTL-5 Thyroid Cells.: Ho Kim, Tae Hoon Lee, Eun Shin Park, Jae Mi Suh, Soo Jung Park, Hyo Kyun Chung, Hyun Jin Kim, Soo Hong Chae, Do Hee Kim, O Yu Kwon, Young Kun Kim, Min Ho Shong, Heung Kyu Ro; J Korean Endocr Soc. 2000;15(1):55-69. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Peroxiredoxins (Prx) play an important role in regulating cellular differentiation and proliferation in several types of mammalian cells. One mechanism for this action involves modulation of hydrogen peroxide (H2O2)-mediated cellular responses. This report examines the expression of Prx I and Prx II in thyroid cells and their roles in eliminating H2O2 produced in response to TSH. METHODS: The expression of Prx-I and Prx-II were quantiated in FRTL-5 after stimulation with Thyroid stimulating hormone (TSH), Forskolin (FSK), Methimazole (MMI) and hydrogen peroxide (H2O2). Transient transfections were carried out with FRTL-5 cells at 80% confluency and 20microgram of pCRprx I and pCRprx II or equivalent molar amounts of the pCR3.1TM basic vector. Transient transfection used an electroporation technique. Intracellular H2O2 was assayed in FRTL-5 cells with a fluorescent dye, 2', 7'-dichlorofluoresceindiacetate (DCFH-DA). Apoptosis of cells were evaluated by using an detection kit (Promega, Inc., Madison, WI). RESULTS: Prx I and Prx II are constitutively expressed in FRTL-5 thyroid cells. Prx I expression, but not Prx II expression, is stimulated by exposure to TSH and H2O2. In addition, methimazole (MMI) induces a high level of Prx I mRNA and protein in these cells. Overexpression of Prx I and Prx II enhance the elimination of H2O2 produced by TSH in FRTL-5 cells. Treatment with 500microM H2O2 causes apoptosis in FRTL-5 cells as evidenced by standard assays of apoptosis (i.e., terminal deoxynucleotidyl transferase deoxyuridine triphosphate-biotin nick end-labeling (TUNEL), BAX expression and PARP cleavage. Overexpression of Prx I and Prx II reduces the amount of H2O2-induced apoptosis measured by these assays. CONCLUSION: These results suggest that Prx I and Prx II are involved in the removal of H2O2 in thyroid cells, and can protect these cells from undergoing apoptosis. These proteins are likely to be involved in the normal physiological response to TSH-induced production of H2O2 in thyroid cells.

Differential Roles of Transcriptional Coactivators: CBP and CIITA on GAS (Interferon-r Activated Site) - Mediated Transcription in Thyroid Cells.: Eun Shin Park, Ho Kim, Soon Hee You, Soo Jung Park, Hyun Jin Kim, Soo Heung Chae, Do Hee Kim, Hee Jeong Han, O Yu Kwon, Young Kun Kim, Minbo Shong, Heung Kyu Ro; J Korean Endocr Soc. 1999;14(3):493-504. Published online January 1, 2001

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Abstract PDF: BACKGROUND
In the previous studies, we identified that the interferon-gamma activated sequence (GAS) in the 5-flanking region of rat ICAM-1 gene is major element for interferon-y-inducible expression of the gene in rat thyroid cells, FRTL-5. We here, investigated the role of transcriptional coactivators, CBP (CREB binding protein) and CIITA (class II transactivator) in the modulation of the activity of GAS which could interacts with signal transducers and activators of transcription-1 and 3 (STAT1 and STAT3). METHODS: The expression of CBP RNA and protein were quantitated in FRTL-5 after stimulation with interferon-y (IFN-gamma), thyroid stimulating hormone (TSH), forskolin and methimazole. Direct association of CBP with STAT were analyzed by irnmunoprecipitation. The transcriptional roles of CBP and CIITA in the regulation of GAS were assessed by the cotransfection with their expression vectors with reporters; 5-deletion constructs of rat ICAM-1 promoter or 8xGAS-luc constructs, into FRTL-5 thyroid cells. RESULTS: The level of CBP RNA and protein were not changed by the treatment with TSH, IFN-y, forskolin and methimazole in FRTL-5, FRT and BRL liver cells. The CBP could be directly associated with STAT1. Furthernmore, the overexpression of CBP significantly increases the both promoter activities; rat ICAM-1 gene promoter which has GAS element and 8xGAS-luc cassette constructs. However the cotransfection of CI1TA decreased the constitutive and CBP-mediated transactivation of rat ICAM-1 promoter and SxGAS-luc cassette constructs. CONCLUSION: We identified that the two transcriptional coactivators; CBP and CIITA has differential roles in the regulation of transcriptional activity of GAS drived promoter. CBP increases the GAS activity through the direct binding with STATl, but CIITA inhibited the CBP-mediated transactivation of GAS activity.

Serum Leptin Levels in Patients with Thyroid Dysfunction.: Min hO Song, Young Kun Kim, Heung Kyu Ro, Hee Jung Han, Won Chan Joo, Jin Ho Won, Yoon Kim, Hyun Jin Kim, Soo Heung Chae; J Korean Endocr Soc. 1999;14(2):372-378. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Leptin, the product of ob gene, is an important circulating hormone for the regulation of homeostasis of body weight and enegy expenditure. There was a previous reports that thyroid hormone is one of regulating factors of leptin gene expression in vitro. The aim of this study was designed to evaluate the role of thyroid hormone levels in the regulation of circulating leptin concentrations in human. METHODS: A total 16S subjects were studied; 76 patients with Graves disease, 49 patients with Hashimoto disease and 43 control sujjects. The correlation between thryoid hormone and leptin levels were analyzed and serum leptin levels were compared among the groups which was classified by thyroid functional status. Serum leptin concentratios were measured by radioimmunoassay. RESULTS: There were no significant differences in serum leptin levels between the groups of control, Graves disease and Hashimoto disease. The hypothyroid groups of Graves disease which was induced by excessive antithyroid drug treatment showed significant low levels(5.6 +/-2.8 ng/mL) compared to control(9.6 +/- 5.2 ng/ml) and thyrotoxic groups(10.0 +/- 5,0 ng/mL) CONCLUSION: The hypothyroid patients showed low levels of serum leptin concentrations it may indicate that thyroid horrnone play a role in the appropriate secretion of leptin in human.

Serum Soloble Fas in Autoimmune Thyroid Disease.: Min Ho Song, Heung Kyu Ro, Hee Jung Han, Won Chan Joo, Jae Kyu Shin, Hyun Jin Kim, Soo Heung Chae; J Korean Endocr Soc. 1999;14(2):293-300. Published online January 1, 2001

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Abstract PDF: The Changes of soluble Fas levels in Patients with Autoimmune Thyroid Diseases BACKGROUD: Apoptosis was observed in thyroid tissue from Hashimoto disease but not those from Graves disease. Recently Fas and Fas ligand interactions among thyrocytes were suggested to development of clinical hypothyroidism in Hashimoto disease.Soluble Fas produced as the form lacking the tranmembrane domain due to alternative splicing, is supposed to inhibit Fas-Fas ligand interaction and blocks Fas mediated apoptosis. METHODS: In tbis study, we measured serum soluble Fas to determine the possible involvement of this molecule in the autoimmune thyroid disease by enzyme linked immunosorbant assay in 29 patients with Graves disease, 30 patients with Hashimotos disease and 19 normal controls. RESULTS: Compared with normal subjeets (4.26 +/- 1.00 U/mL), soluble Fas was not increased in patients with Graves disease (4.23 +/- 1.14 U/mL, p>0.05) but it was increased in throtoxic Graves patients (4.70 +/- 1.26 U/mL, p<0.05) compared to euthyroid Graves (3.72 +/- 0.73 U/mL, p<0.05) and normal subjects (4.26 +/- 1.00 U/mL, p<0.05). The euthyroid and hypothyroid patients with Hashimoto disease showed low soluble Fas levels, 2.94 +/- 0.54 U/mL and 2.74 U/mL, respectively compare to the patients with Graves disease and normal subjects. The thyroid hormone levels to (T3 T4 and free T4) showed positive correlation with the serum titers of antithyroid autoantibodies, antithyroglobuin antibodies, antiperoxidase antibodies and thyrotropin binding inhibitor immunoglobulins. CONCLUSION: We found that the patients with thyrotoxic Graves disease had increased level of serum soluble Fas and the patients with Hashimoto disease showed low levels of soluble Fas compared to normal controls. Increased soluble Fas in Graves disease suggests increased expression of alternatively spliced Fas mRNA variant and decreased soluble Fas in Hashimoto disease suggests decreased Fas mRNA variant and increased full length membrane Fas, so these findings are related to the promotion of apoptosis of thyroid cells during autoimmune reaction in Hashimotos disease.

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