Endocrinology and Metabolism

Original Articles

Clinical Study
A Phase II Multi-Center, Non-Randomized, Parallel Group, Non-Inferiority Study to Compare the Efficacy of No Radioactive Iodine Remnant Ablation to Remnant Ablation Treatment in Low- to Intermediate-Risk of Papillary Thyroid Cancer: The MOREthyroid Trial Protocol: Eun Kyung Lee, You Jin Lee, Young Joo Park, Jae Hoon Moon, Ka Hee Yi, Koon Soon Kim, Joo Hee Lee, Sun Wook Cho, Jungnam Joo, Yul Hwangbo, Sujeong Go, Do Joon Park; Endocrinol Metab. 2020;35(3):571-577. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.681

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Background
Radioactive iodine (RAI) remnant ablation is recommended in patients with papillary thyroid cancer (PTC) and extrathyroidal extension or central lymph node metastasis. However, there exists little evidence about the necessity of remnant ablation in PTC patients with low- to intermediate-risk, those have been increasing in recent decades.
Methods
This multicenter, prospective, non-randomized, parallel group clinical trial will enroll 310 eligible patients with low- to intermediate-risk of thyroid cancer. Inclusion criteria are patients who recently underwent total thyroidectomy for PTC with 3 or less tumors of size 1≤ to ≤2 cm with no microscopic extension and N0/x, or size ≤2 cm with microscopic extension and/or N1a (number of lymph node ≤3, size of tumor foci ≤0.2 cm, and lymph node ratio <0.4). Patients choose to undergo RAI ablation (¹³¹I, dose 1.1 GBq) or diagnostic whole-body scan (DxWBS) (¹³¹I or ¹²³I, dose 0.074 to 0.222 GBq), followed by subsequent measurement of stimulated thyroglobulin (sTg) within 1 year. Survey for quality of life (QOL) will be performed at baseline and at 1 year after follow-up. The total enrollment period is 5 years, and patients will be followed up for 1 year. The primary endpoint is the non-inferiority of surgery alone to surgery with ablation in terms of biochemical remission (BCR) rate (sTg ≤2 ng/mL) without evidence of structural recurrence. The secondary endpoint was the difference of QOL.
Conclusion
This study will evaluate whether surgery alone achieves similar BCR and improved QOL compared to RAI ablation in patients with low- to intermediate-risk PTC within 1 year.

Citations

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Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part I. Initial Management of Differentiated Thyroid Cancers - Chapter 6. Radioactive Iodine Treatment after Thyroidectomy 2024
Sohyun Park, Ari Chong, Ho-Cheol Kang, Keunyoung Kim, Sun Wook Kim, Dong Gyu Na, Young Joo Park, Ji-In Bang, Youngduk Seo, Young Shin Song, So Won Oh, Eun Kyung Lee, Dong-Jun Lim, Yun Jae Chung, Chae Moon Hong, Sang-Woo Lee
International Journal of Thyroidology.2024; 17(1): 97. CrossRef
Radioactive Iodine Therapy in Differentiated Thyroid Cancer: Summary of the Korean Thyroid Association Guidelines 2024 from Nuclear Medicine Perspective, Part-II
So Won Oh, Sohyun Park, Ari Chong, Keunyoung Kim, Ji-In Bang, Youngduk Seo, Chae Moon Hong, Sang-Woo Lee
Nuclear Medicine and Molecular Imaging.2024;[Epub] 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.

Citations

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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.

Citations

Citations to this article as recorded by

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

Case Reports

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

Citations to this article as recorded by

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 Gastrointestinal Stromal Tumor with Recurrent Hypoglycemia.: Sun Hee Ko, Seok Hwan Kim, Il Ho Maeng, Koon Soon Kim, Yi Sun Jang, Hye Soo Kim, Jong Min Lee, Suk Young Park, Sang Bum Kang; Endocrinol Metab. 2010;25(2):125-130. Published online June 1, 2010; DOI: https://doi.org/10.3803/EnM.2010.25.2.125

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Abstract PDF: Non-islet cell tumor induced hypoglycemia (NICTH) is attributable to overproduction of insulin-like growth factor-II (IGF-II) by solid tumors, and these tumors usually originate from mesenchymal or epithelial cells. Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor and most commonly find in the gastrointestinal tract. It is usually expresses the CD117 (stem cell factor receptor, c-kit) detected by immunohistochemistry. Hypoglycemia associated with GIST is very rare and this has not yet been reported in Korea. A 72-year-old man was hospitalized due to frequent episodes of confusion. It was observed that non-hyperinsulinemic hypoglycemia, an elevated serum IGF-II level and a huge liver mass. The histology of liver mass showed c-kit (CD117) positivity, which was consistent with GIST, but it was surgically unresectable. He was treated with imatinib mesylate. Although he recieved palliative treatment, he still experienced intermittent fasting hypoglycemia. After 2 months, the serum IGF-II level was even higher than before. We changed imatinib mesylate to sunitinib malate and performed radiotherapy on the liver mass. Although the change of the liver mass was not significant, he did not suffer from hypoglycemia for three months afterwards.

Original Article

Comparing the Prevalence of Primary Aldosteronism in Hypertensive Diabetic and Non-diabetic Patients.: Yi Sun Jang, Koon Soon Kim, Hye Soo Kim; J Korean Endocr Soc. 2009;24(4):254-259. Published online December 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.4.254

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Abstract PDF: BACKGROUND
Primary aldosteronism is the most common cause of secondary hypertension in humans. Its prevalence is estimated to be 10-15% among hypertensive patients. It is also associated with insulin resistance and diabetes mellitus. The aim of our study was to compare the prevalence of primary aldosteronism in hypertensive patients with presence of diabetes mellitus. METHODS: We reviewed retrospectively the clinical records of 104 hypertensive patients for whom we also measured plasma renin activity (PRA) and plasma aldosterone concentrations (PAC). RESULTS: Among 104 hypertensive patients, 44 had diabetes and 60 did not. There were no significant differences in clinical characteristics between non-diabetic and diabetic patients except for age and the number of antihypertensive agents. Patients with target organ damage were more common among diabetic patients. There was no correlation between PAC and the number of target organs damaged. In addition, Four patients from the non-diabetic and two from the diabetic group had a ratio over 30 for PRA/PAC and a PAC of over 15 ng/dL. Two non-diabetic patients and one diabetic patient were found, on abdomen CT, to have an adrenal adenoma. The rest of the patients refused further tests. CONCLUSION: The prevalence of primary aldosteronism in diabetic patients does not differ significantly from that in non-diabetic patients. Therefore, the present routine screening test for primary aldosteronism in hypertensive diabetic patients is not recommended.

Case Report

Two Cases of Simple Virilizing Congenital Adrenal Hyperplasia with Compound Heterozygous Mutations of CYP21 Gene.: Koon Soon Kim, Yun Sun Choi, Youn Sun Bai, So Young Rha, Young Suk Jo, Minho Shong; J Korean Endocr Soc. 2007;22(4):299-304. Published online August 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.4.299

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Abstract PDF: Steroid 21-hydroxylase deficiency is the most frequent cause of congenital adrenal hyperplasia (CAH), which is an inherited inability to synthesize cortisol. Actually, CAH is caused by mutations in the CYP21 gene encoding the steroid 21-hydroxylase enzyme. In some cases, discordance has been observed between the genotype and the phenotype. We recently experienced two cases of simple virilizing congenital adrenal hyperplasia with compound heterozygous mutations of the CYP21 gene. The patients had primary amenorrhea and showed virilization. We have described these two cases along with a review of the literature.

Original Articles

The Relationship between the BRAF Mutations in Thyroid Papillary Carcinomas and the Prognostic Factors.: So Young Rha, Jun Chul Lee, Ki Hyun Kwon, Hyo Jin Lee, Koon Soon Kim, Young Suk Jo, Bon Jeong Ku, Minho Shong, Young Kun Kim, Heung Kyu Ro; J Korean Endocr Soc. 2005;20(3):224-229. Published online June 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.3.224

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Abstract PDF

BACKGROUND
Thyroid cancers account for about 1% of all human malignancies, with papillary thyroid carcinomas being the most common istotype. Several investigators have recently identified the most common BRAF mutation, the T1796A transversion mutation, in 29~69% of papillary thyroid cancers. The BRAF mutation has been demonstrated as a novel prognostic biomarker for the prediction of poor clinicopathological outcomes, such as increased incidence of extrathyroid invasion and distant metastasis of the tumor. In this study, we investigated the prevalence of the BRAF mutation of thyroid tissues obtained by a thyroidectomy, and its correlation with the clinicopathological outcomes. METHODS: We studied 36 thyroid tissues obtained from 24 women and 12 men by thyroidectomies, including 30 papillary carcinomas, 3 follicular carcinomas, 1 medullary carcinoma and 2 nodular hyperplasia. The mutation was sought in all specimens using DNA sequencing. RESULTS: We studied the BRAF exon 15 T1796A in these 36 thyroid tissues. The mean age at surgery was 46.6, ranging from 18 to 72 years, with a median tumor size of 2.79, ranging from 1.5 to 4.5cm. At the time of diagnosis, 27 of the 34 patients presented with some kind of extrathyroidal invasion of the tumor, and 16 had lymph node metastases. 16, 2 and 16 patients were in stages I, II and III, respectively. There was no distant metastasis. A missense mutation was found at T1796A in exon 15 in 21 of the 30 papillary carcinomas(70%). The other thyroid diseases, including the 3 follicular carcinomas, 1 medullary carcinoma and 2 nodular hyperplasia show no exon 15 T1759A transversion mutation. No statistically significant association was found between the BRAF mutations and clinicopathological characteristics of papillary carcinomas. CONCLUSION: The BRAF mutation is a important genetic alteration, with a high prevalence in papillary thyroid carcinomas. However, there was no significant association between the BRAF mutation and any of the clinicopathological factors. Further, large scale studies will be needed to evaluate the correlation between the BRAF mutation and the clinicopathological factors

Citations

Citations to this article as recorded by

Detection of Plasma BRAFV600EMutation Is Associated with Lung Metastasis in Papillary Thyroid Carcinomas
Bo Hyun Kim, In Joo Kim, Byung Joo Lee, Jin Choon Lee, In Suk Kim, Seong-Jang Kim, Won Jin Kim, Yun Kyung Jeon, Sang Soo Kim, Yong Ki Kim
Yonsei Medical Journal.2015; 56(3): 634. CrossRef
Diagnostic Effectiveness of PCR-based Tests DetectingBRAFMutation for Treating Malignant Melanoma: A Systematic Review
Hae-Won Shin, Ryeo-Jin Ko, Min Lee, Hee-Young Bang, Kye-Chul Kwon, Jong-Woo Park, Sun-Hoe Koo
Laboratory Medicine Online.2014; 4(4): 203. CrossRef
BRAFV600E mutation does not serve as a prognostic factor in Korean patients with papillary thyroid carcinoma
Dongbin Ahn, June Sik Park, Jin Ho Sohn, Jae Hyug Kim, Sun-Kyun Park, An Na Seo, Ji Young Park
Auris Nasus Larynx.2012; 39(2): 198. CrossRef
The Frequency ofBRAFMutation in Very Small Papillary Thyroid Carcinomas
Taeeun Kim, Ji-Hyun Roh, Hee-Jung Park, Jee Eun Kwon, So-Young Kang, Yoon-La Choi, Young Lyun Oh
The Korean Journal of Pathology.2010; 44(3): 308. CrossRef
ras Mutation in Korean Papillary Thyroid Carcinomas
Jung Hwa Jung, Keun-Sook Kim, Tae Sik Jung, Young Lyun Oh, Hye Won Jang, Hye Seung Jung, Yong-Ki Min, Myung-Shik Lee, Moon-Kyu Lee, Kwang-Won Kim, Jae Hoon Chung
Journal of Korean Endocrine Society.2007; 22(3): 203. CrossRef

The Adequacy of Ultrasound-Guided Fine Needle Aspiration in Thyroid Nodules.: Hyo Jin Lee, So Young Rha, Ki Hyun Kwon, Jun Chul Lee, Koon Soon Kim, Young Suk Jo, Bon Jeong Ku, Minho Shong, Young Kun Kim, Heung Kyu Ro; J Korean Endocr Soc. 2005;20(2):154-159. Published online April 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.2.154

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Abstract PDF

BACKGROUND
Fine needle aspiration(FNA) is an accurate and safe method for the diagnosis of thyroid nodules. One of the limitations of FNA is the variable rate of unsatisfactory specimens, especially in small sized, deep seated or complex cystic nodules. To overcome this problem, ultrasound-guided FNA(US-FNA) has been widely used. In this study, the adequacy of cytologic specimens by US-FNA was compared with that of conventional palpation-guided FNA(P-FNA). METHODS: The medical records of all patients who were engaged in FNA due to thyroid nodules at Chungnam National University Hospital from January 2003 to July 2004 were retrospectively examined. The US-FNA and P-FNA were performed in 114 and 185 patients, respectively. RESULTS: Comparison of the adequacy of the two techniques in providing sufficient material for the cytologic diagnosis showed that specimens in 24(13.0%) and 6(5.3%) patients collected by P-FNA and US-FNA, respectively, were unsatisfactory(P=0.031). A total of 23 patients underwent thyroid surgery due to strong suspicion of malignancy at cytologic finding and/or on clinical judgement. Seventeen patients belonged to the P-FNA group and 6 patients to the US-FNA group. In the P-FNA group, a histologic diagnosis revealed two false-negative cytologic findings, but no false-negative findings were found in the US-FNA group. CONCLUSION: Compared with P-FNA, US-FNA may reduce the possibility of unsatisfactory cytologic specimens and the rate of false-negative diagnosis, and may improve the diagnostic accuracy in investigating thyroid nodules

Citations

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Prevalence of Thyroid Nodules Detected by Ultrasonography in Adults for Health Check-up and Analysis of Fine Needle Aspiration Cytology
Jae Hoon Chung
Journal of Korean Endocrine Society.2008; 23(6): 391. CrossRef

The STAT3 in Glucose Homeostasis.: Bon Jeong Ku, Su Hyeon Park, Koon Soon Kim, Young Kun Lim, Min Ho Shong; J Korean Endocr Soc. 2004;19(3):274-280. Published online June 1, 2004

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