Endocrinology and Metabolism

Original Articles

Thyroid
Clinical Outcomes of Repeated Radioactive Iodine Therapy for Graves’ Disease: Min Joo Kim, Sun Wook Cho, Ye An Kim, Hoon Sung Choi, Young Joo Park, Do Joon Park, Bo Youn Cho; Endocrinol Metab. 2022;37(3):524-532. Published online June 16, 2022; DOI: https://doi.org/10.3803/EnM.2022.1418

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Background
Radioactive iodine (RAI) therapy is a successful therapeutic modality for Graves’ disease. However, RAI therapy can fail, and RAI therapy after antithyroid drugs (ATDs) has a lower remission rate. Therefore, many patients require repeated RAI therapy. This study investigated the clinical outcomes of repeated RAI therapy for Graves’ disease.
Methods
Patients who underwent RAI therapy as second-line therapy after failure of ATD treatment between 2001 and 2015 were reviewed. Remission was defined as hypothyroid or euthyroid status without ATD, and with or without levothyroxine at 12 months after RAI therapy.
Results
The 1-year remission rate after 2nd RAI therapy (66%, 152/230) is significantly higher than that after 1st RAI therapy (48%, 393/815) or long-term ATD treatment after 1st RAI therapy failure (42%). The clinical response to 2nd RAI therapy was more rapid. The median time intervals from the 2nd RAI therapy to ATD discontinuation (1.3 months) and to the start of levothyroxine replacement (2.5 months) were significantly shorter than those for the 1st RAI therapy. A smaller goiter size, a longer time interval between the 1st and 2nd RAI therapies, and a longer ATD discontinuation period predicted remission after the 2nd RAI therapy. Finally, in 78 patients who failed the 2nd RAI therapy, the mean ATD dosage significantly reduced 5.1 mg over 12 months.
Conclusion
Repeated RAI therapy can be a good therapeutic option, especially in patients with smaller goiters and those who are more responsive to the 1st RAI therapy.

Citations

Citations to this article as recorded by

The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves’ Disease
Jin Yu, Han-Sang Baek, Chaiho Jeong, Kwanhoon Jo, Jeongmin Lee, Jeonghoon Ha, Min Hee Kim, Jungmin Lee, Dong-Jun Lim
Endocrinology and Metabolism.2023; 38(3): 338. CrossRef
Effect of liver dysfunction on outcome of radioactive iodine therapy for Graves’ disease
Yuyang Ze, Fei Shao, Xuefeng Feng, Shanmei Shen, Yan Bi, Dalong Zhu, Xiaowen Zhang
BMC Endocrine Disorders.2022;[Epub] CrossRef

Calcium & Bone Metabolism
Unveiling Genetic Variants Underlying Vitamin D Deficiency in Multiple Korean Cohorts by a Genome-Wide Association Study: Ye An Kim, Ji Won Yoon, Young Lee, Hyuk Jin Choi, Jae Won Yun, Eunsin Bae, Seung-Hyun Kwon, So Eun Ahn, Ah-Ra Do, Heejin Jin, Sungho Won, Do Joon Park, Chan Soo Shin, Je Hyun Seo; Endocrinol Metab. 2021;36(6):1189-1200. Published online December 2, 2021; DOI: https://doi.org/10.3803/EnM.2021.1241

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Background
Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS).
Methods
We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed.
Results
rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles.
Conclusion
The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

Citations

Citations to this article as recorded by

Vitamin D-associated genetic variants in the Brazilian population: Investigating potential instruments for Mendelian randomization
Caroline De Souza Silverio , Carolina Bonilla
Biomédica.2024; 44(1): 45. CrossRef
Implications of vitamin D deficiency in systemic inflammation and cardiovascular health
Sanjay Kumar Dey, Shashank Kumar, Diksha Rani, Shashank Kumar Maurya, Pratibha Banerjee, Madhur Verma, Sabyasachi Senapati
Critical Reviews in Food Science and Nutrition.2023; : 1. CrossRef
Association between Vitamin D Deficiency and Clinical Parameters in Men and Women Aged 50 Years or Older: A Cross-Sectional Cohort Study
Ji Hyun Lee, Ye An Kim, Young Sik Kim, Young Lee, Je Hyun Seo
Nutrients.2023; 15(13): 3043. CrossRef
Single nucleotide polymorphisms in vitamin D binding protein and 25-hydroxylase genes affect vitamin D levels in adolescents of Arab ethnicity in Kuwait
Abdur Rahman, Mohamed Abu-Farha, Arshad Channanath, Maha M. Hammad, Emil Anoop, Betty Chandy, Motasem Melhem, Fahd Al-Mulla, Thangavel Alphonse Thanaraj, Jehad Abubaker
Frontiers in Endocrinology.2023;[Epub] CrossRef
Recent Information on Vitamin D Deficiency in an Adult Korean Population Visiting Local Clinics and Hospitals
Rihwa Choi, Sung-Eun Cho, Sang Gon Lee, Eun Hee Lee
Nutrients.2022; 14(9): 1978. CrossRef
The Multiple Effects of Vitamin D against Chronic Diseases: From Reduction of Lipid Peroxidation to Updated Evidence from Clinical Studies
Massimiliano Berretta, Vincenzo Quagliariello, Alessia Bignucolo, Sergio Facchini, Nicola Maurea, Raffaele Di Francia, Francesco Fiorica, Saman Sharifi, Silvia Bressan, Sara N. Richter, Valentina Camozzi, Luca Rinaldi, Carla Scaroni, Monica Montopoli
Antioxidants.2022; 11(6): 1090. CrossRef
A Genome-Wide Association Study of Genetic Variants of Apolipoprotein A1 Levels and Their Association with Vitamin D in Korean Cohorts
Young Lee, Ji Won Yoon, Ye An Kim, Hyuk Jin Choi, Byung Woo Yoon, Je Hyun Seo
Genes.2022; 13(9): 1553. CrossRef
Genetic Determinants of 25-Hydroxyvitamin D Concentrations and Their Relevance to Public Health
Elina Hyppönen, Karani S. Vimaleswaran, Ang Zhou
Nutrients.2022; 14(20): 4408. CrossRef
On the Centennial of Vitamin D—Vitamin D, Inflammation, and Autoimmune Thyroiditis: A Web of Links and Implications
Leonidas H. Duntas, Krystallenia I. Alexandraki
Nutrients.2022; 14(23): 5032. CrossRef
The genetic and epigenetic contributions to the development of nutritional rickets
Innocent Ogunmwonyi, Adewale Adebajo, Jeremy Mark Wilkinson
Frontiers in Endocrinology.2022;[Epub] CrossRef

Thyroid
Star-Shaped Intense Uptake of ¹³¹I on Whole Body Scans Can Reflect Good Therapeutic Effects of Low-Dose Radioactive Iodine Treatment of 1.1 GBq: Sung Hye Kong, Jung Ah Lim, Young Shin Song, Shinje Moon, Ye An Kim, Min Joo Kim, Sun Wook Cho, Jae Hoon Moon, Ka Hee Yi, Do Joon Park, Bo Youn Cho, Young Joo Park; Endocrinol Metab. 2018;33(2):228-235. Published online May 4, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.228

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Background

After initial radioactive iodine (RAI) treatment in differentiated thyroid cancer patients, we sometimes observe a star-shaped region of intense uptake of ¹³¹I on whole body scans (WBSs), called a ‘star artifact.’ We evaluated the clinical implications of star artifacts on the success rate of remnant ablation and long-term prognosis.

Methods

Total 636 patients who received ¹³¹I dose of 1.1 GBq for the initial RAI therapy and who did not show distant metastasis at the time of diagnosis were retrospectively evaluated. A negative second WBS was used for evaluating the ablation efficacy of the RAI therapy. Among them, 235 patients (36.9%) showed a star artifact on their first WBS.

Results

In patients with first stimulated thyroglobulin (sTg) levels ≤2 ng/mL, patients with star artifacts had a higher rate of negative second WBS compared with those without star artifacts (77.8% vs. 63.9%, P=0.044), and showed significantly higher recurrence-free survival (P=0.043) during the median 8.0 years (range, 1.0 to 10.0) of follow-up. The 5- and 10-year recurrence rates (5YRR, 10YRR) were also significantly lower in patients with star artifacts compared with those without (0% vs. 4.9%, respectively, P=0.006 for 5YRR; 0% vs. 6.4%, respectively, P=0.005 for 10YRR). However, ablation success rate or recurrence-free survival was not different among patients whose first sTg levels >2 ng/mL regardless of star artifacts.

Conclusion

Therefore, star artifacts at initial RAI therapy imply a good ablation efficacy or a favorable long-term prognosis in patients with sTg levels ≤2 ng/mL.

Citations

Citations to this article as recorded by

Prognostic value of star-shaped intense uptake of 131I in thyroid cancer patients
Liu Xiao, Wen Jie Zhang, Yue Qi Wang, Lin Li
Revista Española de Medicina Nuclear e Imagen Molecular (English Edition).2021; 40(1): 30. CrossRef
Valores pronósticos de la captación en estrella de 131I en pacientes con cáncer diferenciado de tiroides
L. Xiao, W.J. Zhang, Y.Q. Wang, L. Li
Revista Española de Medicina Nuclear e Imagen Molecular.2021; 40(1): 30. CrossRef
Comparison between planar and single-photon computed tomography images for radiation intensity quantification in iodine-131 scintigraphy
Yusuke Iizuka, Tomohiro Katagiri, Minoru Inoue, Kiyonao Nakamura, Takashi Mizowaki
Scientific Reports.2021;[Epub] CrossRef

Endocrine Research
Thyroid Hormone Regulates the mRNA Expression of Small Heterodimer Partner through Liver Receptor Homolog-1: Hwa Young Ahn, Hwan Hee Kim, Ye An Kim, Min Kim, Jung Hun Ohn, Sung Soo Chung, Yoon-Kwang Lee, Do Joon Park, Kyong Soo Park, David D. Moore, Young Joo Park; Endocrinol Metab. 2015;30(4):584-592. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.584

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Background

Expression of hepatic cholesterol 7α-hydroxylase (CYP7A1) is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP). In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1).

Methods

We injected thyroid hormone (triiodothyronine, T3) to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR). Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA) were also performed using human hepatoma cell line

Results

Initial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor β/retinoid X receptor α/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding.

Conclusion

We found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.

Citations

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Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms
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Review Article

Thyroid
Prevalence and Risk Factors of Subclinical Thyroid Disease: Ye An Kim, Young Joo Park; Endocrinol Metab. 2014;29(1):20-29. Published online March 14, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.1.20

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Subclinical thyroid disease is defined biochemically by an abnormal thyrotropin (TSH) level and normal serum-free thyroxine level. The prevalence of this condition varies according to the reference range for TSH and geographic or demographic factors. Recently, several studies, including our community-based cohort studies, have reported on the incidence of subclinical thyroid disease in Korea. Using these studies, we reviewed the prevalence and risk factors of subclinical thyroid disease, focusing on subclinical hypothyroidism.

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Case Reports

Adrenal gland
Adrenocorticotropic Hormone-Independent Cushing Syndrome with Bilateral Cortisol-Secreting Adenomas: Eu Jeong Ku, A Ram Hong, Ye An Kim, Jae Hyun Bae, Mee Soo Chang, Sang Wan Kim; Endocrinol Metab. 2013;28(2):133-137. Published online June 18, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.2.133

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A 48-year-old woman was incidentally found to have bilateral adrenal masses, 2.8 cm in diameter on the right, and 2.3 cm and 1.7 cm in diameter on the left, by abdominal computed tomography. The patient had a medical history of hypertension, which was not being controlled by carvedilol, at a dose of 25 mg daily. She presented with signs and symptoms that suggested Cushing Syndrome. We diagnosed adrenocorticotropic hormone (ACTH)-independent Cushing Syndrome based on the results of basal and dynamic hormone tests. Adrenal vein sampling (AVS) was performed to localize a functioning adrenal cortical mass. AVS results were consistent with hypersecretion of cortisol from both adrenal glands, with a cortisol lateralization ratio of 1.1. Upon bilateral laparoscopic adrenalectomy, bilateral ACTH-independent adrenal adenomas were found. The patient's signs and symptoms of Cushing Syndrome improved after surgery just as the blood pressure was normalized. After surgery, the patient was started on glucocorticoid and mineralocorticoid replacement therapy.

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Concomitant coexistence of ACTH‐dependent and independent Cushing syndrome
Ach Taieb, Saad Ghada, Gorchène Asma, Ben Abdelkrim Asma, Kacem Maha, Ach Koussay
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The Value of Adrenal Androgens for Correcting Cortisol Lateralization in Adrenal Venous Sampling in Patients with Normal Cortisol Secretion
Wenjing Zhang, Keying Zhu, Hongyun Li, Yan Zhang, Dalong Zhu, Xuebin Zhang, Ping Li
International Journal of Endocrinology.2019; 2019: 1. CrossRef
Adrenal venous sampling in patients with ACTH-independent hypercortisolism
Eleni Papakokkinou, Hugo Jakobsson, Augustinas Sakinis, Andreas Muth, Bo Wängberg, Olof Ehn, Gudmundur Johannsson, Oskar Ragnarsson
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ACTH-independent Cushing’s syndrome with bilateral cortisol-secreting adrenal adenomas: a case report and review of literatures
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Thyroid
Two Cases of Methimazole-Induced Insulin Autoimmune Syndrome in Graves' Disease: Eun Roh, Ye An Kim, Eu Jeong Ku, Jae Hyun Bae, Hye Mi Kim, Young Min Cho, Young Joo Park, Kyong Soo Park, Seong Yeon Kim, Soo Heon Kwak; Endocrinol Metab. 2013;28(1):55-60. Published online March 25, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.1.55

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We report here the cases of two females with Graves' disease who developed insulin autoimmune syndrome after treatment with methimazole. The patients exhibited a sudden altered mental state after treatment with methimazole for approximately 4 weeks. Patients had hypoglycemia with serum glucose below 70 mg/dL, and laboratory findings showed both high levels of serum insulin and high titers of insulin autoantibodies. The two women had never been exposed to insulin or oral antidiabetic agents, and there was no evidence of insulinoma in imaging studies. After glucose loading, serum glucose, and total insulin levels increased abnormally. One of the patient was found to have HLA-DRB1*0406, which is known to be strongly associated with methimazole-induced insulin autoimmune syndrome. After discontinuation of methimazole, hypoglycemic events disappeared within 1 month. Insulin autoantibody titer and insulin levels decreased within 5 months and there was no further development of hypoglycemic events. We present these cases with a review of the relevant literature.

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Original Article

Characterization of Incidentally Detected Adrenal Pheochromocytoma.: Ye An Kim, Yul Hwangbo, Min Joo Kim, Hyung Jin Choi, Je Hyun Seo, Yenna Lee, Soo Heun Kwak, Eu Jeong Ku, Tae Jung Oh, Eun Roh, Jae Hyun Bae, Jung Hee Kim, Kyoung Soo Park, Seong Yeon Kim; Endocrinol Metab. 2012;27(2):132-137. Published online June 20, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.2.132

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BACKGROUND
In approach to an adrenal incidentaloma, early exclusion of pheochromocytoma is clinically important, due to the risk of catecholamine crisis. The aims of this study are to investigate the characteristics of incidentally detected pheochromocytomas, compared with that of the other adrenal incidentalomas, and to compare these characteristics with those of symptomatic pheochromocytomas. METHODS: In this retrospective study, we reviewed the medical records of 198 patients with adrenal incidentaloma from 2001 to 2010. We analyzed the clinical, laboratory and radiological data of pheochromocytomas, in comparison with those of the other adrenal incidentalomas. We also compared the characteristics of these incidentally detected pheochromocytomas with the medical records of 28 pathologically proven pheochromocytomas, diagnosed based on typical symptoms. RESULTS: Among the 198 patients with adrenal incidentaloma, nineteen patients were diagnosed with pheochromocytoma. Pheochromocytomas showed larger size and higher Hounsfield unit at precontrast computed tomography (CT) than did non-pheochromocytomas. All pheochromocytomas were larger than 2.0 cm, and the Hounsfield units were 19 or higher in precontrast CT. When both criteria of size > 2.0 cm and Hounsfield unit > 19 were met, the sensitivity and specificity for the diagnosis of pheochromocytoma were 100% and 79.3%, respectively. Compared with patients with pheochromocytoma, diagnosed based on typical symptoms, patients with incidentally detected pheochromocytoma were older, presented less often with hypertension, and showed lower levels of 24-hour urine metanephrine. CONCLUSION: Adrenal incidentaloma with < 2.0 cm in size or < or = 19 Hounsfield units in precontrast CT imaging was less likely to be a pheochromocytoma. Patients with incidentally discovered pheochromocytoma showed lower catecholamine metabolites, compared with those patients with symptomatic pheochromocytoma.

Citations

Citations to this article as recorded by

Guidelines for the Management of Adrenal Incidentaloma: the Korean Endocrine Society, Committee of Clinical Practice Guidelines
Jung-Min Lee, Mee Kyoung Kim, Seung-Hyun Ko, Jung-Min Koh, Bo-Yeon Kim, Sang-Wan Kim, Soo-Kyung Kim, Hae-Jin Kim, Ohk-Hyun Ryu, Juri Park, Jung-Soo Lim, Seong Yeon Kim, Young Kee Shong, Soon Jib Yoo
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Clinical Guidelines for the Management of Adrenal Incidentaloma
Jung-Min Lee, Mee Kyoung Kim, Seung-Hyun Ko, Jung-Min Koh, Bo-Yeon Kim, Sang Wan Kim, Soo-Kyung Kim, Hae Jin Kim, Ohk-Hyun Ryu, Juri Park, Jung Soo Lim, Seong Yeon Kim, Young Kee Shong, Soon Jib Yoo
Endocrinology and Metabolism.2017; 32(2): 200. CrossRef
Characterization of Incidentally Detected Adrenal Pheochromocytoma
Soon Jib Yoo, Woohyeon Kim
Endocrinology and Metabolism.2012; 27(2): 116. CrossRef

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