Endocrinology and Metabolism

Review Article

Calcium & Bone Metabolism
Review and Update of the Risk Factors and Prevention of Antiresorptive-Related Osteonecrosis of the Jaw: Ha Young Kim; Endocrinol Metab. 2021;36(5):917-927. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1170

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Antiresorptive-related osteonecrosis of the jaw (ARONJ) is a rare but serious adverse event of bisphosphonate or denosumab administration; it is associated with severe pain and a deteriorated quality of life. Since its first report in 2003, there have been many studies on its definition, epidemiology, pathophysiology, diagnosis, and treatment. Nevertheless, the epidemiology and mechanisms underlying this condition have not yet been fully delineated and several risk factors are known. Moreover, as there is no effective treatment currently available for osteonecrosis of the jaw, prevention is essential. Furthermore, close cooperation between prescribing physicians and dentists is important. The aim of this review was to provide up-to-date information regarding the risk factors and prevention of ARONJ from a physician’s perspective.

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Risk factors for dental findings of the development of medication-related osteonecrosis of the jaw: Investigation of 3734 teeth in cancer patients receiving high dose antiresorptive agents
Mitsunobu Otsuru, Yoshinari Fujiki, Sakiko Soutome, Norio Nakamura, Taro Miyoshi, Tomofumi Naruse, Mizuho Ohnuma, Yuka Hotokezaka, Satoshi Rokutanda, Masahiro Umeda
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Editorial: Immunological processes in maxillofacial bone pathology
Matthias Tröltzsch
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Polysacharide of Agaricus blazei gel mitigates bone necrosis in model of the jaws related to bisphosphonate via Wnt signaling
Vanessa Costa de Sousa, Fátima Regina Nunes Sousa, Raquel Felipe Vasconcelos, Gisele Angelino Barreto, Conceição S. Martins, Nilson Romero Dias, Sislana Costa, Maria Jennifer Chaves Bernardino, George de Almeida Silva, Nadine Linhares, Delane Gondim, Mirn
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Prevention of medication-related osteonecrosis of the jaw after tooth extraction by local administration of antibiotics and atelocollagen sponge: A preliminary study
Natsumi Nakamura, Sakiko Soutome, Akira Imakiire, Satoshi Rokutanda, Seigo Ohba, Shunsuke Sawada, Yuka Kojima, Yuki Sakamoto, Yoshiko Yamamura, Madoka Funahara, Mitsunobu Otsuru, Masahiro Umeda
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When and how to stop denosumab therapy in a patient with osteoporosis
Eirena L. Goulden, Rachel K. Crowley
Clinical Endocrinology.2023; 98(5): 649. CrossRef
Clinical and Histopathological Aspects of MRONJ in Cancer Patients
George Adrian Ciobanu, Laurențiu Mogoantă, Adrian Camen, Mihaela Ionescu, Daniel Vlad, Ionela Elisabeta Staicu, Cristina Maria Munteanu, Mircea Ionuț Gheorghiță, Răzvan Mercuț, Elena Claudia Sin, Sanda Mihaela Popescu
Journal of Clinical Medicine.2023; 12(10): 3383. CrossRef
Bisphosphonates and osteonecrosis of the jaws: Clinical and forensic aspects
Diana Nogueira, Inês Morais Caldas, Ricardo Jorge Dinis-Oliveira
Archives of Oral Biology.2023; 155: 105792. CrossRef
Correlations between Immune Response and Etiopathogenic Factors of Medication-Related Osteonecrosis of the Jaw in Cancer Patients Treated with Zoledronic Acid
George Adrian Ciobanu, Laurențiu Mogoantă, Sanda Mihaela Popescu, Mihaela Ionescu, Cristina Maria Munteanu, Ionela Elisabeta Staicu, Răzvan Mercuț, Cristian Corneliu Georgescu, Monica Scrieciu, Daniel Vlad, Adrian Camen
International Journal of Molecular Sciences.2023; 24(18): 14345. CrossRef
Analysis of the Degree of Information of Dental Surgeons about Antiresorptive Drugs According to the Time Since Graduation in Dentistry
Flávia Godinho Costa Wanderley Rocha, Roberto Paulo Correia de Araújo
Pesquisa Brasileira em Odontopediatria e Clínica Integrada.2023;[Epub] CrossRef
Safety and Efficacy of Pamidronate in Neonatal Hypercalcemia Caused by Subcutaneous Fat Necrosis: A Case Report
Stefano Martinelli, Marco Pitea, Italo Francesco Gatelli, Tara Raouf, Graziano Barera, Ottavio Vitelli
Frontiers in Pediatrics.2022;[Epub] CrossRef
Zoledronic acid for osteoporosis and associated low-energy fractures
S. S. Rodionova, A. F. Kolondaev, A. N. Torgashin, I. A. Solomyannik
Meditsinskiy sovet = Medical Council.2022; (21): 163. CrossRef

Original Article

Clinical Study
Effects of Systemic Glucocorticoid Use on Fracture Risk: A Population-Based Study: Ji Weon Koh, Junkang Kim, Hyemin Cho, Yong-Chan Ha, Tae-Young Kim, Young-Kyun Lee, Ha Young Kim, Sunmee Jang; Endocrinol Metab. 2020;35(3):562-570. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.659

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Background
Long-term glucocorticoid use increases fracture risk by reducing bone mass. This study evaluated the relationship between hip and vertebral fractures and the total amount of systematic glucocorticoid use.
Methods
We randomly selected 1,896,159 people aged 20 to 100 years who participated in the National Health Checkup program in 2006. The amount of glucocorticoids prescribed was calculated based on the defined daily dose (DDD). The total DDD was obtained by adding oral and parenteral glucocorticoids for 6 months from the index date. Subjects were categorized into four groups according to total glucocorticoid DDDs: non-users (DDDs=0), low users (0< DDDs ≤45), intermediate users (45< DDDs ≤90), and high users (90< DDDs). We followed them for 2 years. A multivariate Cox proportional hazard model was used to evaluate the effects of the total amount of glucocorticoid use on hip and vertebral fractures.
Results
Higher glucocorticoid use was associated with a higher risk of vertebral fracture. Relative to non-users, the vertebral fracture risk was 1.39 times higher in the low-user group, 1.94 times higher in the intermediate-user group, and 2.43 times higher in the highuser group. The risk of hip fracture was 1.72 times higher in intermediate users and 3.28 times higher in high users than in non-users.
Conclusion
As the amount of glucocorticoid use for 6 months increased, the risk of hip and vertebral fractures became higher. In order to prevent fractures, it is necessary for doctors to evaluate the total amount of glucocorticoid prescribed to the patient and to provide appropriate treatment.

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Average daily glucocorticoid dose, number of prescription days, and cumulative dose in the initial 90 days of glucocorticoid therapy are associated with subsequent hip and clinical vertebral fracture risk: a retrospective cohort study using a nationwide h
Masayuki Iki, Kenji Fujimori, Shinichi Nakatoh, Junko Tamaki, Shigeyuki Ishii, Nobukazu Okimoto, Hironori Imano, Sumito Ogawa
Osteoporosis International.2024; 35(5): 805. CrossRef
Chronic airway disease as a major risk factor for fractures in osteopenic women: Nationwide cohort study
Sung Hye Kong, Ae Jeong Jo, Chan Mi Park, Kyun Ik Park, Ji Eun Yun, Jung Hee Kim
Frontiers in Endocrinology.2023;[Epub] CrossRef
Bad to the bones: prescribing of drugs for the prevention and treatment of osteoporosis in patients on chronic glucocorticoids
Sarah J. Billups, Vinh K Thai, Jacob Denkins, Ian C. Dettman, Micol S. Rothman
Archives of Osteoporosis.2023;[Epub] CrossRef
High Risk of Fractures Within 7 Years of Diagnosis in Asian Patients With Inflammatory Bowel Diseases
Hyung Jin Ahn, Ye-Jee Kim, Ho-Su Lee, Jin Hwa Park, Sung Wook Hwang, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Beom-Jun Kim, Sang Hyoung Park
Clinical Gastroenterology and Hepatology.2022; 20(5): e1022. CrossRef
Challenges in the diagnosis and management of glucocorticoid‐induced osteoporosis in younger and older adults
Madhuni Herath, Bente Langdahl, Peter R. Ebeling, Frances Milat
Clinical Endocrinology.2022; 96(4): 460. CrossRef
Comparative effectiveness of bisphosphonate treatments for the prevention of re-fracture in glucocorticoid-induced osteoporosis: protocol for a systematic review and meta-analysis
Hongmin Chu, Bo-Hyoung Jang, GaYoon Kim, Seowoo Bae, Hyeju Lee, Seonghee Nam, Jeonghoon Ahn
BMJ Open.2022; 12(9): e062537. CrossRef
Why Do We Need Proactive Management for Fracture Prevention in Long-Term Glucocorticoid Users?
Han Seok Choi
Endocrinology and Metabolism.2020; 35(3): 549. CrossRef

Special Article

Hypothalamus and Pituitary gland
Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement: Sang Ouk Chin, Cheol Ryong Ku, Byung Joon Kim, Sung-Woon Kim, Kyeong Hye Park, Kee Ho Song, Seungjoon Oh, Hyun Koo Yoon, Eun Jig Lee, Jung Min Lee, Jung Soo Lim, Jung Hee Kim, Kwang Joon Kim, Heung Yong Jin, Dae Jung Kim, Kyung Ae Lee, Seong-Su Moon, Dong Jun Lim, Dong Yeob Shin, Se Hwa Kim, Min Jeong Kwon, Ha Young Kim, Jin Hwa Kim, Dong Sun Kim, Chong Hwa Kim; Endocrinol Metab. 2019;34(1):53-62. Published online March 21, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.1.53

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The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach.

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Smart Materials in Medicine.2024;[Epub] CrossRef
Evaluation and Management of Bone Health in Patients with Thyroid Diseases: A Position Statement of the Korean Thyroid Association
A Ram Hong, Ho-Cheol Kang
Endocrinology and Metabolism.2023; 38(2): 175. CrossRef
Growth Hormone Excess: Implications and Management
Suneela Dhaneshwar, Shrishti Shandily, Vatsalya Tiwari
Endocrine, Metabolic & Immune Disorders - Drug Targets.2023; 23(6): 748. CrossRef
Revisiting the usefulness of the short acute octreotide test to predict treatment outcomes in acromegaly
Montserrat Marques-Pamies, Joan Gil, Elena Valassi, Marta Hernández, Betina Biagetti, Olga Giménez-Palop, Silvia Martínez, Cristina Carrato, Laura Pons, Rocío Villar-Taibo, Marta Araujo-Castro, Concepción Blanco, Inmaculada Simón, Andreu Simó-Servat, Gemm
Frontiers in Endocrinology.2023;[Epub] CrossRef
Evaluation and Management of Bone Health in Patients with Thyroid Diseases: a Position Statement from the Korean Thyroid Association
A Ram Hong, Hwa Young Ahn, Bu Kyung Kim, Seong Hee Ahn, So Young Park, Min-Hee Kim, Jeongmin Lee, Sun Wook Cho, Ho-Cheol Kang
International Journal of Thyroidology.2022; 15(1): 1. CrossRef
Octreotide in the treatment of acromegaly – the possibilities of high-dose therapy
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Meditsinskiy sovet = Medical Council.2022; (10): 148. CrossRef
Approach of Acromegaly during Pregnancy
Alexandru Dan Popescu, Mara Carsote, Ana Valea, Andreea Gabriela Nicola, Ionela Teodora Dascălu, Tiberiu Tircă, Jaqueline Abdul-Razzak, Mihaela Jana Țuculină
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Severe respiratory failure in a patient with COVID-19 and acromegaly: rapid improvement after adding octreotide
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Precision Therapy in Acromegaly Caused by Pituitary Tumors: How Close Is It to Reality?
Cheol Ryong Ku, Vladimir Melnikov, Zhaoyun Zhang, Eun Jig Lee
Endocrinology and Metabolism.2020; 35(2): 206. CrossRef
Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement
Sang Ouk Chin, Cheol Ryong Ku, Byung Joon Kim, Sung-Woon Kim, Kyeong Hye Park, Kee Ho Song, Seungjoon Oh, Hyun Koo Yoon, Eun Jig Lee, Jung Min Lee, Jung Soo Lim, Jung Hee Kim, Kwang Joon Kim, Heung Yong Jin, Dae Jung Kim, Kyung Ae Lee, Seong-Su Moon, Dong
The Korean Journal of Medicine.2019; 94(6): 485. CrossRef

Case Reports

A Case of Adult-Onset Adrenoleukodystrophy Combined with Moyamoya Disease.: Yong Cheol Kim, Byoung Hyun Park, Tae Yang Yu, Ae Ryoung Jin, Hye Jung Noh, Chung Yong Yang, Ha Young Kim, Chung Gu Cho; J Korean Endocr Soc. 2009;24(1):58-62. Published online March 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.1.58

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Abstract PDF

Adrenoleukodystrophy (ALD) is a rare inherited metabolic disease associated with the accumulation of very long chain fatty acids (VLCFA) in the central and peripheral nervous systems and adrenal glands, and leads to leukoencephaly myeloneuropathy, adrenal insufficiency, and hypogonadism. Frequent phenotypes, which account for 80% of cases, are infantile ALD and adrenomyeloneuropathy. Adult-onset ALD is rare (1~3%). The diagnosis of X-linked ALD is based on clinical findings and abnormal plasma concentrations of VLCFA. Here, we report a rare case of adult-onset ALD, which might involve a brain vascular operation as an aggravating factor, combined with moyamoya disease, in a 35-year-old male who presented with adrenal insufficiency, abnormal brain imaging, and elevated VLCFA levels.

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Clinical and Genetic Aspects in Twelve Korean Patients with Adrenomyeloneuropathy
Hyung Jun Park, Ha Young Shin, Hoon-Chul Kang, Byung-Ok Choi, Bum Chun Suh, Ho Jin Kim, Young-Chul Choi, Phil Hyu Lee, Seung Min Kim
Yonsei Medical Journal.2014; 55(3): 676. CrossRef
An Incidentally Identified Sporadic Case with Adrenoleukodystrophy with the ABCD1 Mutation
Soon-Jung Shin, Ja Hye Kim, Yoo-Mi Kim, Gu-Hwan Kim, Beom Hee Lee, Han-Wook Yoo
Journal of Genetic Medicine.2013; 10(1): 43. CrossRef

A Case of Pheochromocytoma That Presented as Inverted Takotsubo Cardiomyopathy.: Meyoung Cho, Ik Sang Shin, Ae Ryoung Jin, Jong Bin Park, Hye Jung Noh, Hun Soo Kim, Ha Young Kim, Byoung Hyun Park, Chung Gu Cho, Jin Won Jeong; J Korean Endocr Soc. 2009;24(1):47-53. Published online March 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.1.47

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Abstract PDF

A 52-year-old female was admitted to the hospital with abdominal pain. Her electrocardiogram revealed ST depressions in leads II, III, aVF and V2-5. The echocardiography showed transient cardiomyopathy with akinesia of the basal and mid portions of the left ventricle and hyperkinesia of the apex. There was no evidence of any vascular lesion on the emergency coronary angiography. She was diagnosed with pheochromocytoma by abdominal computed tomography and the post-operative pathologic examinations. These findings led us to a diagnosis of inverted Takotsubo cardiomyopathy related with pheochromocytoma. The recognition of such a rare cardiac manifestation should be considered in the diagnosis of pheochromocytoma, and especially in the circumstances of acute heart failure.

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A Case of Malignant Pheochromocytoma Presenting as Inverted Takotsubo-Like Cardiomyopathy
Jung Eun Jang, Hyuk Hee Kwon, Min Jung Lee, Chang Hee Jung, Sung Jin Bae, Hong Kyu Kim, Woo Je Lee
Endocrinology and Metabolism.2012; 27(1): 98. CrossRef

Original Articles

Serum Leptin Levels in Relation to Quantitative Ultrasound Values of Calcaneus in Korean Postmenopausal Women in Chung-Up District.: Sang Wook Kim, Jung Min Koh, Ha Young Kim, Duk Jae Kim, Ghi Su Kim; J Korean Endocr Soc. 2002;17(1):79-86. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Obese postmenopausal women usually have a tend to have greater bone mineral density than lean women. This has been attributed to either the mechanical effects of their excessive weight on bone tissue or to their high body fat content. A recent study demonstrated that leptin, the hormone produced in adipocytes, acts on bone metabolism. These findings have prompted speculations on the possible role of leptin in the protective effect of obesity on bone. METHEODS: We studied the relationship between serum leptin levels and quantitative ultrasound (QUS) values of calcaneus in 94 postmenopausal Korean women who were randomly selected from the population of the Chung-Up osteoporosis prevalence study. QUS values, broadband ultrasound attenuation and speed of sound; were measured at the calcaneus. RESULTS: Leptin values were strongly correlated with body mass index (r = 0.478, p< 0.001), confirming a positive relationship between leptin levels and fat mass. In contrast, no significant correlations were observed between serum leptin levels and calcaneal QUS values. CONCLUSION: Our results suggest that circulating plasma leptin does not have a significant influence on QUS values of calcaneus in Korean postmenopausal women.

Percutaneous Ethanol Injection in Autonomous Functioning Thyroid Nodules and Complex Cysts: Five Years' Experience.: Seong Jin Lee, Jung Hee Han, Ha Young Kim, Jong Chul Won, Sang Wook Kim, Ho Kyu Lee, Il Min Ahn; J Korean Endocr Soc. 2002;17(1):57-68. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Percutaneous ethanol injection therapy (PEI) performed with ultrasonography guidance has recently been used in cases of autonomous functioning thyroid nodules (AFTN) and benign complex cysts. We performed this study to analyze the effects of PEI on AFTN and benign complex cysts. METHEODS: From September 1995 to September 2000, we performed PEI on 456 outpatients (47 men and 409 women, mean age 42.4+/-11.8 years) with AFTN or benign complex cysts. All cases were subjected to fine needle aspirations (FNA) by ultrasonography-guidance if necessary. FNA was performed at least twice with results of colloid nodule in cases of complex cysts. For AFTN, cases with FNA results of follicular neoplasm were also included. After PEI on AFTN, patients were classified into three response groups: complete response as judged by our new criteria (CR, normalization of TSH and free T4, disappearance of hot nodule on thyroid scan) along with the old criteria of previous studies (normalization of TSH and free T4, recovery of suppressed extranodular tissue on thyroid scan), partial response (PR, normalized free T4 but suppressed TSH, persistent hot nodule despite recovery in suppressed extranodular tissue) and no response (no change of hot nodule). Complex cysts were classified into three groups in accordance with volume reduction after PEI: complete response (CR, above 90% of volume reduction), partial response (PR, 50~89%) and no response (below 50%). RESULTS: Overall pre-treatment volumes were 15.3+/-12.1 mL and post-treatment volumes were 2.8+/-2.9 mL, with 66.4+/-19.9% of volume reductions in AFTN and complex cysts. Volume reductions were 71.5+/-18.0% in AFTN, and 66.1+/-15.0% in complex cysts. In 24 cases of AFTN, responses satisfying the previous criteria were 14 (58.3%) of CR, 6 (25.0%) of PR, and 4 (16.7%) of no response. However, by the new criteria there were 1 (4.2%) of CR, 10 (41.6%) of PR, and 13 (54.2%) of no response. In 432 cases of complex cysts, CR was observed in 82 (19.0%), PR in 261 (60.4%) and no response in 89 (20.6%). The volume reductions in complex cysts with pre-treatment volume larger than 15 mL were higher than those of groups with smaller volumes (p<0.001). Pre-treatment volumes were not correlated with post-treatment volumes, nor with volume reductions. Volume reductions were not correlated with the amounts of injected ethanol. Mild and transient complications were observed in 41 cases (9.0%) during PEI, consisting of transient neck pain (n=36, 7.9%), transient unilateral vocal cord palsy (n=3, 0.7%), intracavitary hemorrhage (n=1, 0.2%), and transient hypotension (n=1, 0.2%). CONCLUSION: Our data suggest that the efficacy of PEI on AFTN is temporary and does not usually induce long-term complete remissions. In complex cysts, however, PEI may have potential as an additive treatment modality to thyroid hormone suppressive therapy

Effects of Glucocorticoid on Apoptosis of Human Bone Marrow Osteogenic Stromal Cells.: Ha Young Kim, Duk Jae Kim, Si Yeol Lee, Jeong Soo Hong, Dong Kwan Kim, Ghi Su Kim; J Korean Endocr Soc. 2002;17(1):23-31. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Osteoporosis is one of the most serious side effects of long-term glucocorticoid therapy, but the mechanism of glucocorticoid-induced bone loss remains poorly defined. Glucocorticoid induces decreased bone formation and death of isolated segments of bone (osteonecrosis) suggesting that glucocorticoid excess may affect the birth or death rate of bone cells and thereby reduce their numbers. It has been known that reduction in bone formation is due to reduced proliferation in osteoblast precursor cells and reduced matrix synthesis in mature osteoblast. Here, we present evidence for dexamethasone-induced apoptosis on human bone marrow stromal cells (hBMSC). To understand the mechanism of glucocorticoid-induced osteoporosis, we investigated the effects of glucocorticoid on primary cultured hBMSC. METHEODS: Treatment with dexamethasone at the concentration of 10-9 M for 3~5 days significantly decreased cleavage tetrazolium salt WST-1 level/concentration by mitochondrial dehydrogenase in viable cells. Greater decrease was observed with higher concentration of dexamethasone (10-7 M, and 10-5 M). Apoptosis was measured by annexin V binding/propidium iodide using fluorescence-activated cell sorter (FACS) analysis and nuclear morphology stained with the fluorescence dye, Hoechst 33342. RESULTS: The level/concentration of apoptotic hBMSC (annexin V positive / PI negative) was increased with 10-9 M dexamethasone (1.2% to 5.3%) and further increased with 10-7 M, and 10-5 M concentration (11.7% and 12.5%, respectively). The same result was observed with Hoechst 33342 staining. CONCLUSION: These results indicate that glucocorticoid induces apoptosis on osteoblast precursor cell, hBMSC, and may contribute to decrease bone formation

Clinical Applications of 18-FDG PET in Recurred Differentiated Thyroid Cancer with Negative 131I Whole Body Scintigraphy: A Comparative Analysis with 99mTc-MIBI Scintigraphy.: Jong Chul Won, Sung Jin Lee, Tae Yun Lee, Il Seong Nam-Goong, Sy Yeol Lee, Ha Young Kim, Jung Hee Han, Jin Sook Ryu, Dae Hyuk Moon, Il Min Ahn; J Korean Endocr Soc. 2001;16(4-5):481-493. Published online October 1, 2001

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Abstract PDF: BACKGROUND
In patients with differentiated thyroid cancer treated by surgery and radioactive iodine ablation, serum thyroglobulin(Tg) and 131I whole body scan(WBS) are recognized as being the best cooperative indicators for detection of recurrence or metastasis. However, in some cases, 131I WBS shows no specific lesions despite elevated serum Tg. Therefore, 18-Fluorine-fluorodeoxyglucose (FDG) positron emission tomography(PET) has emerged as a useful method for the detection of 131I WBS negative thyroid cancers. The aims of the present study are to evaluate the clinical usefulness of this technique in detection and to compare the results with 99mTc-MIBI scintigraphy(MIBI) in cases of final results being confirmed by histologic diagnosis and other imaging methods. METHODS: We conducted a retrospective analysis amon 131I WBS negative recurred papillary thyroid carcinoma patients(male: female ratio=9:22, median age=42 yr). FDG PET was performed in 28 patients and MIBI 28 patients, 25 of whom were common to both groups. All patients had histologically proven recurrence/metastasis and negative 131I WBS results but persistently elevated serum Tg levels. In each case overall clinical evaluations were performed including histology, cytology, thyroglobulin level, other imaging methods, posttherapy 131I WBS and subsequent clinical course, to allow comparison with the results of FDG PET. RESULTS: In 19 cases of patients with negative 131I WBS, proven recurrence/metastasis lesions were detected in FDG PET. Compared with MIBI, FDG PET was found to be superior in 8 cases(including 2 patients with distant metastases). No FDG-negative/MIBI-positive tumor was observed. One FDG PET negative and MIBI negative case was proven 3 months later to be metastatic cervical lymph nodes, Sensitivities were 94.7% in the FDG PET group and 52.6% in MIBI. Diagnostic accuracy of FDG PET was superior to that of MIBI(93% vs. 62%, respectively, p=0.003). CONCLUSION: Our results confirmed the clinical usefulness of FDG PET for detection of 131I negative differentiated thyroid cancers and suggested the value of FDG PET as an initial diagnostic step, rather than MIBI, in these cases.

Effectiveness of Percutaneous Ethanol Injection in Benign Cold Thyroid Nodules: Five Years' Experience.: Seong Jin Lee, Jung Hee Han, Ha Young Kim, Jong Chul Won, Sang Wook Kim, Ho Kyu Lee, Il Min Ahn; J Korean Endocr Soc. 2001;16(2):210-220. Published online April 1, 2001

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Abstract PDF: BACKGROUND
Percutaneous ethanol injection therapy (PEI) which is performed with the guidance of ultrasonography has recently been used in patient who had benign cold thyroid nodules. We performed this study to analyze the long-term effects of PEI on benign cold thyroid nodules. METHOD: From September 1995 to September 2000, we treated 198 outpatients (12 men and 186 women, who had a mean age of 40.8 years, with a range of 15-71) who had benign cold thyroid nodules at the Asan Medical Center. The PEI was performed on 141 patients who had solitary nodules (SN) and on 57 patients who had prominent nodules or Questionable or typing error? multiple nodules (MN). All patients had fine needle aspirations (FNAs) at least twice which resulted in a diagnosis of the presence of a colloid nodule. Thyroid hormone was given to all patients along with TSH measurements. The thyroid hormone dose was titrated to correspond to TSH level of a low normal range. These patients were followed up for mean period of 37.6 months (range 18-60). Patients who were treated with PEI were classified into three groups according to their volume reduction: a complete response (CR, which was above 90% in volume reduction), a partial response (PR, which was a 50-89%) reduction and No Response (which was below 50% or an increased size) groups. RESULTS: The overall pre-treatment volumes of the nodules were 15.7+/-19.8 mL. The overall post-treatment volumes were 2.4+/-2.6 mL and consisted of volume reductions of 70.1+/-17.1%. The results of PEI for all of the patients were: a complete reduction (CR) in 34 cases (17.2%), a partial reduction (PR) in 142 cases (71.7%) and No Response in 22 patients (11.1%). In 141 patients in the SN group, in which there was a mean follow-up duration of 36.7+/-11.2 months, the volume reductions were 68.3+/-18.8%. CR was observed in 20 patients (14.2%), PR in 103 (73.0%) and No Response in 18 (12.8%). In twenty-two of the SN patients (22/141, 15.6%) we were able to discontinue the thyroid hormone suppressive therapy because those nodules had markedly decreased in volume after PEI without any further increase of nodule size during the follow-up period. In 57 patients in the MN group, over a mean follow-up durations of 37.1+/-11.4 months, the volume reductions were 74.3+/-12.1%. CR was observed in 14 patients (24.6%), PR in 39 (68.4%) and No Response occurred in 4 (7.0%). During the follow-up period after PEI, further volume reductions were observed for 36 months after thyroid hormone suppressive therapy in the Response Group. Differences in volume reductions between the SN and MN groups were not statistically significant but the volume reductions in patients who had a pre-treatment volume larger than 15 mL were higher than those in the smaller group (p<0.001). In the cases of the SN and MN groups, volume reductions did not correlate with either the amount of injected ethanol or the pre-treatment volumes, but the pre-treatment volumes correlated with post-treatment volumes in the patients who had SN (p<0.001, r=0.411) and MN (p<0.001, r=0.729). We observed mild, but transient complications in 32 patients (16.2%) during PEI which included a transient neck pain (n=27, 13.6%), a transient unilateral vocal cord palsy (n=4, 2.0%), and an abscess formation (n=1, 0.5%) which was cured. CONCLUSION: These results suggest that PEI is a feasible adjunctive therapy to use in thyroid hormone suppressive therapy for benign cold thyroid nodules

Differential Diagnostic Value of TSH Receptor Antibody Measurements in Thyrotoxic Postpartum Patients with History of Graves' Disease.: Seong Jin Lee, Yun Ey Chung, Ha Young Kim, Jung Hee Han, Jong Chul Won, Ahm Kim, Jin Sook Ryu, Dae Hyuk Moon, Il Min Ahn; J Korean Endocr Soc. 2001;16(1):75-84. Published online February 1, 2001

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Abstract PDF: BACKGROUND
It is known that pregnancy markedly influences the clinical course of autoimmune thyroid diseases. In the postpartum period, various kinds of autoimmune thyroid dysfunctions can be observed. Thyroid dysfunction is found in 5.5-7.1% of postpartum women in the general population. Among those who show thyroid dysfunction after delivery, some will develop Graves' disease and others will develop postpartum thyroiditis. It is also known that patients with Graves' disease may manifest thyrotoxicosis in the postpartum period because of postpartum thyroiditis or relapse of the Graves' disease itself. We evaluated the clinical features of postpartum thyrotoxicosis in Graves' disease patients to find diagnostic indices that could be used in differentiating between postpartum thyroiditis and relapse of Graves' disease. METHOD: We reviewed the cases with postpartum thyrotoxicosis in patients that had a history of Graves' disease between 1995 and 2000. The diagnosis of postpartum thyroiditis had been made by means of a 99mTc thyroid scan or by the observation of a typical triphasic thyroid function change, in cases where a 99mTc thyroid scan was not possible because of breast feeding. We measured the serum TSH, free T4, free T3, TSH binding inhibiting immunoglobulin (TBII), anti-thyroid peroxidase (TPO) antibody, and anti- thyroglobulin (Tg) antibody serially from the time of the diagnosis of Graves' disease to the time of postpartum thyroid dysfunction. RESULTS: Eleven patients, 5 patients in the postpartum thyroiditis (PPT group) and 6 patients with relapse of the Graves' disease (GD group), were identified. The mean values of TBII of two groups at the time of diagnosis of Graves' disease were 40.9+/-4.8 IU/mL (PPT group), 58.9+/-23.5 IU/mL (GD group) respectively, which were insignificant. The mean values of TBII of the two groups at early pregnancy were 3.2+/-1.9 IU/mL (PPT group), 41.6+/-22.6 IU/mL (GD group) and this difference was statistically significant (p=0.009). The mean values of TBII of the two groups at the time of postpartum thyrotoxicosis were 1.9+/-1.6 IU/mL (PPT group), 51.5+/-23.2 IU/mL (GD group) which were also statistically significant (p=0.003). The mean values of anti-TPO antibody, anti-Tg antibody, disease duration, and treatment duration between the two groups were not significantly different. The onsets of thyroid dysfunction after delivery in the two groups were 2.6+/-2.0 (PPT group), 4.0+/-3.9 (GD group) months which were statistically insignificant. CONCLUSION: These data suggest that the measurement of TBII at the time of the postpartum thyrotoxic period, could help to differentiate postpartum thyroiditis from a relapse of Graves' disease in those patients that have a history of Graves' disease especially when thyroid scan is not possible because of breast feeding.

The Role of Preoperative and Postoperative Thyroglobulin Measurements in The Detection of Well Differentiated Thyroid Carcinomas Recurrence.: Seong Jin Lee, Jong Chul Won, Ha Young Kim, Jung Hee Han, Eun Ju Lee, Sang Wook Kim, Jin Sook Ryu, Dae Hyuk Moon, Suk Joon Hong, Il Min Ahn; J Korean Endocr Soc. 2000;15(4-5):542-553. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Thyroglobulin (Tg) measurement is primarily used to monitor patients with well differentiated thyroid carcinomas (WDTC) for tumor recurrence. We evaluated the correlations between fold responses of thyroglobulin levels and TNM stages (and MACIS scores) at recurrent group. Also correlations between preoperative Tg levels and Tg (on or off replacement) levels at the time of recurrence were evaluated. Postoperative Tg levels between recurrent and non-recurrent groups were analyzed for the use of assessing risk of recurrence. METHODS: One hundred twenty five cases of WDTC who had total thyroidectomy and (131)I remnant thyroid ablation were finally included in this study. After optimal TSH stimulations (>30 microIU/mL), (131)I whole body scan (WBS) was performed. We interpreted as a recurrence only when abnormal findings on the (131)I WBS were detected. Preoperative, immediate postoperative and follow-up Tg tlevels were regularly measured. RESULTS: Difference of preoperative Tg levels between recurrent and non-recurrent groups was not significant (27.5+/-4.2 ng/mL vs. 16.0+/-10.9 ng/mL). Also differences of immediate postoperative Tg (on or off replacement) levels between two groups was not significant (2.4+/-3.8 ng/mL vs. 3.6+/-3.l ng/mL, 33.4+/-4.8 ng/ml vs. 24.5+/-4.8 ng/mL, respectively). Tg levels on replacement at 24 months after surgery between recurrent and non-recurrent groups were significantly different (2.2+/-4.8 ng/mL, 15.9+/-6.5 ng/mL, p<0.001) and also Tg levels off replacement between recurrent and non-recurrent groups were significantly different (4.0+/-6.6ng/mL vs. 49.4+/-9.3 ng/mL, p<0.001). Fold responses between recurrent and non-recurrent groups were significantly different (2.0+/-3.1 ng/mL, 5.0+/-4.1 ng/mL, p=0.009). Fold responses between recurrent and non- recurrent groups were significantly different according to TNM stages (p=0.002) but not different according to MACIS scores. Preoperative Tg levels were correlated Tg (on or off replacement) levels at the time of recurrence (p=0.02, r=0.4: p<0.001, r=0.6, respectively). Sensitivity, specificity, accuracy of Tg levels over 2 ng/mL on replacement were 95%, 73%, 84% but those of Tg levels over 7 ng/mL off replacement were 83%, 70%, 77%. CONCLUSION: Fold responses may predict prognosis of WDTC. Small postoperative increase in serum Tg levels may indicate a large increase of tumor mass in cases of normal or low preoperative Tg levels. Tg levels over 2 ng/mL on replacement or 7 ng/mL off replacement during follow-up may suggest the recurrence of WDTC.

Review Article

Oxidative Stress and Atherosclerosis.: Ha Young Kim, Joong Yeol Park; J Korean Endocr Soc. 2000;15(1):1-14. Published online January 1, 2001

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Abstract PDF: No abstract available.

Original Articles

FDG-PET as a Predictor of Recurrence with 131I Scan Negative Differentiated Thyroid Cancer: An Evaluation Compared with Pathologic Findings.: Eunju Lee, Sung Jin Lee, Cheol Ryoung Lee, Ha Young Kim, Hun Ho Song, Young So, Jin Sook Ryu, Dae Hyuk Moon, Suk Joon Hong, June Kkey Chung, Il Min Ahn; J Korean Endocr Soc. 1999;14(3):520-530. Published online January 1, 2001

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Abstract PDF: BACKGROUND
FDG-PET has been suggested to have a supplementary role in localizing recurred sites of differentiated thyroid carcinoma. This study was performed to show whether FDG-PET is feasible as an alternative diagnostic modality for patients with I-131 scan negative thyroid carcinoma by verification of post-surgical pathology findings. METHODS: Eighteen patients of papillary thyroid carcinoma (M:F=4:14, age 41+/-16 year) who had total thyroidectomy and I-131 ablation therapy were included. All patients showed negative I-131 scan on therapeutic dose but they were suspected as disease recurrence because of elevated serum Tg or anti-Tg Ab during follow-up periods. FDG-PET was performed, and then cervical lymph node dissection on either side or both sides of the neck was done according to FDG-PET results. RESULTS: A total of 77 cervical lymph node groups were dissected in 18 patients; internal jugular chain 49, spinal accessory 9, jugulodigastric 5, anterior jugular 4, paratracheal 3, supraclavicular 2, and others 5. Forty eight lymph node groups revealed metastatic papillary carcinoma on pathology and their largest diameter ranged from 0.4 to 7.0cm (1.2+/-0.7cm). All patients had at least one malignant lymph node group. FDG-PET detected 37 among 48 malignant lymph nodes (sensitivity 77%), and their count ratio ranged 1.7-31.1 (6.1+/-6.3). Among the 30 malignant lymph nodes less than 1cm, FDG-PET detected 20 lymph nodes. Of the 29 lymph node groups without malignant cells, FDG-PET was also negative in 24 groups (specificity S3%). Positive predictive value of FDG-PET on I-131 scan negative differentiated thyroid carcinoma was 88%; negative predictive value was 69%. CONCLUSION: FDG-PET has been confirmed as a valuable diagnostic modality to detect cervical lymph nodes of differentiated thyroid carcinoma who are suspicious for recurrence but with negative I-131 scan, by pathologic findings.

Clinical Significance of Human Sodium Iodide Symporter mRNA Expressions in Primary and Metastatic Papillary Thyroid Carcinoma.: Seong Jin Lee, Hyun Joo Park, Eun Ju Lee, Ha Young Kim, Jin Kyu Koh, Ki Young Park, Sung Bae Kim, Gyung Yup Gong, Suk Joon Hong, Il Min Ahn, Sang Hee Kim; J Korean Endocr Soc. 1999;14(3):514-519. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The iodide transport into thyroid cells is an essential step in the biosynthesis of thyroid hormones. The sodium iodide symporter (NIS) which is responsible for iodide transport was cloned recently and identified as a plasma membrane glycoprotein. Recent report suggested the absence of human NIS (hNIS) mRNA expression of papillary carcinoma in thyroid indicates absence of response on radioiodine therapy for distant metastasis. To understand the change of hNIS expression at the stage of metastasis in papillary thyroid carcinomas, we evaluated the expression levels of hNIS mRNA in primary and lymph node metastatic papillary carcinoma tissues. METHODS: Seven pairs of primary and lymph node metastatic tissues were included in this study. The level of hNIS mRNA in lymph node metastatic tissues and primary tissues were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). The level of GAPDH mRNA was used as internal control. RESULTS: Two among 6 lymph node metastatic tissues did not show hNIS mRNA even with significant hNIS expressions in papillary carcinoma tissues in thyroid. The levels of hNIS expression of remaining 4 lymph node metastatic tissues were lower than those of corresponding primary tissues. Interestingly, one case showed no hNIS expression in primary tissue, but significant hNIS expression in lymph node metastatic tissue. There was no correlation in hNIS mRNA expression between primary and lymph node metastatic tissues. CONCLUSION: No correlation was found in hNIS mRNA expression between primary and lymph node metastatic tissues, suggesting the measurements of hNIS mRNA level in primary tissues may not predict therapeutic response to radioactive iodine.

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