Endocrinology and Metabolism

Volume 16(4-5); October 2001

Review Articles

Role of BMP-2 in Osteoblast Differentiation.: Hyun Mo Ryoo; J Korean Endocr Soc. 2001;16(4-5):393-400. Published online October 1, 2001

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Abstract PDF: No abstract available.

Monitoring Therapy for Osteoporosis with Bone Densitometry.: Seoung Oh Yang, Soo Youn Ham; J Korean Endocr Soc. 2001;16(4-5):401-412. Published online October 1, 2001

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Abstract PDF: No abstract available.

Polycystic Ovary Syndrome and Women Health.: In Ju Kim; J Korean Endocr Soc. 2001;16(4-5):413-421. Published online October 1, 2001

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Abstract PDF: No abstract available.

Editorial

The Effects of Etidronate on Bone Loss after Renal Transplantation.: Sung Kil Lim; J Korean Endocr Soc. 2001;16(4-5):422-425. Published online October 1, 2001

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Original Articles

Effect of Intermittent Etidronate Therapy on the Prevention of Bone Loss after Kidney Transplantation.: Hye Soo Kim, Jong Min Lee, Sung Kwon Kim, Cheol Whee Park, Chul Woo Yang, Moo Il Kang, Suk Young Kim, Sung Koo Kang, Byung Kee Bang; J Korean Endocr Soc. 2001;16(4-5):426-437. Published online October 1, 2001

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Abstract PDF: BACKGROUND
Osteopenia or osteoporosis is one of the most frequently encountered complications in patients receiving various immunosuppressants after kidney transplantation. The few available preventive strategies for these complications tend to result in various outcomes. In this study, we evaluated the effect of intermittent etidronate therapy for the prevention of bone loss after kidney transplantation. METHODS: Fifty patients who received kidney transplantation for various reasons were recruited and followed for one year. Thirty-eight of these patients commenced etidronate treatment 7 days after operation, the other 12 were followed without etidronate therapy. The treatment consisted of 400mg of etidronate administered orally for 14 days, then repeated four-times every three months. Blood chemistry, iPTH and aluminium levels were tested periodically in all patients. Also checked were bone mineral density of the lumbar spine(L2-4) and femur at baseline, 6 and 12 months after kidney transplantation, as well as D-L spine lateral x-ray at baseline and 12 months. Serum osteocalcin and urine deoxypyridinoline were measured at baseline, 7 days and then every 3 months. RESULTS: Both the etidronate-treated and control groups showed significant decreases in bone mineral densities of the lumbar spine, femur neck and total femur at 6 and 12 months after kidney transplantation(p<0.005). Bone loss was significantly lower in the etidronate-treated group than the control at 12 months after kidney transplantation; lumbar spine(-3.54% vs. -9.51%, p<0.0005), femur neck (-5.41% vs. -8.91%, p<0.0005), total femur (-7.59% vs. -9.07%, p<0.005). Osteocalcin was decreased and deoxypyridinoline increased in both groups. No significant differences in the level or pattern of osteocalcin and deoxypyridinoline were observed in either group. New radiologic compression fractures were found in two patients of the treated group who exhibited severe osteoporosis at baseline during follow-up. CONCLUSIONS: The intermittent administration of etidronate seems to be effective in preventing rapid bone loss after kidney transplantation. Furthermore, this method is safe and convenient for administration and follow-up. Further studies will be required to elucidate the most effective treatment course for the prevention of fractures after kidney transplantation, especially in patients with established severe osteoporosis.

The Significance of Plasma ADH in Differential Diagnosis of Central Diabetes Insipidus.: Ho Jong Lee, In Myung Yang, Sun Kee Min, Jung Hyun Noh, Cheol Young Park, Seung Joon Oh, Deog Yoon Kim, Jung Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi; J Korean Endocr Soc. 2001;16(4-5):438-446. Published online October 1, 2001

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Abstract PDF: BACKGROUND
Although the water restriction test(WRT) has been used as a standard test for the differential diagnosis of diabetes insipidus(DI), the measurement of plasma ADH concentration is also known to be useful method for differential diagnosis. Recent studies have shown that some patients with idiopathic central DI(CDI) were found to have a lesion on follow-up imaging studies. There have been no report in Korea on plasma ADH measurement for the differential diagnosis of DI, nor on follow-up imaging study of the idiopathic CDI. METHODS: We retrospectively reviewed the clinical and laboratory findings of 26 patients(12 men, 14 women, age 9-65 years) with CDI, including pituitary MRI or CT scan, who had been diagnosed with WRT and had undergone plasma ADH concentration measurement. RESULTS: 1) Clinical features of the patients with complete CDI did not differ from those of patients with partial CDI. 2) Maximal urine osmolality of complete CDI and partial CDI were 168+/-69mOsm/kg and 431+/-141mOsm/kg, respectively, and the percentage increase in the urinary osmolality after ADH injection was 209+/-149% and 29+/-17%, respectively. 3) Among the 26 patients, 10 patients had their plasma ADH measured. Nine patients in this group were diagnosed as CDI by WRT and plasma ADH concentration of the 9 was compatible for CDI. The plasma ADH level was also inappropriately low in one patient who had been diagnosed with primary polydipsia by WRT, the patient was diagnosed as partial CDI. 4) The findings of follow-up MRI revealed isolated thickening of the pituitary stalk in two cases of idiopathic CDI diagnosed initially with MRI. CONCLUSION: This study suggests that the measurement of plasma ADH can ensure a better differential diagnosis between partial CDI and primary polydipsia, and that the patients with idiopathic CDI should be examined regularly with MRI brain scan, including the pituitary gland.

Usefulness of Thallium-201 Scintigraphy for Differentiating Benign and Malignant Thyroid Nodules in Inconclusive Cases with Fine Needle Aspiration.: Young Sil Lee, Chang Won Lee, Mi Hwa Jang, Ju Won Seok, Seok Man Son, Seok Dong Yoo, In Joo Kim, Yong Ki Kim; J Korean Endocr Soc. 2001;16(4-5):447-456. Published online October 1, 2001

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Abstract PDF: BACKGROUND
Although fine needle aspiration(FNA) is recognized as the most accurate procedure in the differential diagnosis of thyroid nodules, about 20~30% of nodules remain inconclusive in FNA. Therefore, we assessed the usefulness of Thallium-201 scintigraphy in differentiating benign from malignant thyroid nodules in patients with inconclusive diagnosis by FNA. METHODS: We studied 43 patients with inconclusive diagnosis(29 of follicular neoplasm, 11 of cystic change and 3 of inadequate) by FNA, with the results being confirmed histopathologically by operation. Thallium-201 scintigraphy was performed at 15 minutes(early scan) and 2-3 hours(late scan) after the intravenous administration of 37 MBq of thallium-201. Malignant nodules were defined by the retention of Thallium-201 on delayed images. RESULTS: In the 43 patients with inconclusive FNA diagnosis, Thallium-201 scan had a sensitivity of 75.0%, specificity of 62.9% and accuracy of 65.1%. The positive and negative predictive values were 31.6% and 91.7%, respectively. In the 29 patients with follicular neoplasm by FNA, Thallium-201 scan had a sensitivity of 83.3%, specificity of 60.9% and accuracy of 65.5%. The positive and negative predictive values were 35.7% and 93.3%, respectively. CONCLUSION: In particular, Thallium-201 scintigraphy demonstrated a high negative predictive value, Therefore, for patients with inconclusive FNA findings, Thallium-201 scintigraphy might be useful in differentiating between benign and malignant thyroid nodules, and has the potential to reduce the rate of unnecessary operations in benign nodules.

The Changes of Expression of Thyroid Specific Antigens in Aging.: Young Joo Park, Eun Shin Park, Tae Yong Kim, Sang Wan Kim, Hyeong Kyu Park, Do Joon Park, Won Bae Kim, Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Sang Chul Park, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2001;16(4-5):457-466. Published online October 1, 2001

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Abstract PDF: BACKGROUND
With the prevalence of serum antithyroglobulin(anti-TG) and antithyroperoxidase(anti-TPO) autoantibodies increasing with age, it has been suggested that changes of thyroid autoimmunity with aging are associated with endemic iodine intake. To understand the mechanism of aging-related increases of thyroid autoimmune response, we investigated the expression of thyroid specific autoantigens of aged phenotype, and compared them with those of young phenotype both in vivo and in vitro. METHODS: Sprague-Dawley rats were sacrificed at 5, 10 and 16 weeks(young), and at 23 months(aged). Their FRTL-5 thyroid cells were harvested at cell passages less than 10(fresh) or more than 30 (aged). The expression of thyroid autoantigens, sodium-iodide symporter(NIS), TSH receptor (TSHR), TG and TPO, were examined by northern blot analysis. To evaluate the effects of iodide, 1mM of NaI was added to the medium for 24 hours, and following incubation the expressions of MHC class I and class II were also examined. RESULTS: The expressions of TPO were markedly increased in the aged rats, and those of TG were moderately. However, NIS and TSHR showed no differences in their expression levels between aged rats and young rats. In vitro, there were no differences in the expressions of TG or TPO, nor of NIS or TSHR, between aged cells and fresh cells. Neither did Iodide exhibit any influence on the expression of MHC molecules in aged cells or fresh cells. CONCLUSION: The expression levels of TPO and TG were increased in aged rats, which may partially explain the mechanism of increasing thyroid autoimmunity with age.

Expression of the MAGE-1, -2, -3, -4, -5, and -10 Genes in Thyroid Cancers.: Young Sik Choi, Hark Rim, Yo Han Park, Kang Dae Lee, Jae Hwa Lee, Hee Kyoung Chang; J Korean Endocr Soc. 2001;16(4-5):467-480. Published online October 1, 2001

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Abstract PDF: BACKGROUND
MAGE(melanoma antigen gene) has been named as cancer/testis specific antigens since its expression is only detected in the testis or cancer cells. Because of its relatively specific expression in cancer cells, it has been considered as a marker for the early diagnosis of several cancers, or as an appropriate target for a specific immunotherapy mediated by cytotoxic T lymphocytes. Therefore, there have been many reports concerning the expression of MAGE genes in various types of malignant tumors, although only a few reports in human thyroid neoplasms. The purpose of this study was to determine whether the MAGE-1, -2, -3, -4, -5, and -10 genes expressed in different histological types of thyroid tumors and to elucidate the clinical usefulness of MAGE genes on the diagnosis of thyroid tumors. METHODS: Thirty-eight patients who had undergone thyroidectomy at Kosin Medical Center between January and August, 1999 were included in the study. Of the 38 patients enrolled, 26 exhibited papillary carcinoma, 3 papillary carcinoma with lymph node metastasis, 1 follicular carcinoma, 1 medullary carcinoma, 5 nodular hyperplasia, 1 adenomatous goiter, and 1 follicular carcinoma. In the twelve normal control thyroid tissues, total cellular mRNA was extracted from 31 cancer tissues and 7 benign tissues, RT-PCR was run in 35 cycles, with specific primers of the subtypes of MAGE genes. With probes confirmed by DNA sequencing, the isolates were reevaluated by Southern blot hybridization. RESULTS: In the 26 papillary carcinomas, MAGE-1,-2,-3,-4,-5 and -10 genes were expressed in 88.5%, 92.3%, 3.8%, 26.9%, 26.9%, and 0% by RT-PCR respectively. In the three papillary carcinomas with regional lymph node metastasis, MAGE-1, -2 and -5 genes expressed in two of the three, and MAGE-4 in one of the three cases. In the one medullary carcinoma, the MAGE-1,-2,-4, and MAGE-5 genes were expressed, and in the one case of follicular carcinoma, only the MAGE-2 gene was expressed. In contrast, none of the 7 benign tumors and 12 normal control tissues expressed any of these MAGE genes. The sensitivity of MAGE-1,-2,-3,-4,-5 and -10 genes in thyroid tumors was 83.8%, 90.3%, 3%, 29.0%, 32.3%, and 0%, respectively and the specificity was 100%. CONCLUSION: These results demonstrate that MAGE genes were expressed in the malignant thyroid tumors but not in the benign tumors and normal tissues. Among the MAGE gene families, MAGE-1 and -2 genes were more sensitive than MAGE-3, 4,-5 and -10 genes. However, in order to demonstrate if the MAGE genes could be used for the diagnosis of follicular carcinoma and distant metastasis in thyroid tumors, further study is required.

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.

Case Reports

Papillary Thyroid Cancer Arising in Lateral Aberrant Thyroid Presenting with Multiple Metastases.: Nam Il Cheon, Chang Hun Lee, Se In Hong, Jin Ook Chung, In Seok Yoon, Dong Hyeok Cho, Ho Cheol Kang, Dong Jin Chung, Min Young Chung; J Korean Endocr Soc. 2001;16(4-5):494-501. Published online October 1, 2001

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Abstract PDF: Carcinoma of the thyroid usually presents as a palpable thyroid mass. However, in rare cases patients with thyroid cancer present with metastases of the cervical lymph node as the initial manifestation. The metastatic papillary tumor in cervical lymph nodes stained positive for thyroglobulin indicates the presence of a thyroid carcinoma, usually in the ipsilateral lobe. We herein report a case of multiple metastases in papillary thyroid carcinoma arising in the lateral aberrant thyroid with no evidence of thyroid carcinoma in the thyroid lobe.

A Case of Cured Diabetes Mellitus after Pheochromocytoma Removal.: Chang Kyun Hong, Yu Bae Ahn, Sul Hye Kim, Young Sik Woo, Seoung Goo Lee, Seung Hyun Ko, Ho Ki Song, Kun Ho Yoon, Moo Il Kang, Bong Yeon Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; J Korean Endocr Soc. 2001;16(4-5):502-507. Published online October 1, 2001

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Abstract PDF: Pheochromocytoma is usually associated with a combination of various clinical manifestations caused by the overproduction of catecholamines. It is frequently accompanied by impaired glucose tolerance operating through 2-and-adrenergic mechanisms. A 41-year-old-woman was admitted to the hospital because of poorly-controlled diabetes mellitus and hypertension. She had suffered intermittent paroxysmal attacks of headache and chest discomfort and had been treated intermittently over a 2 year period for diabetes mellitus and hypertension. At admission, the levels of serum epinephrine, norepinephrine urinary excretion of total metanephrine, and VMA were all abnormally elevated. Adrenal CT showed a well-defined, homogenous mass in the right adrenal region and the tumor was diagnosed as pheochromocytoma. After tumor resection, the increased blood level of catecholamines, the urinary excretion of total metanephrine, and VMA were normalized, as was the hyperglycemia state. Diabetes mellitus of the patient was considered permanently resolved after tumor removal by the result of glucose tolerance in 75g oral glucose tolerance test.

Two Cases of Autoimmune Insulin Syndrome with Hypoglycemia.: See Hyung Park, Shin Won Lee, Gui Hwa Jeong, Chang Hoon Choi, Soon Hee Lee, Jeung Hoon Han, Jeong Guk Kim, Seong Woo Ha, Bo Wan Kim; J Korean Endocr Soc. 2001;16(4-5):508-513. Published online October 1, 2001

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Abstract PDF: Autoimmune insulin syndrome is characterized by insulin autoantibody, hyperinsulinemia, and fasting hypoglycemia without previous insulin immunization. This syndrome shows discordant levels between immunoreactive insulin and C-peptide. Negative results of an anatomic study of the pancreas and an inability to reproduce hypoglycemia during a prolonged fast may be helpful in excluding insulinoma. Symptomatic hypoglycemia usually develops during an oral glucose tolerance test. This syndrome is a self-limited disorder. Recently, we experienced one case that developed symptomatic hypoglycemia during both the fasting & oral glucose tolerance test, and another that developed symptomatic hypoglycemia during the oral glucose tolerance test but not the fasting test. Hereby, we present these cases with a review of the literature.

A Case of Islets Cell Hyperplasia Diagnosed by Selective Arterial Calcium Stimulation Test.: Jin Hoon Youn, Kyu Jeung Ahn, Yeong Shil Joo, Byoung Joon Kim, Sung Hoon Kim, Kye Hyoung Kwon, Myung Ah Jung, Jin Soo Yang, In Su Jung, Chung Hyeon Kim, Sung Bum Cho, Tae Seok Lee, Eun Kyung Kim; J Korean Endocr Soc. 2001;16(4-5):514-519. Published online October 1, 2001

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Abstract PDF: We report a 40-year-old female patient with clinical findings suggestive of insulinoma. Although imaging studies did not reveal any tumors in the pancreas, a selective arterial calcium stimulation test(SACI), procedurally simpler and more effective than transhepatic pancreatic venous sampling, was performed. And then near total pancreatectomy was carried out because the possibility of small insulinoma could not be completely excluded. Grossly, the surgically removed pancreas did not reveal any tumors. However, the pancreas exhibited islets cell hyperplasia. To our knowledge, this is the first reported authentic case in a Korean adult of islet-cell hyperplasia diagnosed by selective arterial calcium stimulation test.

Development of Tertiary Hyperparathyroidism during the Treatment of Hypophosphatemic Osteomalacia.: W S Shinn, S Lim, Y M Cho, T Y Kim, M K Moon, D J Park, K S Park, S Y Kim, B Y Cho, H K Lee, Y K Youn, S K Oh; J Korean Endocr Soc. 2001;16(4-5):520-527. Published online October 1, 2001

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Abstract PDF: Osteomalacia is characterized by the accumulation of an increased amount of unmineralized bone matrix. Of the several possible causes, hypophosphatemia is one of the major and mainly results from intestinal malabsorption of phosphate or from renal tubular phosphate loss. Oral phosphate supplementation is the mainstay of therapy for hypophosphatemic osteomalacia of diverse causes, but secondary hyperparathyroidism may be induced by such treatment. Although concomitant therapy with vitamin D is recommended for the prevention of this complication, it can nevertheless occur and sometimes results in tertiary hyperparathyroidism. We report the development of tertiary hyperparathyroidism in a patient with sporadic non-familial hypophosphatemic osteomalacia who had been treated with long-term phosphate therapy despite undergoing concomitant vitamin D therapy.

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