Endocrinology and Metabolism

Volume 18(2); April 2003

Review Articles

Metabolic Syndrome.: Min Kyong Moon, Young Min Cho, Soo Lim, Kyong Soo Park, Hong Kyu Lee; J Korean Endocr Soc. 2003;18(2):105-119. Published online April 1, 2003

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Abstract PDF: No abstract available.

Specialized Functions and Hormonal Regulation of Sertoli Cell.: Kyu Lim, Chung Park, Kyung Ah Yun, Eun Jin Yun, Jong Il Park, Seung Kiel Park, Byung Doo Hwang; J Korean Endocr Soc. 2003;18(2):120-136. Published online April 1, 2003

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Abstract PDF: No abstract available.

Leptin and Bone Metabolism.: Chan Soo Shin; J Korean Endocr Soc. 2003;18(2):137-139. Published online April 1, 2003

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Abstract PDF: No abstract available.

Original Articles

Expression of RET in Thyroid Diseases of a Korean Population.: Si Hoon Lee, Soon Won Hong, Woo Chul Moon, Myoung Ryur Oh, Jin Kyung Lee, Bong Soo Cha, Chul Woo Ahn, Kyung Rae Kim, Sung Kil Lim, Hyun Chul Lee; J Korean Endocr Soc. 2003;18(2):140-152. Published online April 1, 2003

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Abstract PDF: BACKGROUND
Activation of the RET proto-oncogene, located on the long arms of chromosome 10, contributes to the development of thyroid cancers in two different ways. Somatic rearrangements of RET with variable genes of activation are frequently found in papillary thyroid carcinomas. And Ggerm-line point mutations are responsible for the development of medullary thyroid carcinoma and the multiple endocrine neoplasia type 2(MEN2). There are several conflicting reports on the influences of RET expression and RET/PTC rearrangements on the clinical outcome of thyroid cancer. Therefore, we performed an examination of RET expression and RET/PTC-1, -2, -3 rearrangements in papillary thyroid carcinomas and other thyroid diseases. METHODS: Twenty-six papillary thyroid carcinomas(PTCs), three follicular thyroid carcinomas (FTCs), one anaplastic thyroid carcinoma(ATC), five follicular adenomas(FAs), nineteen hyperplasias, and two normal thyroid tissues were included in this study. RT-PCR and immunohistochemistry analysis were done to identify RET gene, RET/PTC rearrangements, and ret RET protein expression. RESULTS: By RT-PCR, 89.4% of PTCs, 100% of FTCs, and 62.1% of hyperplasias expressed the RET gene, but no RET was observed in ATCs, FAs, and normal thyroid tissues. RET/PTC-1, -2,-3 rearrangements were not detected in any specimens. Immunohistochemical results revealed that 76.9% of PTCs, 50% of FAs, 52.3% of hyperplasias, and 20.6% of normal thyroid tissues expressed the RET ret protein, but FTCs and ATCs did not. Most PTCs showed strong cytoplasmic positivity in RET ret immunostaining, but the positive non- PTCs expressed weak and membranous staining. Overall, the two methods for detecting RET gene, RT-PCR and immunohistochemistry showed similar results. CONCLUSION: The RET gene was highly expressed in PTCs. In contrast to the previous reports of that theRET gene expression of RET gene is being limited to PTCs, RET was also expressed in hyperplasias, Fas, and normal thyroid tissues. However, the pattern and the degree of expression of the RET ret protein in non- PTCs were are different from those in PTCs.

Serum Thyroglobulin Levels Predicting Recurrence and Distant Metastasis after Surgery in Patients with Differentiated Thyroid Cancer.: Kyoung Soo Kim, Jin Sook Ryu, Suck Joon Hong, Won Bae Kim, Young Kee Shong; J Korean Endocr Soc. 2003;18(2):153-165. Published online April 1, 2003

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Abstract PDF: BACKGROUND
Reports on serum thyroglobulin(Tg) levels being used to predict recurrence or distant metastasis during the follow-up of patients with differentiated thyroid cancer(DTC) has been inconsistent. In addition, there have been few reports that attempt to define the cut-off value of Tg for recurrence or distant metastasis obtained by a receiver operating characteristic(ROC) curve. As well, there are differences in opinions on what the value should be on the first serum Tg level measured just before radioactive iodine(RAI) ablation(Tg-RAI), during thyroxine administration (Tg-on), and after thyroxine withdrawal(Tg-off) during the follow-up. Reports on the positive predictive values(PPVs) and negative predictive values(NPVs) of these Tg values are rare. METHODS: A total of 205 patients(42 males, 163 females) with DTC were studied. All patients had undergone total or near-total thyroidectomy. After surgery and RAI ablation, annual thyroxine withdrawal 131I-whole body scan(WBS) with Tg measurements was performed. The mean duration of follow-up was 5.0 (1.4~7.4) years. The most sensitive and specific Tg values(cut-off values) for tumor recurrence and/or distant metastasis were selected by using ROC curves. We also calculated the PPVs and NPVs for recurrence and/or distant metastasis using two-by-two tables. RESULTS: Cut-off values of Tg-RAI, Tg-on, and Tg-off for recurrence were 11.8, 1.4, and 3.3ng/mL, respectively. For these values, the sensitivities were 85.4, 82.2, and 93.3%, with the specificitiesat 89.2, 92.4, and 88.0%. PPVs were 71.9, 77.1, and 77.0% while NPVs were 95.0, 94,4, and 97.8%. The cut-off values for distant metastasis were 27.4, 2.5, and 7.9ng/mL, respectively. For these cut-off values, the sensitivities were 86.7, 87.5, and 92.3%, with the specificities being 86.2, 90.8, and 80.2%. PPVs were 34.2, 46.7, and 25.0% and NPVs were 98.7, 98.8, and 99.3%. CONCLUSION: All three serum Tg levels were sensitive and specific markers for recurrence and distant metastasis. Their PPVs were low in contrast to the high NPVs. In comparison with Tg-on, Tg-off showed higher sensitivity and NPV as well as lower specificity and PPV. Therefore, in the case of higher Tg-on during the follow-up period, efforts to find recurrence and distant metastasis,such as 131I-WBS, should be done. In addition, regular measurement of Tg-off or Tg after stimulation with recombinant human TSH is recommended as a screening test.

Effect of LiCl on Iodine Kinetics in Thyroid Cancer Cell Lines Transduced by Recombinant Adenovirus Containing Sodium Iodide Symporter(NIS) Gene.: Won Bae Kim, Ja Young Song, Sung Min Han, Jeong Seok Yeo, Heui ran Lee, Young Kee Shong, Dae Hyuk Moon; J Korean Endocr Soc. 2003;18(2):166-176. Published online April 1, 2003

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Abstract PDF: BACKGROUND
Lithium is known to increase the retention of iodide in the thyroid gland, or in well differentiated thyroid cancer tissue. The effects of lithium on the function of the sodium iodide symporter (NIS) protein, especially when the lithium is increased in the retention of iodide in NIS-producing cells, the effect of lithium, on the kinetics of undifferentiated thyroid cancer cells transduced by a recombinant adenovirus containing the NIS gene, were checked. METHOD: Human NIS cDNA was inserted into pAxCAwt, a recombinant adenoviral cosmid vector, where the E1 & E2 genes have been deleted, making Rad-hNIS, which was propagated in 293 cells. The iodide uptake was evaluated by the 125I uptake assay in the undifferentiated thyroid cancer cells, ARO, FRO and NPA, following the infection with Rad-hNIS (1 or 10 MOI) in the presence, or absence, of LiCl at optimized concentrations. The iodide efflux was evaluated by the 125I efflux assay, for 1 hour, in the same cells expressing the NIS in the presence, or absence, of LiCl. Similar experiments were performed in the normal thyroid cell line, FRTL-5, cultured in 6H5 media. RESULTS: LiCl, at concentrations over 1.0mM, caused a significant decrease in the cell viability, as evaluated by trypan blue dye exclusion, in a dose dependent manner. When infected with Rad-hNIS, the iodide uptake was not affected by the LiCl in the ARO or NPA cells. However, LiCl(0.1and 1.0mM) increased the iodide uptake by 50 to 100%(vs. control) in the Rad-hNIS transduced FRO cells. In the Rad-hNIS transduced FRO cells, the iodide was released rapidly from the cells, with only 20.7+/-4.8% of the iodide uptake remaining at 1 hour, which was no different in the presence of LiCl (24.5+/-7.9%). The iodide efflux was not affected by the LiCl in the FRTL-5 cells cultured in the presence of TSH. CONCLUSION: These results suggest that the lithium-induced iodide retention in the thyroid gland, or in well differentiated thyroid cancer tissue, is not caused by the effect of the lithium on the NIS function, or the function of proteins or channels, involved in iodide transport via cell membranes. Although the iodide uptake can be markedly increased by the expression of NIS, with the transduction of Rad-hNIS, in undifferentiated thyroid cancer cells, the iodide taken up is rapidly released from the cells. A method for inducing the iodide retention in the cell should be elucidated in order to render the NIS gene therapy effective.

Association between Serum Leptin Concentration and Bone Mineral Density in Healthy Korean Women.: Yumie Rhee, Dae Jung Kim, Se Hwa Kim, Chul Woo Ahn, Bong Soo Cha, Kyung Rae Kim, Hyun Chul Lee, Sung Kil Lim; J Korean Endocr Soc. 2003;18(2):177-183. Published online April 1, 2003

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Abstract PDF: BACKGROUND
Leptin is known to affect bone metabolism both centrally and peripherally. This study was performed to investigate the relationship between leptin and bone mineral density(BMD) in healthy premenopausal and postmenopausal Korean women. METHODS: 140 women were recruited for a routine health check-up. Anthro-pometric and biochemical data were checked as usual. BMDs were measured by dual x-ray absorptiometry of the spine and femur in 67 premenopausal women and 73 postmenopausal women, in addition to their serum leptin levels. RESULTS: Serum leptin level showed no correlation with BMD in premenopausal women, but there was a positive correlation betwen serum leptin and spinal BMD in postmenopausal women(r=0.468, p<0.001). After the correcting for age, body mass index, and duration of menopause, the serum leptin level and BMD still showed a positive correlation(r=0.217, p=0.088) although weak. The women in the lowest quartile of serum leptin level showed significantly lower lumbar and femoral neck BMD. CONCLUSION: Leptin level seems to have a weak relationship with BMD showing different features in premenopausal and postmenopausal women.

Association of Polymorphism in beta3-Adrenergic Receptor Gene with Fat Distribution.: Tae Sung Yun, Yong Deuk Kim, Hye Soon Kim, Mi Jung Kim, Young Sung Suh, Jung Hyeok Kwon, Jin Soo Choi, Jung Guk Kim, Sung Woo Ha, Bo Wan Kim, Kyu Chang Won, Hyong Woo Lee, Ho Sang Shon, Ji Hyun Lee, Hyun Dae Yoon, Won Ho Kim, Young Gil Yun, In Kyu Lee; J Korean Endocr Soc. 2003;18(2):184-192. Published online April 1, 2003

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Abstract PDF: BACKGROUND
Reasons for obesity include environmental factors and, more largely so, genetic factors. There have been many studies on these genetic factors. So far, genes related to obesity such as Leptin, Uncoupling Protein(UCP), Peroxisome proliferator activated receptor-gamma(PPAR-gamma), and Beta3-adrener-gic receptor(beta3-AR) gene have been discovered. Among these, beta3-AR is expressed in visceral adipose tissue and is thought to contribute to the regulation of resting metabolic rate and lipolysis. The missense mutation of beta3-AR gene, resulting in replacement of tryptophan by arginine at position 64(Trp64Arg), is associated with decreased resting metabolic rate and weightgain. We performed this study to determine if Trp64Arg polymorphism of beta3-AR gene is associatedwith obesity in Koreans. METHOD: We investigated the relationship between the beta3-AR gene mutation and body mass index (BMI), waist circumference, hip circumference, waist to hip ratio(WHR), area of subcutaneous fat, area of visceral fat, visceral to subcutaneous fat ratio(VSR), and lipid profile. 198 subjects were included in this study of which 97 were of normal weight and 101 were obese. Anthropometric data was obtained from physical examination and medical records. RESULT: In the cases of beta3-AR gene mutation of the obese group, the ratio of Trp/Arg and Arg/Arg are 43% and 5%, respectively, which were higher than the normal group(36%, 1%), although a statistical significant was not found. There was significant difference in the are of subcutaneous fat. Normal group(Trp/Trp) measured at 213.9+/-109.6cm2 versus 244.0+/-127.7cm2 (Trp/Arg) and 323.9+/-189.9cm2(Arg/Arg) for the mutation groups. Circumference of waist, circumference of hip, WHR, area of visceral fat, and VSR were higher in the mutation groups than in normal subject, but not significantly different. CONCLUSION: These results suggest that a genetic mutation in the beta3-AR gene can affect body fat composition, and is associated with obesity in Korean adults.

Determinants of Limb-Bone Mineral Density in Healthy Men and Women Aged over 50 in Rural Area.: Soo Lim, Chan Soo Shin, Ki Sook Kim, Soo Youn Kim, Eun Joo Bang, Eun Kyung Shin, Hye Ran Choi, Moon Ho Chung, Sung Il Cho; J Korean Endocr Soc. 2003;18(2):193-205. Published online April 1, 2003

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Abstract PDF: BACKGROUND
Many studies have shown a strong inverse relationship between the bone mineral density (BMD) and osteoporotic fractures, with a doubling in the incidence of fractures for each standard deviation reduction in the BMD. Newer peripheral densitometry devices have recently been developed, with the advantages of a low cost and increased portability. In addition, studies focusing on the osteoporosis of rural populations are rare. The authors assessed the factors related with the BMD in rural areas, using peripheral bone densitometry. METHODS: 23 men (68.4+/-9.2[mean age+/-SD] years) and 32 women (63.9+/-8.3 years), living in rural areas, voluntarily participated in this community-based study. The BMD of the distal radius (BMDr) and calcaneus (BMDc) were measured using peripheral dual-energy X-ray absorptiometry. The BMI, waist to hip ratio, body composition, blood pressure, lipids, fasting glucose and insulin were measured. The sociodemographic characteristics and physical activities were investigated using questionnaires. RESULTS: 21.7% of the men and 34.4% of the women were diagnosed with osteoporosis according to the WHO definition. The BMDr and BMDc were 0.46+/-0.08 and 0.46+/-0.11 and 0.34+/-0.07 and 0.33+/-0.08g/cm2 in the men and women, respectively. In the men, age, BMI, physical activity and smoking were correlated with the BMDr, and age, lean body mass, physical activity, TV watching and smoking with the BMDc. In the women, age, weight and lean body mass were correlated with the BMDr, and age, weight, BMI, waist circumference, fat mass, lean body mass and year since menopause with the BMDc. From a multiple regression analysis, age and smoking in men, and year since menopause and lean body mass in women, respectively, had independent effects on the BMD. CONCLUSION: In the rural community studied, osteoporosis was as highly prevalent as in urban communities. Of the determinants for the BMD, smoking for men, and lean body mass for women, were modifiable factors. Education for quitting smoking in men, and maintenance of optimal weight in women, are required to prevent osteoporosis in rural areas.

Case Reports

A Case of Syndrome of Resistance to Thyroid Hormone Associated with Mutation(M313T) in Thyroid Hormone Receptor Beta Gene.: Jae Kyung Hwang, Kyung Won Kim, Tae Yong Kim, Sang Wan Kim, Young Joo Park, Do Joon Park, Seong Yeon Kim, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2003;18(2):206-213. Published online April 1, 2003

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Abstract PDF: Syndrome of resistance to thyroid hormone(RTH) is inherited by an autosomal dominant trait, and characterized by elevated thyroid hormone levels with reduced responsiveness of the pituitary and peripheral tissues to thyroid hormone action. All of the reported RTH patients have various mutations in the ligand-binding domain coding region of the thyroid hormone receptor beta gene. A 21-year-old man visited our hospital complaining of fatigue. He had mild thyroid goiter and intermittent palpitation. Thyroid function test showed elevated total T3, free T4, and TSH levels. Levels of TSH free a-subunit and basal pituitary hormones, except prolactin, were normal. MRI of the sellar region showed no abnormal finding. TSH response to TRH stimulation was normal, and TSH values to TRH stimulation after T3 suppression revealed partial response. Sequeuce analysis of the thyroid hormone receptor beta gene confirmed a heterozygous missense mutation in exon 9; and the amino acid alteration was a substitution of a threonine(ACG) for a methionine(ATG) at codon313. Sequeuce analysis of the parents showed no mutation.We report the first case of a man with RTH caused by a de novo mutation(M313T) in TRbeta gene, confirmed by sequeuce analysis.

A Case of Cystic Parathyroid Adenoma Presenting as Severe Bony Lesion.: Suk Chon, Young Hee Kim, Ji Young Park, Kwan Pyo Ko, Cheol Young Park, Deog Yoon Kim, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Suck Hwan Go; J Korean Endocr Soc. 2003;18(2):214-220. Published online April 1, 2003

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Abstract PDF: A cystic parathyroid adenoma is rare. A case of primary hyperparathyroidism, with the cystic formation of a parathyroid adenoma and a severe bony lesion, is reported. A 52-year-old male was admitted due to pain in both hips and for evaluation of hypercalcemia. The plasma level of the intact parathyroid hormone(iPTH) was elevated to 1424pg/mL. Ultrasonography and the computed tomography revealed a parathyroid cyst on the left thyroid lower pole. Parathyroid scintigraphy detected a parathyroid adenoma. A radiograph showed a subperiosteal bone resorption on the phalanges, and a brown tumor(osteitis fibrosa cystica) on the femur shaft was noted. A surgical excision of the parathyroid adenoma was performed. The PTH level in the cystic fluid was increased. A histological examination confirmed a cystic parathyroid adenoma. The PTH level was normalized after the operation.

A Case of Brown Tumor with Severe Hypercalcemia Caused by Parathyroid Adenoma.: Ji Oh Mok; J Korean Endocr Soc. 2003;18(2):221-226. Published online April 1, 2003

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Abstract PDF: Most of primary hyperparathyroidism results from parathyroid adenoma, and is characterized by hypercalcemia, reduced bone density, frequent renal stone, gastric ulcer, duodenal ulcer, muscle weakness, depression, hypertension, anemia, and rarely brown tumor. We had a case of an 80-year-old man having brown tumor caused by primary hyperparathyroidism on the right 10th rib confirmed by CT guided bone biopsy. The patient presented with decreased level of consciousness, acute gastric ulcer, acute duodenal ulcer, GB stones, renal insufficiency, depression, and osteoporosis. Serum calcium level was 16.7 mg/dL and the intact parathyroid hormone level was 3901pg/mL. A parathyroid mass was detected by neck CT and 99mTc-tetrofosmin parathyroid scan. The parathyroid tumor was removed and confirmed as a parathyroid adenoma by pathology. After operation, the patient was treated with vitamin D and calcium in response to the resulting hungry bone syndrome. The intact PTH level returned to a normal range after the removal of the parathyroid adenoma.

A Case of Pheochromocytoma with Ganglioneuronal Differentiation Producing Vasoactive Intestinal Peptide.: Min Ah Na, Sang Soo Kim, Dong Uk Kim, Jae Hoon Choi, Tae Kun Lee, Ok Nyu Kong, Jun Hyeop An, Jee Yeon Kim, Han Dong Sung, Chul Ho Joung, Seok Man Son, In Joo Kim, Yong Ki Kim; J Korean Endocr Soc. 2003;18(2):227-231. Published online April 1, 2003

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Abstract PDF: Vasoactive intestinal peptide(VIP) is a 28-amino acid peptide, which may cause secretory diarrhea by stimulating the production of adenylate cyclase. Neuroendocrine tumors, secreting vasoactive intestinal peptide (VIP), are almost always of a pancreatic in origin. However, a pheochromocytoma may produce several neuropeptides, containing VIP, as they are considered to be neuroendocrine tumors. A 57-year-old woman, who presented with chronic watery diarrhea, hypokalemia, weight loss and a left adrenal mass, is described. Histologically, the tumor was diagnosed as a pheoch-romocytoma, with ganglioneuronal differentiation, and was histochemically confirmed to produce a vasoactive intestinal polypeptide. A left adrenal VIP-producing pheochromocytoma was successfully resected. After surgery, her diarrhea subsided and the electrolytes, affected neuroendocrine hormone levels, blood pressure and blood sugar level were normalized.

A Case of Adrenal Cortical Carcinoma with Liver Metastasis.: Hyun Joo Lee, Myung Soo Kim, Hyo Kyoung Park, Dae Jung Kim, Yu Mie Rhee, Chul Woo Ahn, Jae Hyun Nam, Bong Soo Cha, Young Duk Song, Sang Won Han, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; J Korean Endocr Soc. 2003;18(2):232-238. Published online April 1, 2003

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Abstract PDF: An adrenal cortical carcinoma is a rare malignancy associated with poor prognosis. On diagnosis, most patients present with large tumor masses, which are often detected at an advanced stage. The most effective treatment is a complete resection, which is the only curative treatment for adrenal cortical carcinomas. The most important prognostic factor is a successful resection of the primary tumor, as long as it is low-grade and has not spread to distant sites. However, with advanced adrenal cortical carcinomas, with distant metastasis, there is no strict effective treatment program, and the prognosis is poor. The case of a 50-year-old female patient, presenting with an adrenal cortical carcinoma and Cushing's syndrome, who had a long-term survival of 78 months, is reported. The mass was completely resected on diagnosis, but 16 months later liver metastasis was discovered. She had received chemotherapy, with cisplatin, etoposide and bleomycin, for the liver metastasis for a period of 15 months, but with no response, furthermore, the size had increased after 10 months. Afterward, she received her 10th session of intrahepatic artery cisplatin chemotherapy and her 3rd hepatic artery embolization. Although the patient had a large degree of liver metastasis, this was tolerated. The tumor mass is presently not aggravated, and she still survives after 78 months.

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