• Korean Journal of Head & Neck Oncology
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• v.15 no.2
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• pp.141-148
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• 1999

Objectives: The development of thyroid tumor has a relationship with carcinogen, oncogene and tumor suppressor gene. With aminotriazole, radioactive iodine and nitrosomethylurea as carcinogens in rat, authors investigate the incidence in type of the thyroid tumors, p21 and p53 protein expression pattern by immunohistochemical stain and the relationship between the tumors and p21-p53 protein expressions. Materials and Methods: 80 experimental animals were divided into four groups; group 1(control, no carcinogen, n=20), group 2(oral administration of aminotriazole for 36 weeks, n=20), group 3(intraperitoneal injection of 131I for one time and oral administration of aminotriazole for 36 weeks, n=20), group 4(oral administration of nitrosomethylurea for 3 days and aminotriazole for 36 weeks, n=20). After 40 weeks they were sacrificed with pathologic examination and we performed immunohistochemical staining with pan-ras monoclonal antibody for p21 protein and CMI polyclonal antibody for p53 protein with paraffin-embedded specimens. Results: 1) No tumors were observed in group I, but 38.3% of nodular goiters, 11.7% of adenomas and 50.0% of carcinomas were observed in carcinogen treated groups(group 2, 3, 4). 2) The incidence of nodular goiter, adenoma and carcinoma were 70%, 20% and 10% in group 2, 40%, 15% and 45% in group 3 and 5%, 0% and 95% in group 4. 3) p21 protein was not expressed in normal thyroid tissues but was expressed in 26.1% of nodular goiters, 42.9% of adenomas and 6.7% of carcinomas. On the other hands, p53 protein was not expressed in normal thyroid tissues, nodular goiters, adenomas and in well differentiated thyroid carcinomas by immunohistochemical stain. Conclusion: The authors suggest that aminotrizole, 131I, nitrosomethylurea can be etiologic agents in the development of thyroid tumor and the p21 protein can be expressed in the early stage and in benign condition of thyroid tumor but p53 protein is not expressed in all conditions of development in rats.

• The Korean Journal of Nuclear Medicine
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• v.4 no.1
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• pp.43-49
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• 1970

In recent years with development of immuno-electrophoresis, more acurate analysis of the serum protein became possible. However, there is few reports in the literature which investigated the changes of the immunoglobulin compared with electrophoretically fractioned serum thyroglobulin in the patients with various thyroid diseases. The purpose of this report is to investigate the changes of thyroglobulin in various thyroid diseases by the method of immuno-electrophoresis and to compare the results with.serum protein fractionated by the method of agar-gel micro-electrophoresis. Materials and Methods: Sera from 9 patients with diffuse toxic goiter, 2 nodular nontoxic goiter, 2 thyroiditis, 3 hypothy, roidism, 1 thyroid cancer, 7 cystic degeneration of the thyroid gland, and 10 normal subject were taken. All cases were confirmed by various laboratory thyroid function tests and thyroid needle biopsy. Immuno-electrophoretic analysis of the serum were performed by Scheidegger's modified micro-immuno-electrophoretic method. The antiserum was obtained from the Travenol Laboratories International, Hyland Products Division and was rabbit anti-human thyroglobulin. Microscope slide agar-gel electrophoresis for serum protein fractionation was performed at $4^{\circ}C$ using veronal buffer, pH 8.6 and ionic strength 0.05, with 54 volts and 2.8 mA for 60 minutes. The fractionated slide was stained with 0.1% thiazine red. The results were as follows: 1) Increase of immune-globulin macroglobulin (IgM), alphaglobulin, and immune-globulin A (IgA) by 95.8%, 100%, 29.2% respectively was found in the serum from various thyroid diseases. 2) Thyroglobulin fraction was found to be increased in 50%, no change in 41.7%, and no line in 8.3% with all of the various goiter patients. On the other hand, 10 normal control group showed only 2 cases of increase, 5 cases of no change and 3 cases of no line.

• The Korean Journal of Nuclear Medicine
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• v.20 no.1
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• pp.67-73
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• 1986

Subclinical hypothyroidism can be defined as an asymptomatic state in which a reduction in thyroid activity has been compensated by an increased TSH output to maintain a euthyroid state. We analysed clinical features, laboratory data, and pathologic findings in 3g cases of subclinical hypothyroidism who were diagnosed at the Dept. of Internal Medicine, Chungnam National University Hospital from Aug. 1984 to June, 1985. 1) The age distribution was from sixteen to sixty-nine and mean a9e was 34.8. Peak incidence was in the 4th decade and 3rd, 5th, 6th decade in order. 2) The sex distribution showed female preponderance with a ratio of 18.5 to 1. 3) The major presenting manifestations were nonspecific ones such as fatigue, indigestion, and anorexia. 4) Physical examination revealed diffuse goiter in 47.6%. Major abnormalities were no gross abnormality (30.9%), nodular goiter and facial edema. 5) There was no significant difference of the basal serum $T_3\;and\;T_4$ concentrations between subclinical hypothyroidism and normal controls (p>0.05). 6) The basal serum TSH concentration of subclinical hypothyroidism $(32.61{\pm}14.95{\mu}U/ml)$ was significantly higher than that of normal controls $(3.92{\pm}1.05{\mu}U/ml)$ (p<0.005). 7) Microsomal antibody was detected in 80.6% and thyroglobulin antibody was detected in 30%. 8) The pathologic findings in 26 cases revealed Hashimoto's thyroiditis in 76.9% (lymphocytic type, 34.6%; oxyphilic type, 26.9%; fibrotic type, 15.4%). The others were adenomatous goiter(15.4%), adenomatous carcinoma (3.8%) and subacute thyroiditis(3.8%).

• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.155-161
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• 2001

Background and Objectives: Nitric oxide (NO) is generated in mammalian tissue by the conversion of L-arginine to L-citrulline. This reaction is catalyzed by nitric oxide synthase (NOS). NO is an important bioactive agent and a signalling molecule that mediates a variety of biologic actions such as vasodilation, neurotransmission, host defense, and iron metabolism but increased NO production may also contribute to the pathogenesis of a various of disorders, including cancer. Before now, the role of NO in thyroid gland is still investigated and it was supposed that NO mediate the angiogenesis in tumor growth. Others journal and works identified the expression of iNOS that involve by neutrophil and eNOS that involve in part in the vascular remodeling and to understand the role of NO in human thyroid gland. But authors revealed only eNOS in thyroid neoplasm. iNOS was identifed by inflammation in fault. Materials and Methods: Western blot analysis was performed, using a polyclonal antibody against eNOS (Rabbit polyclonal IgG). Using the same antibody, the distribution of eNOS was examined in 15 formalin-fixed paraffin embedded samples by immunohistochemistry. By NADPH consumption rate, NOS activity was estimated at nodular hyperplasia. Results: Western blot analysis exhibited that eNOS was significantly elevated in thyroid papillary carcinoma, compared to that in nodular hyperplasia and normal tissue. Immunohistochemistry showed that the immunoreacitivity was present more significantly in thyroid follicular epithelial cell layer than vascular endothelial cell. NOS activity increased in nodular hyperplasia. Conclusions: Thyroid papillary cancer without neutrophil invasion expressed only eNOS. The endothelial localization of eNOS may play an important role in pathogenensis of human thyroid nodular hyperplasia and the follicular localization of thyroid papillary carcinomas.

• The Korean Journal of Nuclear Medicine
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• v.17 no.1
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• pp.17-23
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• 1983

In an attempt to evaluate the diagnostic singnificance of the serum thyroglobulin (TG) in various thyroid disease states, authors measured serum TG by radioimmunoassay technique in 20 cases of normal subject, 22 cases of hyperthyroidism, 12 cases of diffuse nontoxic goiter (DNG) and 96 cases of nodular nontoxic goiter(NNG). The results were as follows: 1. In 20 cases of normal subjects, serum TG level was $20.41{\pm}5.5ng/ml(M{\pm}S.D.)$. There was no significant difference between males ans females. 2. In 22 cases of hyperthyroidism, serum TG level was $60.23{\pm}34.56ng/ml$ and the range was from 22 to 175 ng/ml, which were significantly high levels comparing with normal controls (p<0.01). 3. In 12 cases of euthyroidism with DNG, serum TG was $37.28{\pm}27.36ng/ml$ and the range was from 14 to 89 ng/ml. In 96 cases of euthyroidism with NNG, serum TG was $70.43{\pm}78.18ng/ml$ and the range was from 12.8 to 440 ng/ml. Both groups showed significantly increased levels of TG than normal control (p<0.01). 4. 57 cases of NNG patients were analysed pathologically by operation or needle biopsy and the TG level of each disease group is as follows. Thyroid carcinoma (16 cases); $72.2{\pm}81.71ng/ml$, adenomatous goiter without cystic degeneration (15 cases); $74.86{\pm}45.64ng/ml(M{\pm}S.D.)$ and adenomatous goiter with cystic degeneration(23 cases); $73.56{\pm}64.78ng/ml(M{\pm}S.D.)$. There was no significant difference between each group. Also the TG levels of thyroiditis (5 cases) was $19.6{\pm}8.96ng/ml(M{\pm}S.D.)$. 5. There were no significant correlations between serum thyroid hormones and serum TG in each thyroid functional states.

• The Korean Journal of Cytopathology
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• v.11 no.2
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• pp.109-114
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• 2000

Amyloid golfer is a rare disease entity that is defined as a symptomatic mass or clinically detectable thyroid enlargement because of amyloid deposition. We present a case of amyloid golfer diagnosed in the fine needle aspiration cytology(FNAC) in a 73-year-old Korean woman presented with nephrotic syndrome and thyroid enlargement. The thyroid function was in normal range. Thyroid scan showed a nodule, $4{\time}2cm$ in the right lobe with underlying diffuse golfer. Aspirates revealed benign looking follicular cells and scattered eosinophilic material. The sections of the cell block showed nodular deposit of eosinophilic hyalinized material in the interfollicular area. It showed apple-green birefringence under polarization with Congo red stain. The renal biopsy also exhibited deposition of eosinophilic materials in the glomeruli and interstitial vascular wall, which were confirmed as amyloidosis. This material was morphologically distinct from the colloid.

• Korean Journal of Head & Neck Oncology
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• v.14 no.1
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• pp.88-93
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• 1998

In order to review the clinicopathologic characteristics of the thyroid cancer associated with benign thyroid disease, we evaluated 47 patients treated between January, 1993 and September, 1997 at the Chonnam National University Hospital. In those period, we had operated a total of 690 thyroidectomy of which 320 were diagnosed as thyroid cancer. Forty three(91.4%)occurred in women and four(8.5%)occurred in men. The mean age at operation was 46.7years(range, 15 to 76 years). Forty three of the 47 cancers(91.4%) were papillary carcinomas while 4(8.5%)were follicular. Twenty four of the 47 patients (51%) were occult thyroid carcinomas measured less than 1 cm in diameter. The concurrent benign disease were nodular goiter(n=17), Hashimoto's thyroiditis(n=16), follicular adenoma(n=10), Graves' disease(n=2) and diffuse hyperplasia(n=2). Thirty one patients were diagnosed by preoperative FNAC and they underwent total thyroidectomy. Three were diagnosed by frozen section examination at the time of operation. Among them, one underwent total thyroidectomy and two underwent subtotal thyroidectomy. Eight cases revealed lymph node metastases and 2 cases extended to surrounding muscles. In conclusion, concurrent thyroid cancers and benign thyroid disease are not uncommon and a regular ultrasonic follow-up with selective aspiration cytologic examination is recommaned to enhance their diagnostic accuracy.

• The Korean Journal of Nuclear Medicine
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• v.20 no.1
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• pp.53-58
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• 1986

Thyroid scans using $Na^{131}I\;and\;^{99m}TcO_4^-$ in two (anterior and anterior oblique) projections were done simultaneously in 50 patients with single palpable nodule and in euthyroid state(nodular nontoxic goiter) and 20 normal subjects to evaluate the imaging ability of each radionuclide and the necessity of oblique view. In detection of a nodule as a cold or cool area, $^{99m}TcO_4^-$ was slightly superior to $^{131}I$(82 % to 78% with anterior view alone, 92% to 84% when oblique view is added in detectability), with addition of an oblique view, 5 more cold or cool area in $^{99m}Tc$ scan and 3 more $^{131}I$ scan were detected. In normal subjects $^{99m}TcO_4^-$ scan was significantly superior to $^{131}I$ scan(90% to 70%) in getting normal pattern of tracer uptake in the glands. For routine imaging study of the thyroid, $^{99m}Tc$ pertechnetate scan with multiple projection is considered to be a preferable method.

• Korean Journal of Head & Neck Oncology
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• v.27 no.2
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• pp.198-203
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• 2011

Background and Objectives : Distinguishing benign from malignant lesion in thyroid noddex is important but clinically difficult. FNAB is the first investigation of choice. However, cytologic results are often indeterminable. In those cases, additional molecular biologic tests are helpful. If serologic tests are available to predict malignancy, it can be useful to fortify accurate diagnosis. We analyzed whether TSH or FreeT4 level could be used as a predictor of malignancy. Materials and Methods : From January 2008 to March 2009, 540 patients received one of thyroidectomy in a single center. We only included 167 patients from 18 to 65 years old without cardiopulmonary or renal disorders. All the patients were in euthyroid state and took no medications, which affect the thyroid function. We reviewed charts retrospectively to find out differences in TSH level and FreeT4 level between the benign and malignant groups. Results : In this study, all the patients with malignancy had the papillary cancer. In benign group, average TSH level came out to be 1.48mU/L, whereas the average TSH level of malignant group was 1.98 mU/L. Moreover, the higher the cancer stage was, the higher the TSH level was. Although we have adjusted factors that can affect TSH level(age, sex, race, goiter type), we still received the same result. The risk of malignant cancer increased in proportion with TSH level within the normal range. In free T4 level, there was no difference between benign and malignant group. Conclusion : We propose that TSH level can play a role as one of the predictors for thyroid cancer. However, there is limitation because all the patients with malignancy in this study have papillary cancer. Thus, we can apply this result only in papillary cancer, and we need more study for other types of thyroid cancer.

• Korean Journal of Otorhinolaryngology-Head and Neck Surgery
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• v.61 no.11
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• pp.600-604
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• 2018

Background and Objectives This study aimed to identify a reliable preoperative predictive factor for the development of thyroid cancer in patients with atypia of undetermined significance (AUS) identified by fine needle aspiration biopsy (FNAB). Subjects and Method This was a retrospective cohort study. Two hundred and ninety-nine patients diagnosed with AUS by preoperative FNAB who underwent curative thyroid surgery at our institution between September 2005 and February 2014 were analyzed. Clinical, radiological and molecular features were investigated as preoperative predictors for postoperative permanent malignant pathology. Results The final pathologic results revealed 36 benign tumors including nodular hyperplasia, follicular adenoma, adenomatous goiter, nontoxic goiter, and lymphocytic thyroiditis, as well as 263 malignant tumors including 1 follicular carcinoma and 1 invasive follicular carcinoma; the rest were papillary thyroid carcinomas. The malignancy rate was 87.9%. The following were identified as risk factors for malignancy by univariate analysis: $BRAF^{V600E}$ gene mutation, specific ultrasonographic findings including smaller nodule size, low echogenicity of the nodule, and irregular or spiculated margin (p<0.05). Multivariate analysis revealed that only $BRAF^{V600E}$ mutation was a statistically significant risk factor for malignancy (p<0.05). When $BRAF^{V600E}$ mutation was positive, 98.5% of enrolled patients developed malignant tumors. In addition, the diagnostic rate of malignancy in these cases was approximately 16-fold higher than BRAF-negative cases. Conclusion Patients with AUS thyroid nodules should undergo $BRAF^{V600E}$ gene mutation analysis to improve diagnostic accuracy and if the mutation is confirmed, surgery is recommended due to the high risk of malignancy.