- Percutaneous Ethanol Injection in Autonomous Functioning Thyroid Nodules and Complex Cysts: Five Years' Experience.
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Seong Jin Lee, Jung Hee Han, Ha Young Kim, Jong Chul Won, Sang Wook Kim, Ho Kyu Lee, Il Min Ahn
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J Korean Endocr Soc. 2002;17(1):57-68. Published online February 1, 2002
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- 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
- Clinical Applications of 18-FDG PET in Recurred Differentiated Thyroid Cancer with Negative 131I Whole Body Scintigraphy: A Comparative Analysis with 99mTc-MIBI Scintigraphy.
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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
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J Korean Endocr Soc. 2001;16(4-5):481-493. Published online October 1, 2001
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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.
- A Case of Hashimotos Thyroiditis with Anti-Triiodothyronine Autoantibody.
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Yun Ey Chung, Jeong Hee Han, Seong Jin Lee, Won Ki Min, Ki Young Park, Kun Ku Park, Dae Hyunk Moon, Il Min Ahn
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J Korean Endocr Soc. 2001;16(2):245-251. Published online April 1, 2001
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- Autoantibodies against thyroid hormones can be detected in the sera of patients with both thyroidal and non-thyroidal disorders. These antibodies interfere with the radioimmunoassay of serum total and free thyroid hormone concentrations, resulting in a discrepancy between the measured hormone levels and clinical features. This can in turn lead to an erroneous diagnosis and patients may receive unnecessary treatment from physicians who are unaware of the presence of the autoantibodies. We experienced a woman having Hashimotos' thyroiditis with a spurious elevation of total T3 and free T3 values according to one-step analog-tracer radioimmunoassay who was had been treated as Graves' disease in past. Through the use of a polyethylene glycol precipitation method, she was subsequently revealed to have anti-triiodothyronine autoantibodies. We report this case with a review of related literature.
- Effectiveness of Percutaneous Ethanol Injection in Benign Cold Thyroid Nodules: Five Years' Experience.
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Seong Jin Lee, Jung Hee Han, Ha Young Kim, Jong Chul Won, Sang Wook Kim, Ho Kyu Lee, Il Min Ahn
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J Korean Endocr Soc. 2001;16(2):210-220. Published online April 1, 2001
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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.
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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
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J Korean Endocr Soc. 2001;16(1):75-84. Published online February 1, 2001
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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.
- Lanreotide Therapy in Graves' Ophthalmopathy.
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Il Seong Nam-Goong, Eun Ju Lee, Jung Hwoon Kim, Jong Chul Won, Woo jae Lee, Jung Hee Han, sung Jin Lee, Sang Wook Kim, Moo Kon Son, Ho Hye Lee, Il Min Ahn
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J Korean Endocr Soc. 2001;16(1):18-25. Published online February 1, 2001
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Graves' ophthalmopathy (GO) is an autoimmune process that affects the orbital tissues. Patients with GO are usually treated with high doses of corticosteroids, retrobulbar irradiation, or by surgical decompression, however, those have some adverse effect. Recently, a synthetic somatostatin analogue has been reported for the treatment of GO. This study was performed prospectively to evaluate the therapeutic effects of lanreotide, a potent long acting synthetic somatostatin analogue, in patients that have GO. METHODS: Eight patients with moderate to severe GO (M:F=1:7, age 39.0+/-11.8 years) were included. Patients who had been treated with other modalities than GO, or had a systemic illness such as diabetes were excluded. Eight patients were given lanreotide, 40mg IM every 2 weeks over a period of 8 weeks. Their therapeutic responses were evaluated using an orbital CT or MRI and by ophthalmologic examinations. RESULTS: After 8 weeks' of lanreotide treatment, 4 patients showed decreased scores in the NOSPECS classification (p=0.059) as well as 5 patients in their clinical activity scores(p=0.109). All of the 8 patients showed improvements according to clinical evaluation criteria (p=0.008). Significant changes in the thickness of both the lateral rectus and superior rectus muscles were observed (p<0.05). No patient showed serious adverse effects related to lanreotide therapy during the follow-up periods. CONCLUSION: We conclude that lanreotide therapy has clinical benefits and show radiologic improvements in GO. Considering the minimal side-effects of lanreotide compared to those of corticosteroid, lanreotide therapy should be considered for use in selected patients that have Graves' ophthalmopathy
- The Role of Preoperative and Postoperative Thyroglobulin Measurements in The Detection of Well Differentiated Thyroid Carcinomas Recurrence.
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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
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J Korean Endocr Soc. 2000;15(4-5):542-553. Published online January 1, 2001
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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.
- Enhanced Effect of Iodide - Uptake in Thyroid Carcinoma Cells by Infecting Adenovirus - Human Sodium Iodide Symporter (Ad - hNIS).
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Kun Koo Park, Jung Sun Jin, Seong Jin Lee, Jung Yoon Park, Heui Ran Lee, Dae Hyuk Moon, Il Min Ahn, Hye Sook Chang
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J Korean Endocr Soc. 2000;15(4-5):522-531. Published online January 1, 2001
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The sodium-iodide-symporter (NIS) is a plasma membrane glycoprotein with 13 putative transmembrane domains, which is responsible for concentrating iodide into the thyroid by an active transport and provides the mechanism for radioactive-iodine (RAI) therapy for thyroid cancer. However, undifferentiated thyroid cancers and about 2050% of differentiated thyroid cancers do not take up the RAI at therapeutic dose. The NIS has been cloned from rat and human (hNIS) and characterized recently. In an attempt to develop a new therapeutic strategy using hNIS gene for improving the efficacy of RAI therapy in thyroid cancers, we have constructed a recombinant adenovirus encoding the hNIS (Ad-hNIS) and tested its function by an iodide uptake by infecting human thyroid cancer cells. METHODS: RT-PCR was performed to measure an intrinsic hNIS expression in thyroid cancer cell lines, such as NPA, FRO and ARO. To generate the hNIS adenovirus, hNIS cDNA was isolated and ligated into Swa I site of cosmid shuttle vector (pAxCAwt). We have produced recombinant adenovirus by co-transfecting the cosmid with DNA-TPC to 293 cell line. Adenovirus that express (beta-Galactosidase (LacZ) was also prepared by the similar strategy. Adenovirus infection efficiency was measured in three thyroid cancer cell lines. Finally, 24 hours after infection of ad-hNIS into the cells, I125-uptake was measured. RESULTS: Endogenous hNIS expression was detected only in FRO cells but not in NPA, ARO and Hela cells by RT-PCR. X-Gal staining after infection of Ad-LacZ to thyroid cancer cell (NPA, ARO, FRO) showed that an infection rate in ARO cells was 98.5+0.5%, 97.0+0.2% in FRO cells and 75.5+5.0% in NPA cells. We selected ARO cells for the infection of Ad-hNIS due to the highest infection efficiency and the absence of endogenous hNIS expression. When ARO cells were infected with the ad-hNIS, I125 uptake was increased 504+6.4%. CONCLUSION: Overexpression of hNIS gene in thyroid cancer cells elicited over 5 fold increase in I-uptake, suggesting that the Ad-hNIS infection to the thyroid cancer cells may improve the efficiency of radioactive iodine therapy.
- FDG-PET as a Predictor of Recurrence with 131I Scan Negative Differentiated Thyroid Cancer: An Evaluation Compared with Pathologic Findings.
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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
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J Korean Endocr Soc. 1999;14(3):520-530. Published online January 1, 2001
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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.
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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
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J Korean Endocr Soc. 1999;14(3):514-519. Published online January 1, 2001
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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.
- Allelotyping and Comparative Genomin Hybridization Studies in Papillary Thyroid Carcinomas and Follicular Adenomas.
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Il Min Ahn, Eun Sook Kim, Hyun Soo Park, Ki Young Park, Seok Jun Hong, Kyung Yub Gong, Jin Yub Kim, Sung Bae Kim, Sang Hee Kim, Sung Jin Lee, Jung Hee Han, Kwan Ja Jee
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J Korean Endocr Soc. 1999;14(2):314-322. Published online January 1, 2001
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In our previous study, the prevalence of the known causes of thyroid tumorigenesis was relatively rare in Korean population, suggesting genetic and environmental differences exist. Screening of genetic alteration in papillary thyroid carcinoma(PTC) and follicular adenoma(FA) in whole genomic scale was needed prior to search on individual genes of possible causes. METHODS: Ten cases of PTC without ret/PTC-I, -2, -3 rearrangement and 5 cases of follicular adenoma were included in the study of microsatellite marker allelotyping. Sixty two microsatellite markers available, were chosen to cover the known sites of loss of heterozygosity(LOH) involved in thyroid tumors, tumor suppressor genes and terminal portion of each chromosomes. PCR was performed on tumor DNA and leukocytes DNA from each patient with MDE gel electrophoresis to detect LOH. Same specitnens as above, 3 case of normal thyroid tissues and NPA, ARO cell lines were included in the study of comparative genomic hybridization(CGH). Tumor and control DNAs were hybridized to metaphase chromosome with differential stainings with fluorescein and rhoda-mine-dUTP. Obtained results were analyzed by multicolor fluorescence computer assisted image analyzer. RESULTS: In allelotyping, LOH were detected in 5 cases of PTC, 2 cases on D10S1435, 1 case each on D2S1780, DSS1099, D11S1986, D16S539, 1 case of PTC revealed LOH on DSS1099, D11S1986. In FA, LOH were detected in 3 cases on D1S534, D1S226, Dl 1S907, D22S683, DXS9807. In CGH, Xp addition was noticed in 1 case of PTC, 12q and 10p addition was noticed in 1 case each, 16q deletion and 17q addition in 1 case of FA. CONCLUSION: No hot spot of LOH was noticed in microsatellite marker allelotyping, neither of common chromosomal change in CGH study suggesting unbalanced translocation or gene amplification more than 5-10 Mb may be involved in the genetic alteration of PTC and FA.
- A Case of Graves' Disease with Spuriously Elevsted TSH due to Interference of Heterophilin Actibodies.
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Jeong Hee Han, Sung Jin Lee, Young Rok Sin, Eun Ju Lee, Eun Sook Kim, Sang Wook Kim, Jin Yub Kim, Il Min Ahn
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J Korean Endocr Soc. 1999;14(1):160-164. Published online January 1, 2001
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- Thyroid-stimulating hormone (TSH) is the most sensitive marker reflecting thyroid function. TraditionaUy, TSH concentration was measured by the method of RadioImmunoAssay (RIA) with the detection limits around 1 to 2 mIU/L, which was unable to differentiate hyperthyroid status. Since 1980s, owing to the sensitive assay for TSH, immunoradiometric assay (IRMA), it has been possible to detect low concentration of TSH by 0.001 mlU/L. TSH is composed of two glycopeptide subunits, a-subunit and B-subunit. Monoclonal antibodies, directed against two different sites of the TSH peptides, are used in IRMA. One antibody is directed toward the specific B-subunit of TSH molecule and is used to extract it from serum, a second antibody labelled with a radioactive material is then attached to the separated TSH to form "sandwhich" molecule that can be measured. Generally, mouse monoclonal antibodies are used as capture and detection antibodies. Infrequently, when there is heterophilic antibody, i.e. human anti-mouse antibody (HAMA), TSH can be measured as spuriously elevated, since HAMA may form a link between the signal and capture molecules. We report a case of inappropriately elevated TSH concentration due to heterophilic antibody, later diagnosed as Graves disease. A 41-year-old woman visited our clinic with the chief complaints of hand tremor, hyperphagia, weight loss for 3 months. Two years earlier, she underwent total colectomy due to colon cancer and had treat on multiple chemotherapies. The results of thyroid function test shows that TSH was 0.77 mIU/L, free T was 7.1 ng/dL (0.8~1.9), free T was 11.3 pg/mL (0.2~5.5). Thyroid specific auto- antibody results were anti-Tg-Ab 21.3 m/mL(0 100), anti-TPO-Ab 87.9m/mL(0100), TBIAb 7.8% (-15/15). Thyroid scan showed that radioactiveiodine uptake was increased and thyroid gland wasenlarged diffusely. Because TSH level was elevated, further evaluations were performed to differentiate with TSH producing pituitary tumor and pituitary resistance to thyroid hormone. Sellar MRI was normal, TRH stimulation test showed flat response. Since spurious elevation of TSH is possible at the presence of hetrophilic antibody, we rechecked TSH concentration after adding mouse monoclonal antibody to the patients serum with result of TSH less than 0.05 mIU/L. She was able to be diagnosed as Graves disease, and started with methimazole. Three months later, thyroid function test showed that TSH was 10.5 mIU/L, free T4 was 1.0 ng/dL, free T3 was 4.0 pg/mL. TSH level after removal the effect of heterophilic antibody with mouse monoclonal antibody was 0.71 mIU/L. Neutropenia was developed 5 months after methimazole therapy, to stop antithyroid medication. With the plan of radioactive iodine therapy if she relapses, she is being followed with periodic thyroid function test. We report a case of Graves disease with spuriously elevated TSH due to the effect of heterophilic antibodies.
- A Case of Ventricular Fibrillation Aassociated with Hyperthysoidism.
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Il Min Ahn, Young Il Kim, Eun Joo Lee, Mi Heon Lee, Young Ki Song, Yoo Ho Kim
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J Korean Endocr Soc. 1998;13(3):459-465. Published online January 1, 2001
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- The cardiovascular manifestations in hyperthyroidism are sinus tachycardia, paroxysmal supraventricular tachycardia, atrial flutter, atrial fibrillation, atrioventricular block, bundle branch block(especially right bundle branch block), angina pectoris, heart failure and cardiomyopathy. Of these, angina pectoris is commonly seen in hyperthyroidism with coronary artery disease and the potential mechanisms have been attributed to the increased metabolic demand and consequently increased cardiac work which result in the more demand of coronary blood flow than that can be delivered via a fixed atherosclerotic coronary artery stenosis. Hyperthyroidism associated anginas without underlying coronary artery stenosis have also been reported where the mechanism of these was suspected to be the coronary vasospasm. Ventricular fibrillation may occur in the thyrotoxic patients due to myocardial ischemia such as variant angina, but it is very rare in the condition without previous heart disease. A 30-year-old male was admitted to the hospital because of palpitation, weight loss and proptosis for the previous 3 months. There was no history of effort related chest pain, syncope, drug abuse or medical illnesses such as diabetes mellitus, hypertension. The laboratory results were, TSH: 0.38uU/mL(0.4~5,0 uU/mL), free T4: 8.9ng/dL(0.8~1.9ng/dL), TSH receptor antibody: 43.6%(-15~15%), antiTPO antibody: 5000 IU/mL(0~100 IU/mL). The initial EKG showed normal sinus rhythm. He was diagnosed as Graves disease with ophthalmopathy, class 3a and was put on propylthiouracil 200 mg po tid, propanolol 40 mg po tid and started solumedrol pulse therapy for the exophthalmos on the first day of admission. He was found to have generalized tonic seizure with apnea attack on second hospital day and twice thereafter. Ventricular fibrillation was documented at that time. DC cardioversion was performed with successful response. After the attack, he was treated as accelerated hyperthyroidism namely with increased dosage of propylthiouracil, dexamethasone and Lugols solution, The echocardiogram, treadmill test, ergonovine echocardiography, coronary angiography and electrophysiologic study disclosed no abnormalities. Further episodes of ventricular fibrillation didnt occur after being euthyroid state. In conclusion, we report a case of ventricular fibrillation associated with hyperthyroidism itself without underlying coronary artery disease with brief review of literatures.
- Percutaneous Ethanol Injection in Benigh Thyroid Nodules.
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Hong Kyu Kim, Il Min Ahn, Eun Joo Lee, Jin Yub Kim, Mi Heon Lee, Sung Jin Lee, Ho Kyu Lee
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J Korean Endocr Soc. 1998;13(3):373-383. Published online January 1, 2001
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Abstract
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- BACKGROUND
Percutaneous ethanol injection(PEI) performed in guidance of ultrasonography has been used in cases of thyroid cyst and autonomous functiong thyroid nodule(AFTN). We performed this study to determine the feasibility of PEI on the various type of benign cold nodules(solid, pure cyst, complex cyst) and AFTN. METHOD: Ninety patients(age 41+12 years; 83 women and 7 men) with hot and cold nodule were included in this study. All cases were subjected to FNAB, and sono-guided in cases of complex cyst, at least twice with results of colloid nodule. T4 suppression treatment was done for cold solid nodules for at least 6 months and cases which had partial response(50% or more volume reduction but no further volume decrease on T4 suppression) were included in this study. After PEI, we classified AFTN into three different response groups; complete response (normali- zation of TFT and thyroid scan finding), partial response(normalized freeT4 but suppressed TSH or persistently suppressed scan), or failure group. Each subtypes(solid, pure cyst, complex cyst) of cold nodules were also classified into three groups in accordance with volume reduction; complete response(above 90% of volume reduction), partial response(50-90%), and failure(below 50% or increase in size) group. RESULTS: Overall responses rate of PEI for benign thyroid nodule were complete; 70(78%), partial; 18(20%), and failure; 2(2%). In 27 cold solid nodules, complete response was observed in 23(85%) and partial response in 4(15%). In 11 pure cysts, complete response was observed in 7(64%), partial response in 3(27%), and 1 case(9%) of failure was lost after 1 trial of PEI. In 45 cases of complex cyst, complete response was observed in 36(80%), partial response in 8 (18%), and 1 case(2%) of failure was subjected to operation with pathology report of Hiirthle cell adenoma. In 7 cases of AFTN, complete response was observed in 4(57%) and partial response in 3(43%). We observed complications during PEI therapy such as transient neck pain(n=10), transient unilateral vocal cord palsy(n=l), and intracavitary hemorrhage(n=2), transient hypotension during ethanol injection(n 1). CONCLUSION: Our data suggest that efficacy of PEI(57%) in AFTN is inferior to conventional therapies like surgery and radioiodine, but still can be an alternative therapeutic modality in selected cases. In cold nodules, especially of solid type and complex cyst, PEI may have feasibility as a therapeutic modality in restricted cases. Further studies of prolonged follow-up for the possibility of neglecting occult malignancy are warranted.
- The Expression of the Bcl-2 Family Proteins in Thyroid Neoplasms.
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Il Min Ahn, Eun Sook Kim, Seok Jun Hong, Kyung Yub Gong, Tae Jin Lee, Jin Yub Kim, Sung Bae Kim, Sang Hee Kim
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J Korean Endocr Soc. 1998;13(3):359-365. Published online January 1, 2001
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Abstract
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- BACKGROUND
Proteins of the Bcl-2 family are intracellular membrane-associated proteins that regulate programmed cell death either positively or negatively by as yet unknown mechanism. Bcl-2 family proteins have an antiapoptotic function, such as the Bcl-2, the long form of Bcl-x and Mcl-l, or a proapoptotic function, like the short form of Bcl-x and Bax. To investigate the potential role of Bcl-2 family proteins in thyroid tumorigenesis, the authors examined the pattern of expression of the Bel-2 family proteins in various thyroid neoplasms. METHODS: Bcl-2 family proteins, including Bcl-2, Bcl-x, Mcl-1 and Bax proteins were immunohistochemically stained in 57 cases of various thyroid neoplasms using formalin-fixed and paraffin embedded tissues; 18 cases of papillary carcinoma, 6 cases of medullary carcinoma, 4 cases of anaplastic carcinoma, 10 cases of follicular adenoma, 9 cases of adenomatous goiter, and 10 autopsy cases of fetal thyroid galnd. The intensity and frequency of the immunostaining were evaluated with the program of Image-Pro Plus Version 3.0 for image analysis. RESULT: Consistent expression of Bcl-2, Mcl-1, and Bax proteins were present in the surrounding normal thyroid tissue, however the expression of Bcl-x protein was not observed. Compare to the expression patterns of adenomatous goiter, and fetal and surrounding normal thyroid tissues, papillary and anaplastic carcinomas showed the decreased Bcl-2 and increased Bcl-x protein expressions(p (0.05). Medullary carcinoma revealed the increased Bcl-x protein expression only(p 0.05). CONCLUSION: These data suggest that combined patterns of decreased Bcl-2 and increased Bcl-x protein expressions may eontribute to the carcinogenesis of thyroid cancers originated from thyroid follicular cells, and an increased expression of Bcl-x protein may be related to the pathogenesis of medullary carcinoma from parafollicular C cells.
- Prevalence of Gsa, ras, p53 Mutations and ret/PTC Rearrangement in Differentiated Thyroid Tumors of Korean Population.
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Il Min Ahn, Young Il Kim, Hyun Soo Park, Ki Young Park, Seok Jun Hong, Eun Joo Lee, Kyung Yub Gong
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J Korean Endocr Soc. 1998;13(2):189-197. Published online January 1, 2001
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- BACKGROUND
In thyroid tumor, ras, Gsa, p53 mutation and ret/FfC rearrangement have been reported with variable prevalences in different geographic regions. We studied the prevalences of these mutations and reammgement in thyroid tumors of Korean population. METHODS: Eleven cases of adenamatous goiter, 8 cases of follicular adenoma, 5 cases of foliicular carcinoma, 37 cases of papillary carcinoma were included in this study. To find mutations and rearrangement, RT-PCR, SSCP, and/or direct sequencing, after subcloning if necessary, were used. RESULTS: We could not find any rearrangment for ret/PTC-l, -2, -3 and mutations of Gsa. For ras oncogene, K and H-ras mutations were not found, but N-ras mutations, point mutation of CAA to CGA in codon 61, were detected in 1 follicular adenoma(12.5%, 1/8) and 1 follicular carcinoma(33%, 1/3). And p53 mutations were detected only in 1 case of papillary carcinoma (3%, 1/31: exon 8, codon 266 GGA-GAA). CONCLUSION: ret/PTC rearrangement, Gsa, ras and p53 mutations are relatively rare in differentiated thyroid neoplasms of Korean population, which may reflect the genetic and environmental differences from those countries with high prevalence.
- Expression of Human Sodium Iodide Symporter mRNA in Papillary Thyroid Carcinoma.
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Hong Kyu Kim, Il Min Ahn, Young Il Kim, Eun Sook Kim, Hyun Soo Park, Ki Young Park, Seok Jun Hong
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J Korean Endocr Soc. 1998;13(2):181-188. Published online January 1, 2001
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- BACKGROUND
The sodium iodide symporter(NIS) is a plasma membrane protein which is respoasibIe for iodide transport into thyroid cell. The cDNA sequence of NIS has recently been cloned from rat and human. Intrinsic ability and its differences in iodide accumulation have been exploited as a useful tool for diagnosis and therapy of thyroid diseases. It is also known that some differentiated thyroid cancers do not take up radioactive iodine at therapeutic dose. METHODS: To understand the expression and regulation of NIS in thyroid tumars, we measured the expressons of human NIS(hNIS), TSH-receptor(R), and thyroglohulin(Tg) mRNAs from papillary thyroid carcinoma(PTC) tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) and RNase protection assay(RPA). RESULT: By RT-PCR analysis, 87% of PTC expressed hNIS mRNA, but the degree of expression were variable. Interestingly, 32% of PTC showed significant level of hNIS expression even though pre-operative technetium thyroid scan of all thyroid tumors were cold but the level was lower than normal control tissues. All of PTC showed the expressions of Tg and TSH-R mRNAs and there was a correlation between hNIS mRNA and TSH-R mRNA(Rsq 0.35, p=0.01). By RPA, the expression of hNIS and TSH-R in normal control tissue were detected with 20microgram and 40microgram of total RNA respectively, but the higher concentrations(> or =60microgram for hNIS and > or =40microgram for TSH-R) were required to detect in PTC, showing that tbe expression of hNIS in FTC was lower than TSH-R expression. CONCLUSION: PTC tends to lose hNIS mRNA expression earlier than TSH-R mRNA and the measurement of hNIS mRNA in PTC may be useful as an indicator of the therapeutic response to radioactive iodine.
- The Role of Low-dose ACTH Stimulation Test in the Diagnosis of Adrenal Insufficiency.
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Chul Hee Kim, Ghi Su Kim, Hong Kyu Kim, Joong Yeol Park, Young Kee Shong, Ki Up Lee, Il Min Ahn, Sung Kwan Hong
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J Korean Endocr Soc. 1997;12(2):222-229. Published online January 1, 2001
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Abstract
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Rapid adrenocorticotropin (ACTH) stimulation test using 250ug of ACTH (1-24) has been used as a standard test in the initial assessment of adrenal function. However, it has recently been suggested that a rnaximal cortisol response can be achieved with a much lower ACTH dose, and reducing the dose might further enhance the sensitivity of the test in the detection of mild adrenal insufficiency. This study was performed to evaluate the role of low-dose (lug) ACTH stimulation test in the assessment of adrenal function and the diagnosis of subtle adrenal insufficiency. METHODS: Twenty-two subjects with suspected adrenal insufficiency due to long-term corticosteroid use were included in this study. The correlations between clinical features and the serum cortisol responses to low dose (lug) and high dose (250 ug) ACTH stimulation were evaluated. RESULTS: In high dose test, 10 (67%) out of 15 subjects with clinical features of adrenal insufficiency showed decreased serum cortisol response (peak cortisol level <18 ug/dL), but 5 (33%) subjects showed normal response (peak cortisol level > 18ug/dL). On the other hand, 14 (93%) subjects with clinical features of adrenal insufficiency showed decreased serum cortisol response in low dose test, while only one showed normal response. In 7 subjects without clinical features of adrenal insufficiency, 5 subject (71%) showed normal response, and 2 subjects (29%) showed decreased response in both low and high dose tests. CONCLUSION: These results suggest that the 1-ug low dose ACTH stimulation test might be more sensitive than conventional 250-ug test in the detection of mild adrenal insufficiency. Further studies are needed to determine the optimal dose of ACTH and the criteria for normal response to ACTH stimulation.
- Controversies in the Diagnosis of Thyroid Nodules.
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Il Min Ahn
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J Korean Endocr Soc. 1996;11(4):377-382. Published online November 7, 2019
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- No abstract available.
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