- Effect of LiCl on Iodine Kinetics in Thyroid Cancer Cell Lines Transduced by Recombinant Adenovirus Containing Sodium Iodide Symporter(NIS) Gene.
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Won Bae Kim, Ja Young Song, Sung Min Han, Jeong Seok Yeo, Heui ran Lee, Young Kee Shong, Dae Hyuk Moon
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J Korean Endocr Soc. 2003;18(2):166-176. Published online April 1, 2003
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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.
- 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.
- 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.
- 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.
- A Case of Ectopic ACTH Syndrome Caused by Thymic Carcinoid Tumor and Localized by PET.
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Jong Chul Won, Sung Kwan Hong, Hyun Ju Lee, Sang Ook Kim, Yun Hee Jeong, Dae Hyuk Moon, Dong Kwan Kim, Kyung Yub Kong, Jae Sung Lee, Ki Soo Kim
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J Korean Endocr Soc. 1999;14(4):771-778. Published online January 1, 2001
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- Ectopic ACTH syndrome is frequently caused by lung cancer and uncommonly by other tumors such as thymic carcinoid. For its treatment, early diagnosis and complete resection is irresponsible, but some cases are remained unlocalized in spite of all diagnostic modalities. Here we report a case of ectopic ACTH syndrome which was localized by PET but could not be localized by conventional technique. A tumor at thymic area was ACTH secreting thymic carcinoid which was operated but couldnt resect completly. Glucocorticoid hypersecretion was persisted with chemotherapy, radiotherapy, and ketoconazole treatment. Patient died of sepsis after 12 months of diagnosis.
- 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.
- A Comparison Technetium-99m and Iodine-123 Scan in Thyroid Hot Nodules.
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Eun Sook Kim, Seok Jun Hong, Young Ki Song, Jin Sook Ryu, Dae Hyuk Moon, Ki Soo Kim
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J Korean Endocr Soc. 1999;14(2):339-345. Published online January 1, 2001
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Pertechnetate ( Tc) has been widely employed for thyroid imaging. While pertechnetate and radioiodide have usually similar results in identifying thyroid nodules, occasionally differences have been noted. We intended to observe that the thyroid nodules which appeared to be hot on pertechnetate and to compare them with the images by radioiodide. METHODS: 'I scan was performed to thirty-eight cases (mean age: 48.9 +/- 13.2) presenting as hot nodule on Tc scan. Thyroid function test and pathologic diagnosis were obtained in all patients. RESULTS: Of the 38 patients, 24 had euthyroidism, 13 had hyperthyroidism, and 1 had hypothyroidism. Thirty patients had adenomatous goiter, 4 papillary carcinoma, 3 Hashimotos thyroiditis, and 1 had HQrthle cell tumor. 28 of 38 patients showed similar images, but the remaining 10 patients(26.3%) revealed discordant images on Tc and 131I scan. Among the concordant cases, 23 had adenomatous goiter, 3 had papillary carcinoma, and 2 had Hashimotos thyroiditis. Among the discordant cases, 7 had adenomatous goiter, 1 had papillary carcinoma, 1 had Hashimotos thyroiditis, and 1 had HQrthle cell tumor. The incidence of malignancy was 10.7% of concordant cases, and 20% of discordant cases and was revealed statistically insignificant (p>0.05). CONCLUSION: We observed higher incidence of malignancy in patients presenting hot nodules on 99mTc scan than ever reported. Fine needle aspiration should be performed to all patients with hot nodules and the 'I scan would not be recommended for further diagnostic study.
- Effect of Radioactive Iodine Therapy in Patients with Scan-Negative, Thyroglobulin-Positive Thyroid Cancer.
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Eun Sook Kim, Seok Jun Hong, Jin Yub Kim, Young Ki Song, Jin Sook Ryu, Dae Hyuk Moon, Ki Soo Kim, Sang Wook Kim
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J Korean Endocr Soc. 1999;14(2):330-338. Published online January 1, 2001
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After total thyroidectomy the presence of detectable serum thyroglobulin(Tg) concentration is an index of residual or metastatic thyroid tissue and is usually well correlated with positive I whole body scan. However, it is not rare to find a patient with detectable serum Tg levels but without any uptake on I whole-body scan. At present it is not certain how to manage such patients. We performed whole body scan after administration of therapeutic dose of 131I to evaluate the usefulness of radioactive iodine therapy in the above setting. METHODS: Fifteen patients (4 males and 11 females, ranging in age from 17 to 74 years) were studied. They had been previously treated with total thyroidectomy for papillary thyroid cancer followed by therapy with 131I for ablation of their thyroid residue. Tg levels were determined by immunoradiometric assay method. 131I (100-200 mCi) therapy was administered and whole body scan was performed. 99mTc MIBI scans were taken in 9 patients. Follow up data of Tg were available in 12 patients at time interval of 6 12 months from the first study and treatment. RESULTS: Tg(on) levels of these patients were in a range of 2.2210 ng/mL (mean 36.1 +/- 59.1 ng/mL) and Tg(off) levels were 17.3 1,592 ng/mL (mean 197.3 +/- 400.3 ng/mL). After radioiodide therapy, Tg(on) levels were in 1.48.5 ng/mL (mean 11.0 +/- 13.5 ng/mL), Tg (off) were 11.9 478.0 ng/mL (mean 159.3 +/- 159.8 ng/mL). The Tg (on) levels were decreased significantly after RAI therapy, but Tg (off) levels had no significant difference, In 8 of the 15 patients (53.3%), posttreatment whole body scan showed definite positive uptakes which were not evident in pretreatment diagnostic scan. There were local recurrence in 3 cases, regional lymph node metastasis in 4 cases, and lung in I case. Diffuse hepatic uptake was definitely seen in 7 cases. The MIBI scan showed abnorml uptakes in 4 of 9 cases. CONCLUSION: The therapeutic usefulness of 100 to 200 mCi of 131I treatment in patients with 131I scan-negative and Tg-positive was unclear. And the MIBI scan was only partially effective. Further studies with other diagnostic and therapeutic approachs are required to evaluate the exact lesions and to improve prognosis.
- Comparosin of Pretreatment and Postreatment Whole Body Iodine-131 Scans in Patients with Differentiated Thyroid Carcinoma.
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Eun Sook Kim, Young Ki Song, Jin Sook Ryu, Dae Hyuk Moon
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J Korean Endocr Soc. 1999;14(2):323-329. Published online January 1, 2001
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Whole body 131I scan is routinely performed in the postoperative evaluation of patients with differentiated thyroid carcinoma to detect recurrence and functioning metastasis. Previous reports suggested that posttreatment whole body scan had higher rate of detecting metastatic lesions that were not visualized by pretreatment images. We observed the frequency of discordance of the two scans and analysed the clinical significances. METHODS: Forty-one patients with differentiated thyroid carcinoma underwent radioactive iodine-131 whole body scans after administration of diagnostic dose (4 mCi) and then therapeutic dose (100~200 mCi of iodine-131). The median age of the patients was 46.9 +/- 15.7 years (range, 17~76). RESULTS: In 16 of the 41 patients (39.0%), pretreatment scan showed additional uptakes that were not seen in the pretreatment scan. Serum thyroglobulin was elevated in 13 of the 16 patients. Of the 22 patients who had been received radioactive iodine therapy previously, eight patients showed new additional lesions in the therapeutic scans but there was no significance according to the history of radioactive iodine therapy, Addisional uptakes after therapeutic dose were noted in neck area in 9 cases, lung in 2 cases, bone in 4 cases and mediastinum in one case. Diffuse hepatic uptake was definitely seen in 7 cases and there were 2 cases whose scans showed liver uptake without any thyroid uptake. CONCLUSION: Posttreatment whole body scan is more sensitive to detect residual tissues and metastasis compared to the usual pretreatment diagnostic whole body scan, and it is suggested that posttreatment whole body scan should be routinely performed after 'I therapy in patients with differentiated thyroid carcinoma for exact evaluation.
- Thallium-291 Whole Body Scintigraphy in Postoperative Follow-up of Differentiated Thyroid Carcinoma.
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Eun Sook Kim, Hong Kyu Kim, Sung Jin Lee, Jin Sook Ryu, Dae Hyuk Moon, Young Kee Shong
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J Korean Endocr Soc. 1999;14(1):63-70. Published online January 1, 2001
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The advantages of thallium (Tl)-201 whole body scan in follow-up of patients with thyroid carcinoma include no need to discontinue thyroid hormone replacement, a shorter period of time between injection and imaging, a lower radiation dose, and preservation of affinity for subsequent therapeutic dose of 131I. To evaluate the reliability of whole body scintigraphy using Tl-201 in postoperative follow-up of thyroid carcinoma, this procedure was performed in patients after total thyroidectomy for thyroid carcinoma. The results were compared with those of 131I scintigraphy. METHODS: One hundred nineteen cases (119 patients) with a median age of 43 years (range, 20 85 years) were included in the study. After optimal endogenous thyroid-stimulating hormone stimulation (>50 mIU/mL), 131I (4 mCi) scan and Tl 201 (3 mCi) scan were simultaneously performed. Concomitantly serum thyroglobulin and anti-thyroglobulin antibody levels were checked. If abnormal findings on any of the scintigraphic methods or high levels of thyroglobulin (> 10 ng/mL) were detected, high dose (150~200mCi) 131I was administered as therapy and then whole body scans were performed repeatedly after the therapy. The presence or absence of thyroid cancer was established by pathologic, radiologic, and/or high dose 131I scan findings. RESULTS: In 12 patients, ll-201 scan revealed positive accumulations which were not found on 131I scan, of whom 9 had elevated thyroglobulin levels. In these cases, 5 cases were interpreted to have normal thyroid remnant and 7 cases showed pathologic findings (1 lung, 2 lymph node, 1 bone, and 2 lung and lymph node metastasis, and 1 false positive accumulation of thallium). Metastasis were confirmed histologically in 2 and radiologically in 5 cases. Negative Tl-201 scans, despite of positive 131I scans, occurred in 20 patients, of whom 6 had abnormal thyroglobulin levels. Seventeen cases were interpreted to have thyroid remnant, 2 cases were diagnosed to have thyroid carcinoma metastasis (1 lung, 1 lung and lymph node), and 1 case was not confumed. CONCLUSION: These results suggest that 131I scan is superior to 11-201 scan for detection of residual or metastatic differentiated thyroid carcinoma. However, the use of combined modalities may provide a higher diagnostic yield. TI-201 scan can be useful especially in cases in which 'I scan is negative despite of abnormal thyroglobulin levels.
- Technetium-99m sestamibi whole Body Scintigraphy in Postoperative Follow-up of Differentiated Thyroid Carcinoma.
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Hong Kyu Kim, Eun Sook Kim, Young Ki Song, Jin Sook Ryu, Dae Hyuk Moon
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J Korean Endocr Soc. 1998;13(4):572-579. Published online January 1, 2001
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Recently technetium-99m sestamibi (99mTc MIBI), which dose not require withdrawal of thyroid hormone, has been used for imaging of thyroid carcinoma. The aim of this study was to determine the clinical usefulness of Tc MIBI scintigraphy after total thyroidectomy for thyroid carcinoma. The results were compared with those of standard 131I scintigraphy. METHODS: One hundred twelve patients with a median age of 44 years (range, 14-76 years) were included in the study. After optimal endogenous thyroid stimulating hormone stimulation (>50 mIU/mL), whole body scintigraphy using 4 mCi of 'I and 20 mCi of Tc sestamibi were done simultaneously. Concomitantly serum thyroglobulin and anti-thyroglobulin antibody levels were checked. If abnormal findings on any of the scintigraphic methods or high levels of thyroglobulin (> 10ng/mL) were detected, diagnostic imaging studies were done to confirm the existence of the disease. And high dose (150-200 mCi) 'I was administered as therapy and then whole body scans were performed again after the therapy. The presence or absence of thyroid cancer was established by pathologic, radiologic, and/or high dose I scan findings. RESULTS: In 11 patients, Tc MIBI scan revealed positive accumulations which were not found on 131I scan, of whom 6 had elevated thyroglobulin levels. In these cases, 5 cases were interpreted to have normal thyroid remnant and 6 cases showed pathologic findings (2 lung, 1 lymph node, 1 lung and lymph node, 1 local recurrent cancer, and 1 false positive accumulation of 99mTc MIBI). Metastasis or residual cancer were confirmed histologically in 1 and radiologically in 4 cases. Negative 99mTc MIBI scans, despite of positive I scans, occurred in 9 patients, of whom 2 had abnormal thyroglobulin levels. Seven cases were interpreted to have thyroid remnant, 2 cases were confirmed to have lung metastasis, and another one was misinterpreted due to breast shadow. CONCLUSION: In conclusion, these results suggest that 99mTc MIBI scan may have similar sensitivity and specificity for the detection of residual or metastatic differentiated thyroid carcinoma. The 99mTc MIBI scan, especially in cases of negative 131I scan despite of abnormal thyroglobulin levels, can be used as a very useful complementary diagnostic tool.
- Autoantigenic Role of Variant Thyroperoxidase.
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Young Kee Shong, Dae Hyuk Moon, Ghi Su Kim
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J Korean Endocr Soc. 1996;11(1):61-67. Published online November 7, 2019
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Thyroperoxidase(TPO) is one of the most important autoantigens in autoimmune thyroid disorders and autoantibody to TPO is found in almost every patients with various autoimmune thyroid diseases. Human TPO was already cloned and the completed nucleotide sequences are well known. In human thyroid tissues, several variants mRNA's of TPO are found in addition to the wild type. Especially the variants lacking exon 10(TPOΔexon10) and exon 16(TPOΔ exon16) are found in very large amount in both normal and Graves thyroid tissues. The significance of these variants TPO mRNAs are largely unknown. The authors tried to investigate the autoantigenic role of these variant TPO. Methods : To produce variant TPO cDNAs, oligonucleotide directed mutagenesis was performed using cDNA for wild type human TPO as template. The produced variants cDNAs were transfected into Cos-7 cells and variants TPO proteins were tested against patients sera showing high titers of anti-TPO antibody. Results: Seven of 12 Graves sera reacted with TPOΔexon 10 and 8 Graves sera with TPOΔ exonl6. Eight of 15 Hashimoto sera reacted TPOΔexon16 and 9 with TPOΔexon16. The reactivity with variants TPO was not related to clinical findings. Conclusion: These two variant TPOs, that is TPOexon10 and TPOΔexon16, could act as an autoantigen if they were translated in vivo, and could play a role in autoimmune thyroid disease. Their exact role in the pathogenesis of autoimmune thyroid disorders are to be clarified.
- Clinical Significance of Thyrotropin Measurement as a Screening Test in Ambulatory Patients.
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Young Kee Shong, Hong Kyu Kim, Ghi Su Kim, Dae Hyuk Moon
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J Korean Endocr Soc. 1994;10(3):191-199. Published online November 6, 2019
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- The objective of this study is to determine the clinical significance of thyrotropin(TSH) measurement as a screening test in ambulatory patients. One hundred and nintynine patients with abnormal TSH levels detected at routine examinations were studied. The patients were examined and histories about the recent medications and nonthyroidal illness were taken. Additional thyroid tests were done including measuments of total T_3, free T_4, antithyroid autoantibodies, thyroid scan and radioiodine uptake. Of the total 199 patients, 107(54.7%) had thyroid diseases. 49 out of 101 patients with subnormal TSH had thyroid diseases, and the remainder had supressed TSH due to medications, associated nonthyroidal illness, and normal variations. 58 out of 99 patients with elevated TSH had thyroid diseases. Of those 47 patients whose TSH level was below 0.05 mIU/L, functional sensitivity of TSH assay in our laboratory, 37 had thyroid diseases. Of those 19 patients whose TSH level was above 7.0mIU/L, two times of upper normal limit, all had thyroid iseases.Simultaneous measurement of free T_4 disclosed 50(25.1%) out of total 199 patients with abnormal TSH levels had abnormal free T_4 values which is regarded as evidence of clinical thyroid dysfunction. In summary, a single measurement of TSH level alone seems to have high sensitivity but low specificity. Simultaneous measurement of free T_4 can reasonably compensate the low specificity of TSH measurement. In case of ambulatory patients without significant nonthyroidal illness, TSH values below functional sensitivity or above twice upper normal limit may predict thyroid disease and dysfunction with reasonable specificity.
- Simultaneous measurement of thyroid growth stimulating antibody and thyroid adenylate cyclase stimulating antibody using FRTL-5 cells in patients with Graves' disease.
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Young Kee Shong, Dae Hyuk Moon, Ki Up Lee, Myung Hae Lee, Munho Lee, Bo Youn Cho, Chang Soon Koh
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J Korean Endocr Soc. 1991;6(1):17-24. Published online January 1, 2001
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- No abstract available.
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