Percutaneous Ethanol Injection in Autonomous Functioning Thyroid Nodules and Complex Cysts: Five Years' Experience / 대한내분비학회지

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

Diagnostic adequacy of ultrasound-guided fine needle aspiration in thyroid nodules / 대한내과학회지

BACKGROUND: Fine needle aspiration (FNA) is regarded as initial diagnostic procedure for thyroid nodules due to its accuracy and safety. One of the limitations of FNA is variable rate of inadequate specimen. Recently, ultrasound guidance has been suggested as a valuable method to improve diagnostic performance of FNA. The aim of this study is to evaluate the rates of adequate specimen when FNA is done with ultrasound guidance. METHODS: This study was performed on 304 patients who underwent ultrasound-guided FNA for thyroid nodules. Ultrasound-guided FNA was performed due to various causes. RESULTS: Inadequate specimens were obtained from 62 patients (20.4%). The sizes of thyroid nodules from which specimen obtained were 1.63+/-1.17 cm for adequate specimen, 1.18+/-0.72 cm for inadequate specimen respectively and differed significantly (p=0.001). When patients were divided by the size of thyroid nodules, the rates of inadequate specimen were significantly different between the groups above 1.5 cm and less than 1.5 cm (p=0.04). The rates of inadequate specimen were also different according to the indications of ultrasound guidance, 25.4% in nonpalpable thyroid nodules and 11.4% in complex cysts. When complex cyst group was divided by the size of thyroid nodules, the rates of inadequate specimen were not different. CONCLUSION: There are less benefits of ultrasound-guided FNA for patients with nodule size less than 1.5 cm. We recommend ultrasound guidance for patients with complex cyst rather than nonpalpable thyroid nodules.

Effectiveness of Percutaneous Ethanol Injection in Benign Cold Thyroid Nodules: Five Years' Experience / 대한내분비학회지

BACKGROUND: 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

A Case of Hashimotos Thyroiditis with Anti-Triiodothyronine Autoantibody / 대한내분비학회지

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.

Lanreotide Therapy in Graves' Ophthalmopathy / 대한내분비학회지

BACKGROUND: 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

Clinical Applications of 18-FDG PET in Recurred Differentiated Thyroid Cancer with Negative 131I Whole Body Scintigraphy: A Comparative Analysis with 99mTc-MIBI Scintigraphy / 대한내분비학회지

BACKGROUND: In patients with differentiated thyroid cancer treated by surgery and radioactive iodine ablation, serum thyroglobulin(Tg) and 131I whole body scan(WBS) are recognized as being the best cooperative indicators for detection of recurrence or metastasis. However, in some cases, 131I WBS shows no specific lesions despite elevated serum Tg. Therefore, 18-Fluorine-fluorodeoxyglucose (FDG) positron emission tomography(PET) has emerged as a useful method for the detection of 131I WBS negative thyroid cancers. The aims of the present study are to evaluate the clinical usefulness of this technique in detection and to compare the results with 99mTc-MIBI scintigraphy(MIBI) in cases of final results being confirmed by histologic diagnosis and other imaging methods. METHODS: We conducted a retrospective analysis amon 131I WBS negative recurred papillary thyroid carcinoma patients(male: female ratio=9:22, median age=42 yr). FDG PET was performed in 28 patients and MIBI 28 patients, 25 of whom were common to both groups. All patients had histologically proven recurrence/metastasis and negative 131I WBS results but persistently elevated serum Tg levels. In each case overall clinical evaluations were performed including histology, cytology, thyroglobulin level, other imaging methods, posttherapy 131I WBS and subsequent clinical course, to allow comparison with the results of FDG PET. RESULTS: In 19 cases of patients with negative 131I WBS, proven recurrence/metastasis lesions were detected in FDG PET. Compared with MIBI, FDG PET was found to be superior in 8 cases(including 2 patients with distant metastases). No FDG-negative/MIBI-positive tumor was observed. One FDG PET negative and MIBI negative case was proven 3 months later to be metastatic cervical lymph nodes, Sensitivities were 94.7% in the FDG PET group and 52.6% in MIBI. Diagnostic accuracy of FDG PET was superior to that of MIBI(93% vs. 62%, respectively, p=0.003). CONCLUSION: Our results confirmed the clinical usefulness of FDG PET for detection of 131I negative differentiated thyroid cancers and suggested the value of FDG PET as an initial diagnostic step, rather than MIBI, in these cases.

The Value of FDG-PET in Reoperation of the Recurrent Papillary Thyroid Carcinoma with Elevated Thyroglobulin Levels and Negative I131 WBS

PURPOSE: We evaluated the diagnostic accuracy and useful ness of FDG-PET to determine the proper extent of surgery in recurrent papillary thyroid cancer patients with elevated thyroglobulin levels and negative I131 WBS. METHODS: FDG-PET was performed in 16 recurrent papillary thyroid cancer patients with elevated thyroglobulin levels and negative I131 WBS. In 9 patients, FDG-PET was performed to localize the recurrent lesions. In 7 patients, the recurrent lesions were initially diagnosed by physical examination or other image studies and the FDG-PET was subsequently performed to detect additional recurrent lesions. All suspected lesions detected by FDG-PET and other studies were explored. RESULTS: Among the 9 patients in whom FDG-PET was performed to localize the recurrent lesions, the recurrent lesions were detected only by FDG-PET in 4 patients. Among the 7 patients in whom FDG-PET was performed additionally to detect additional recurrent lesions, another recurrent cervical regions were detected by FDG-PET in 2 patients. However, the same lesions were able to be identified by ultrasonography. A total of 26 cervical regions were explored in 16 patients. There were 4 FDG-PET false positive regions and 2 FDG-PET false negative regions. Unnecessary surgery was performed in 4 cervical regions in 4 patients. CONCLUSION: FDG-PET was very useful in detecting small early recurrent lesions but was unable to contribute to the detection of additional recurrent cervical regions in the pa-tients in which the recurrent lesion had already been by physical examination or other studies. Other image studies are necessary to supplement the FDG-PET in false positive or false negative cases.

Differential Diagnostic Value of TSH Receptor Antibody Measurements in Thyrotoxic Postpartum Patients with History of Graves' Disease / 대한내분비학회지

BACKGROUND: 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 Value of Central Neck Exploration in Reoperation for Recurrent Papillary Thyroid Carcinoma

PURPOSE: Central neck recurrence in papillary thyroid cancer patients is critical because it is closely related to mortality. We examined value of the central neck exploration in reoperation for recurrent papillary cancer. METHODS: 70 recurrent papillary cancer patients who underwent reoperation from Jan 1996 to July 2000 were reviewed retrospectively. The patients were divided into 3 groups: lateral neck recurrence group (group L, 31 cases), lateral neck and central neck combined recurrence group (group LC, 19 cases), and central neck recurrence group (guoup C, 20 cases). In the 19 cases of group LC, bilateral paratracheal exploration was performed in 10 cases and unilateral paratracheal exploration was completed in 9 cases. Among these, 5 paratracheal areas were negative according to preoperative study and were explored blindly. The remission (serum thyroglobulin

Enhanced Effect of Iodide - Uptake in Thyroid Carcinoma Cells by Infecting Adenovirus - Human Sodium Iodide Symporter (Ad - hNIS) / 대한내분비학회지

BACKGROUND: 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.

The Role of Preoperative and Postoperative Thyroglobulin Measurements in The Detection of Well Differentiated Thyroid Carcinomas Recurrence / 대한내분비학회지

BACKGROUND: 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.

Clinical Significance of Human Sodium Iodide Symporter mRNA Expressions in Primary and Metastatic Papillary Thyroid Carcinoma / 대한내분비학회지

BACKGROUND: 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.

FDG-PET as a Predictor of Recurrence with 131I Scan Negative Differentiated Thyroid Cancer: An Evaluation Compared with Pathologic Findings / 대한내분비학회지

BACKGROUND: 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 Case of Graves' Disease with Spuriously Elevsted TSH due to Interference of Heterophilin Actibodies / 대한내분비학회지

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.

Parathyroid Glands Location, vascular supply and preservation during a total thyroidectomy

BACKGROUND: It is well known that the inferior parathyroids are more difficult to preserved than the superior parathyroid glands because the inferior parathyroid glands have more anatomical variations. METHODS: The authors analysed the gross surgical findings of a total of 411 inferior parathyroid glands in 314 total thyroidectomy cases. The inferior parathyroid glands were grouped according to patterns based on their location and arterial blood supply. RESULTS: Type 1 (location: posterior surface of the lower thyroid pole; artery: inferior branch of the inferior thyroid artery): incidence 51% and presevation rate 62%. Type 2 (location: thyrothymic ligament or in the thymus; artery: inferior branch of the inferior thyroid artery): incidence 27% and preservation rate 86%. Type 3 (location: apart from the lower thyroid pole; artery: inferior branch of the inferior thyroid artery): incidence 6.1% and preservation rate 92%. Type 4 (location: anteriorly on the lower thyroid pole; artery: inferior branch of the inferior thyroid artery): incidence 4.1% and preservation rate 33%. Type 5 (location: lower thyroid pole; artery: comes out from the thyroid gland): incidence 4.1% and preservation rate 0%. Type 6 (location: lower thyroid pole; artery: branch of the superior thyroid artery): incidence 3.6% and preservation rate 80%. Type 7 (location: lower thyroid pole; artery: embedded in the thyroid gland): incidence 2.9% and preservation rate 36%. Type 8 (location: more superior than usual; artery: superior branch of the inferior thyroid artery): incidence 0.7% and preservation rate 67%. Type 9 (location: lower thyroid pole; artery: thyroid ima artery): incidence 0.5% and preservation rate 100%. CONCLUSIONS: The most identified inferior parathyroids belonged to the usual types, and their pre-servation rate were relatively high. However there were some unusual types though their incidence was low. Thus, accurate anatomical knowledge of variations in the location and the blood supply of the inferior parathyroids is needed to enhance the preservation rate.

Allelotyping and Comparative Genomin Hybridization Studies in Papillary Thyroid Carcinomas and Follicular Adenomas / 대한내분비학회지

BACKGROUND: 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.

Sono-Guided Ethanol Sclerotherapy for Benign Thyroid Csts: Results in 22 Cases

PURPOSE: To evaluate the efficacy and safety of sono-guided ethanol sclerotherapy for benign thyroid cysts. MATERIALS AND METHODS: We studied 22 patients with benign thyroid cysts (9 pure and 13 complex) confirmed by fineneedle aspiration biopsy. The procedure was performed every one or three months for a total of one or twosessions(mean 1.2 times). Sono-guided needle aspiration of the cysts was followed by instillation of absoluteethanol(99.9%) into the cystic cavity ; the injected volume of ethanol was 40-100% that of aspirated fluid.Follow-up ultrasonography was performed one to ten months( mean: 3.5 months) after the final session, andcomplications occurring after ethanol sclerotherapy were observed. RESULTS: Initial cystic volume was3.5-42(mean: 13)ml. In 21 patients( 95%), cystic volume had decreased: In 13 patients(59%), the decrcase was 50%or more, and in six (27%) was 1-49%. In two patients(9%), the cysts had been obliterated, but in one there was nochange. The volume of instilled ethanol correlated significantly with the volume reduction rate of the cyst (p<0.01, t test). After ethanol sclerotherapy, the volume of thyroid cysts larger than 10ml had significantlydecreased compared to that of thyroid cysts with a volume less than 10 ml(p< 0.005, t test). Importantlongstanding and severe complications were not observed ; in two patients, a small amount of leakage insubcutaneous tissue caused local pain and redness. CONCLUSION: Sono-guided ethanol sclerotherapy is a safe andeffective tool for the treatment of benign thyroid cysts.

The Expression of the Bcl-2 Family Proteins in Thyroid Neoplasms / 대한내분비학회지

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.

Percutaneous Ethanol Injection in Benigh Thyroid Nodules / 대한내분비학회지

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.

Expression of Human Sodium Iodide Symporter mRNA in Papillary Thyroid Carcinoma / 대한내분비학회지

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.