Alpha-Lipoic Acid Decreases Iodine Uptake in the Rat Thyroid Cell Line FRTL-5 / 대한갑상선학회지

BACKGROUND AND OBJECTIVES: Alpha-lipoic acid (ALA) is a naturally occurring fatty acid with strong antioxidant properties that exerts protective effects against harmful free radical damage. The aim of the present study was to assess the effect of ALA on iodine uptake and expression of sodium iodine symporter (NIS) using FRTL-5 cells. MATERIALS AND METHODS: Cells were treated with ALA for various time and doses, in the presence or absence of thyrotropin (TSH). Cell viability assay, iodine uptake assay and NIS promoter activity assay were performed. RESULTS: ALA increased NIS promoter activity. It showed an additive effect when concomitantly added with TSH. After 48 hours of incubation with ALA in the presence or absence of TSH, there was no difference in iodine uptake according to doses of ALA. After 72 hours of incubation with ALA and TSH, ALA decreased iodine uptake in dose-dependent way. CONCLUSION: ALA induced NIS gene transcription of FRTL-5, but suppressed iodine uptake in the presence of TSH. ALA may suppress iodine uptake through effect for post-translation stage of NIS protein.

Papillary Thyroid Carcinoma Hidden behind the Hot Nodule / 대한갑상선학회지

52-year-old woman was presented with palpitation and weight loss. Thyroid function test revealed low thyroid-stimulating hormone level with upper normal range of Free T4 and thyroid scan showed 2 cm hot nodule in left upper pole. Thyroid ultrasonography was also done and it showed two nodules in left upper pole. The one was considered as functioning benign nodule, but the other nodule was compatible with malignancy. She underwent total thyroidectomy and final pathology revealed papillary thyroid carcinoma.

Comparison of Different Staging Systems for Predicting Recurrence of Papillary Thyroid Carcinoma

BACKGROUND: Various staging systems for thyroid cancer that focus on cancer specific death have been suggested, but this approach had a limitation due to the relatively long clinical course and very low rate of cancer death. This study was performed to evaluate the staging systems and to determine the most predictive staging system for predicting recurrence. METHODS: The patients who underwent first total or near total thyroidectomy due to papillary thyroid cancer (PTC) at Asan Medical Center between January 1995 and December 2001 were the subjects of this study. The commonly used 8 staging systems were applied to these subjects. Disease free survival (DFS) and the relative importance of each staging system were determined by the Kaplan-Meier method, the Cox-proportional hazards model and the proportion of variation in the survival time explained (PVE). RESULTS: A total of 952 patients (M = 117, F = 835) were enrolled and their mean age was 45 years. During a median of 10 years of follow-up, 146 (15.3%) of 952 patients had recurred tumor. The independent prognostic factors were male gender, tumor size, extrathyroidal invasion and cervical lymph node metastasis. Risk stratification according to the American thyroid association (ATA) guideline was the most predictive staging system for recurrence of PTC (PVE 88.6%). The staging systems from EORTC (PVE 79.5%), and MACIS (PVE 68.4%) had significant values for predicting recurrence of PTC. The stage of NTCTCS could not predict recurrence (PVE 4.5%, P = 0.11). CONCLUSION: Risk stratification according to the ATA was most predictive staging system for predicting recurrence of PTC. The MACIS and EORTC staging systems have good value for predicting recurrence of PTC.

Takotsubo Cardiomyopathy: A Case of Persistent Apical Ballooning Complicated by an Apical Mural Thrombus

Takotsubo cardiomyopathy (TTC) is an infrequent cardiac syndrome characterized by acute onset chest pain with apical ballooning on echocardiography. It is often triggered by severe emotional or physical stress, and in contrast to acute myocardial infarction (AMI), the regional wall motion abnormality returns to normal within days. Here, we describe a 62-year-old female who presented with acute onset chest pain during treatment for a liver abscess. We presumed a diagnosis of AMI because of ST segment elevation on electrocardiography and elevated cardiac enzyme levels. However, the patient's coronary arteries were normal on angiography, and apical ballooning was seen on echocardiography. A diagnosis of TTC was made, and the patient was managed with intensive cardiopulmonary support using vasopressors in our hospital's medical intensive care unit. The patient's symptoms improved, but persistent severe left ventricular dysfunction was detected on follow-up echocardiography. After 5 weeks, a new apical mural thrombus appeared, and anticoagulation therapy was started. The apical ballooning persisted 3 months later, although the patient's overall ejection fraction was slightly improved. The apical thrombus was completely resolved without any embolic event. Non-adrenergic inotropics can be recommended in TTC with shock, and clinicians should keep in mind the potential risk of thrombus formation and cardioembolism.

Expression of X-linked Inhibitor of Apoptosis Protein in Neoplastic Thyroid Disorder

X-linked inhibitor of apoptosis protein (XIAP) is associated with tumor genesis, growth, progression and metastasis, and acts by blocking caspase-mediated apoptosis. In the present study, we sought to evaluate the expression patterns of XIAP in various neoplastic thyroid disorders and determine the association between XIAP expression and clinicopathologic factors. Expression of XIAP was evaluated with immunohistochemical staining using monoclonal anti-XIAP in 164 specimens of conventional papillary thyroid carcinoma (PTC) and 53 specimens of other malignant or benign thyroid tumors. XIAP positivity was observed in 128 (78%) of the 164 conventional PTC specimens. Positive rates of XIAP expression in follicular variant PTC, follicular, medullary, poorly differentiated, and anaplastic thyroid carcinoma specimens were 20%, 25%, 38%, 67%, and 38%, respectively. Six nodular hyperplasia specimens were negative and 1 of 7 follicular adenomas (8%) was positive for XIAP. Lateral neck lymph node metastases were more frequent in patients negative for XIAP expression (P = 0.01). Immunohistochemical staining for XIAP as a novel molecular marker may thus be helpful in the differential diagnosis of thyroid cancer. Moreover, high XIAP expression in conventional PTC is strongly associated with reduced risk of lateral neck lymph node metastasis.

Predictive Factor for Therapeutic Results after Intravenous Glucocorticoid Therapy in Thyroid-Associated Ophthalmopathy / 대한갑상선학회지

BACKGROUND AND OBJECTIVES: Little has been known for factors predicting improvement of proptosis in patients with thyroid-associated ophthalmopathy (TAO) after intravenous (IV) glucocorticoid therapy. This study aimed to evaluate the efficacy of IV glucocorticoid therapy and to find factor predicting treatment outcomes in patients with TAO. MATERIALS AND METHODS: Forty-two consecutive patients with TAO treated by IV glucocorticoid from 2000 to 2009 were retrospectively analyzed. They received IV methylprednisolone of 7.0 g over 18 weeks. Before and after treatment, patients underwent orbital CT for assessment of proptosis and extraocular muscle hypertrophy, and physical examination for clinical activity score (CAS). RESULTS: Thirteen patients (31%) showed improvement in proptosis after therapy. High extraocular muscle diameter index was an independent predictor for improvement in proptosis (odds ratio=1.25, p=0.03). Smoking, age, gender and initial CAS did not predict improvement. Seven of 16 patients with initial CAS or =3 (77%) showed improvement in diplopia after treatment (p=0.002). Of patients with CAS> or =3, patients with intermittent, inconstant and constant diplopia showed improvement in diplopia in 100%, 80% and 63%, respectively. Of patients with CAS<3, patients showed improvement in 80%, 33% and 20%, respectively. CONCLUSION: Presence of extraocular muscle hypertrophy was the only factor predicting improvement in proptosis after IV glucocorticoid therapy. In patients with TAO, IV glucocorticoid therapy could be considered to improve proptosis when they present with increased extraocular muscle diameter, or to improve diplopia especially when they also have high initial CAS.

Metastatic Lung Nodule of Thyroid Papillary Carcinoma, Mimicking Primary Lung Cancer / 대한갑상선학회지

No abstract available.

Four Cases of Malignant Pleural Effusion in Patients with Papillary Thyroid Carcinoma

Papillary thyroid carcinoma could be a rare cause of malignant pleural effusion. The development of malignant pleural effusion in patients with papillary thyroid cancer is an extremely adverse prognostic indicator. Here, we report four cases that showed development of malignant pleural effusion during the clinical course of the papillary thyroid carcinoma and consider the prognosis. In four patients, the median survival time after the development of malignant pleural effusion was only 17 months.

Response: Postoperative Findings of the Cytological Diagnosis of Follicular Neoplasm or Hurthle Cell Neoplasm and the Risk of Malignancy

No abstract available.

Effect of sunitinib on the proliferation and survival of FRTL-5 cells / 대한내과학회지

BACKGROUND/AIMS: Hypothyroidism has been reported in 36~85% of patients treated with sunitinib for renal cell carcinoma or gastrointestinal stromal tumor. However, the mechanism behind this hypothyroidism is unclear. This study evaluated the effects of sunitinib, a multi-target tyrosine kinase inhibitor, on the survival and proliferation of thyrocytes using FRTL-5 rat thyroid cells. METHODS: We examined the effect of sunitinib on cell proliferation in the presence and absence of thyroid stimulating hormone (TSH) in a colorimetric assay. Effects on the cell cycle were evaluated by flow cytometry, and on apoptosis using an annexin V apoptosis assay kit and by immunoblotting for caspase-3. Immunoblotting was also used to evaluate changes in the levels of intracellular proteins associated with the G1-S phase of the cell cycle. RESULTS: Sunitinib suppressed the proliferation of FRTL-5 cells in a dose- and time-dependent manner. This suppressive effect was enhanced by the presence of TSH (1 mU/mL). Sunitinib was subsequently shown, in flow cytometric analyses, to arrest the cell cycle at the G1-S phase. Furthermore, it induced apoptosis at a high concentration (15 micrometer) by activating caspase-3. G1-S phase arrest was associated with the induction of p27(kip1) and p21(cip1), whose expression is suppressed by TSH under control conditions. Sunitinib also decreased intracellular levels of cyclin D1 and cyclin-dependent kinase 2 in FRTL-5 cells. CONCLUSIONS: Sunitinib induced apoptosis in and suppressed the proliferation of FRTL-5 cells. Its suppression of proliferation was further enhanced by the presence of TSH. Sunitinib arrested the cell cycle in the G1-S phase by inducing the expression of p27(kip1)/p21(cip1), which are suppressed by TSH under normal conditions. Collectively, these findings suggest that sunitinib may interfere with TSH signaling pathways in normal thyrocytes.

Postoperative Findings of the Cytological Diagnosis of Follicular Neoplasm or Hurthle Cell Neoplasm and the Risk of Malignancy

BACKGROUND: Follicular neoplasm (FN) or Hurthle cell neoplasm (HN) is a less well understood pitfall when evaluating thyroid nodule with fine-needle aspiration (FNA). This study aimed to determine the rates of malignancy and the predictive factors for malignancy in thyroid nodules with a cytological diagnosis of FN or HN. METHODS: The patients who were cytologically diagnosed as having FN or HN after FNA between 1995 and 2004 at Asan Medical Center were included in this study. We collected the pathology data until 2009 and we analyzed the clinical characteristics associated with malignancy. RESULTS: A total 478 patients were cytologically diagnosed as having FN or HN during the study period and 327 (68%) among them underwent thyroid surgery. Thyroid malignancy was confirmed in 157 (48%) of 327 patients. Malignancy was confirmed in 124 patients with FN (124/253, 49%). They were 48 papillary, 65 follicular, 7 Hurthle cell and 3 medullary carcinomas and 1 anaplastic carcinoma. The malignancy in the cases of HN (33/71, 44.6%) was 9 papillary, 4 follicular and 20 Hurthle cell carcinomas. The risk of malignancy was not associated with male gender, a larger tumor size (> 4 cm) or the diagnosis of HN. However, an age below 20 years (RR 3.6, P = 0.03) and above 60 years (RR 2.3, P = 0.04) was associated with an increased risk of malignancy. CONCLUSION: About half of the patients with FN or HN on FNA cytology were diagnosed as having thyroid cancer after surgery. The malignancy rate for the cytologic diagnosis of HN was similar to that for FN. Thyroid surgery should be recommended for this situation, and especially for patients younger than 20 years or older than 60 years.

Clinical impact of aspirin resistance measured using the Ultegra Rapid Platelet Function Assay-ASA in patients undergoing percutaneous coronary intervention / 대한내과학회지

BACKGROUND/AIMS: Aspirin resistance is reported to be associated with myocardial infarction, stroke, and myonecrosis after percutaneous coronary intervention. However, aspirin resistance and its clinical implications in patients undergoing drug-eluting stent (DES) implantation have not been evaluated sufficiently. METHODS: The study enrolled 419 consecutive patients who underwent DES implantation. All of the patients took aspirin 100 mg (228 patients, 54.4%) or 200 mg (191 patients, 45.6%). Aspirin resistance was measured using the Ultegra Rapid Platelet Function Assay-ASA (Accumetrics, San Diego, CA, USA). The results were expressed as aspirin reaction units (ARU). Aspirin resistance was defined as ARU > or =550. We followed all patients for 9 months. RESULTS: Aspirin resistance was found in 33 patients (33/419, 7.9%). The aspirin dose (118.18+/-39.2 vs. 147.93+/-50.0 mg, p= 0.011) was lower in the aspirin-resistant (n=33) versus the aspirin-sensitive (n=386) group. There was no significant difference in the occurrence of myocardial necrosis (15.6% vs. 15.5%, p=0.988). On multivariate analysis, low-dose aspirin (odds ratio (OR) 4.714; 95% confidence interval (CI) 1.865-11.914; p=0.001), age (OR 1.048; 95% CI 1.005-0.092, p=0.029), platelet count (OR 1.007; 95% CI 1.001-1.014, p=0.011), and hypercholesterolemia (OR 2.937; 95% CI 1.310-6.583, p=0.009) were independent predictors of aspirin resistance. Over the 9 months, no stent thrombosis or death occurred; one acute myocardial infarction occurred in the aspirin-sensitive group. CONCLUSIONS: Low-dose aspirin, old age, a higher platelet count, and hypercholesterolemia were associated with a high incidence of aspirin resistance in patients who underwent DES implantation. However, no significant differences in clinical outcome were found between the aspirin-resistant and -sensitive groups during a 9-month follow-up.

A Case of Bronchial Obstruction Due to Bronchial Angulation after Upper Lobectomy / 결핵및호흡기질환

A bronchial obstruction of the remaining lung is a rare complication of thoracic surgery. We report a case of this rare complication after a right upper lobectomy due to a giant bulla. Post-resectional angulation of the bronchus intermedius caused the bronchial obstruction. An intrabronchial stent was inserted into the bronchus intermedius, which relieved the obstruction.