Focal Lymphocytic Thyroiditis Nodules Share the Features of Papillary Thyroid Cancer on Ultrasound

Purpose: It is often difficult to discriminate focal lymphocytic thyroiditis (FLT) or adenomatous hyperplasia (AH) from thyroid cancer if they both have suspicious ultrasound (US) findings. We aimed to make a predictive model of FLT from papillary thyroid cancer (PTC) in suspicious nodules with benign cytologic results. Materials and Methods: We evaluated 214 patients who had undergone fine-needle aspiration biopsy (FNAB) and had shown thyroid nodules with suspicious US features. PTC was confirmed by surgical pathology. FLT and AH were confirmed through more than two separate FNABs. Clinical and biochemical findings, as well as US features, were evaluated. Results: Of 214 patients, 100 patients were diagnosed with PTC, 55 patients with FLT, and 59 patients with AH. The proportion of elevated thyrotropin (TSH) levels (p=0.014) and thyroglobulin antibody (Tg-Ab) or thyroid peroxidase antibody (TPO-Ab) positivity (p<0.001) in the FLT group was significantly higher than that in the PTC group. Regarding US features, absence of calcification (p=0.006) and “diffuse thyroid disease” (DTD) pattern on US (p<0.001) were frequently seen in the FLT group. On multivariate analysis, Tg-Ab positivity, presence of a DTD pattern on US, and absence of calcification in nodules were associated with FLT with the best specificity of 99% and positive predictive value of 96%. In contrast, a taller than wide shape of nodules was the only variable significant for differentiating AH from PTC. Conclusion: Suspicious thyroid nodules with cytologic benign results could be followed up with US rather than repeat FNAB, if patients exhibit Tg-Ab positivity, no calcifications in nodules, and a DTD pattern on US.ope

Therapeutic effect of protocatechuic aldehyde on graves' orbitopathy in an in vitro model

Dept. of Medical Science/석사Graves’ disease (GD) is an autoimmune disorder caused by excessive secretion of thyroid hormones. Pathological symptoms are observed in the eyes of the patients with GD, and these symptoms are called “Graves’ orbitopathy” (GO). The general symptom of GO is exophthalmos caused by increased connective tissue volume within the orbital. I investigated the therapeutic effect of protocatechuic aldehyde (3,4-dihydroxybenzaldehyde; PCA ) in an in vitro GO model. The experiments were carried out using orbital fibroblasts, which were cultured primarily from orbital fat tissue obtained after orbital decompression.I performed a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay to confirm the anti-oxidizing effect of PCA, and an 3-(4,5-dimethylthiazol-2-yl)-5-(3 carboxymeth`oxyphe nyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay to confirm the effect of PCA on the viability of normal and GO orbital fibroblasts. The anti-oxidant effect of PCA on reactive oxygen species (ROS) generation was stimulated with hydrogen peroxide (H2O2) and detected with 5-(and-6)-carboxy-2'',7''-difluorodihydrofluorescein diacetate (carboxy-H2DFFDA) by fluorescence activated cell sorting analysis. In addition, the expression of anti-oxidant enzyme heme oxygenase (HO) -1 was confirmed. The inhibitory effect of PCA on tumor necrosis factor (TNF) -α induced intercellular adhesion molecule (ICAM) -1 expression and hyaluronan production was determined by western blot analysis and a hyaluronan enzyme-linked immunosorbent assay (ELISA), respectively. To evaluate anti-adipogenic activities, PCA was added to adipose differentiation media, which included peroxisome proliferator activator gamma (PPAR-γ) agonist. After differentiation, the cells were stained with Oil red O, and adipose differentiation related protein expression of PPAR-γ, CCAAT-enhancerbinding proteins (c/EBP) -α, and -β, was confirmed by western blot analysis. DPPH assay results confirmed the free radical scavenging effect of PCA after treatment. Results of the MTS assay confirmed that PCA did not have any significant effect on cell viability. However, PCA had a suppressive effect on intracellular ROS generation and upregulated HO-1 expression by western blot analysis. PCA attenuated TNF-α induced ICAM-1 protein expression and inhibited hyaluronan production in a dose-dependent manner. Based on the results of Oil Red O staining, treatment with PCA during adipose differentiation, caused an decrease in lipid droplets, and expression of related proteins, including PPAR-γ c/EBP-α, and c/EBP-β was suppressed. I confirmed that PCA has anti-inflammatory, anti-oxidant, anti-adipogenic and inhibitory effects on hyaluronan production in vitro. With further research and clinical studies, I believe that PCA can potentially be used as a novel therapy for GO.restrictio

Therapeutic effect of protocatechuic aldehyde on graves' orbitopathy in an in vitro model

Dept. of Medical Science/석사Graves’ disease (GD) is an autoimmune disorder caused by excessive secretion of thyroid hormones. Pathological symptoms are observed in the eyes of the patients with GD, and these symptoms are called “Graves’ orbitopathy” (GO). The general symptom of GO is exophthalmos caused by increased connective tissue volume within the orbital. I investigated the therapeutic effect of protocatechuic aldehyde (3,4-dihydroxybenzaldehyde; PCA ) in an in vitro GO model. The experiments were carried out using orbital fibroblasts, which were cultured primarily from orbital fat tissue obtained after orbital decompression.I performed a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay to confirm the anti-oxidizing effect of PCA, and an 3-(4,5-dimethylthiazol-2-yl)-5-(3 carboxymeth`oxyphe nyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay to confirm the effect of PCA on the viability of normal and GO orbital fibroblasts. The anti-oxidant effect of PCA on reactive oxygen species (ROS) generation was stimulated with hydrogen peroxide (H2O2) and detected with 5-(and-6)-carboxy-2'',7''-difluorodihydrofluorescein diacetate (carboxy-H2DFFDA) by fluorescence activated cell sorting analysis. In addition, the expression of anti-oxidant enzyme heme oxygenase (HO) -1 was confirmed. The inhibitory effect of PCA on tumor necrosis factor (TNF) -α induced intercellular adhesion molecule (ICAM) -1 expression and hyaluronan production was determined by western blot analysis and a hyaluronan enzyme-linked immunosorbent assay (ELISA), respectively. To evaluate anti-adipogenic activities, PCA was added to adipose differentiation media, which included peroxisome proliferator activator gamma (PPAR-γ) agonist. After differentiation, the cells were stained with Oil red O, and adipose differentiation related protein expression of PPAR-γ, CCAAT-enhancerbinding proteins (c/EBP) -α, and -β, was confirmed by western blot analysis. DPPH assay results confirmed the free radical scavenging effect of PCA after treatment. Results of the MTS assay confirmed that PCA did not have any significant effect on cell viability. However, PCA had a suppressive effect on intracellular ROS generation and upregulated HO-1 expression by western blot analysis. PCA attenuated TNF-α induced ICAM-1 protein expression and inhibited hyaluronan production in a dose-dependent manner. Based on the results of Oil Red O staining, treatment with PCA during adipose differentiation, caused an decrease in lipid droplets, and expression of related proteins, including PPAR-γ c/EBP-α, and c/EBP-β was suppressed. I confirmed that PCA has anti-inflammatory, anti-oxidant, anti-adipogenic and inhibitory effects on hyaluronan production in vitro. With further research and clinical studies, I believe that PCA can potentially be used as a novel therapy for GO.restrictio

Therapeutic Effect of Resveratrol on Oxidative Stress in Graves' Orbitopathy Orbital Fibroblasts

PURPOSE: Multiple causative factors complicate the pathogenesis in Graves' orbitopathy (GO). It has been suggested that oxidative stress contributes to the development and progression of GO. Therefore, we investigated the therapeutic effect of resveratrol, a potent antioxidant, upon oxidative stress levels in GO orbital fibroblasts in vitro. METHODS: Orbital fibroblasts were cultured from orbital connective tissues obtained from GO patients. Intracellular reactive oxygen species (ROS) levels and the expression of heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase, and thioredoxin (Trx), were measured after resveratrol treatment. Adipogenesis was induced, and ROS levels were examined during adipogenic differentiation. Western blot assay was performed to evaluate the effects of resveratrol on the expression of antioxidants levels and transcriptional regulators. RESULTS: Treatment with 30 or 50 μM resveratrol reduced ROS production and HO-1 level induced by oxidative stress. Levels of Cu/Zn-SOD, catalase, and Trx were also reduced, while Mn-SOD increased with 50 μM resveratrol treatment. Resveratrol suppressed adipogenesis, reducing the number of adipocytes and suppressing the accumulation of lipid droplets. Treatment with 50 μM resveratrol also decreased ROS levels during adipogenesis. Expression of the transcriptional regulators phosphor-extracellular signal-regulated kinase and phospho-c-Jun NH(2)-terminal kinase significantly increased after treatment with 50 μM resveratrol, and decreased in response to inhibitors of each protein. Phosphonuclear factor kappa-light-chain-enhancer of activated B cells p65 levels also increased after treatment with 50 μM resveratrol. CONCLUSIONS: Resveratrol reduced ROS levels and inhibited adipogenesis in GO orbital fibroblasts in vitro. This study supports the potential use of resveratrol in GO treatment.ope