BACKGROUND: 4-1BB mediated costimulatory signal is a recently identified immunotherapeutic strategy for treating autoimmune diseases without depressing the immune response. In this study, we investigated the expression of 4-1BB and 4-1BBL on the peripheral blood mononuclear cells (PBMC) and we assessed whether the serum levels of soluble (s) 4-1BB and s4-1BBL in the patients with Graves' disease (GD) and compared them with normal subjects. METHODS: Expression of 4-1BB and 4-1BBL on PBMC of GD patients was determined by flow cytometry. The concentrations of s4-1BB and s4-1BBL were assessed in the sera of GD patients by performing ELISA. RESULTS: 4-1BB was constitutively expressed on naive CD4+ and CD8+ T cells of the GD patients and this was increased by stimulation. 4-1BBL was also expressed on the antigen-presenting cells such as CD19+ B cells, monocytes and dendritic cells in GD patients. The serum levels of s4-1BB and s4-1BBL were significantly higher in GD patients than those in controls, and these levels were significantly correlated with the serum levels of thyroid-binding inhibitory immunoglobulin and free T4. CONCLUSION: These results indicate that effector T cells of GD patients can be activated through the 4-1BB-mediated costimulatory signal. Elevated s4-1BB and s4-1BBL levels in the sera of GD patients may affect modulation of the clinical course in GD patients.
Antigen-Presenting Cells ; Autoimmune Diseases ; B-Lymphocytes ; Dendritic Cells ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Graves Disease ; Humans ; Immunoglobulins ; Monocytes ; T-Lymphocytes

Methimazole, a type of thionamide, is used to treat hyperthyroidism. Several adverse effects of thionamides have been reported. The representative minor adverse effects are arthralgia, skin rash, and gastric intolerance. Methimazole is reported to induce 1-6% of arthralgia cases. These patients begin to suffer from arthralgia from 1 month to 2 years after methimazole treatment. Here, we present a patient with acute onset methimazole-induced arthralgia and skin rash. At 2 days after starting methimazole treatment, a 57-year-old female developed arthralgia and a skin rash on her right leg, which subsequently spread to her left leg and right arm, and she stopped taking the medication. The patient was admitted to the rheumatology department of Ulsan University Hospital, where laboratory tests and a skin biopsy were performed to ascertain whether she had a rheumatic disorder. The skin biopsy revealed nonspecific inflammation. At 2 days after stopping methimazole treatment, the arthralgia and skin rashes had improved and methimazole treatment was recommenced. However, the same symptoms developed within 1 day. Therefore, methimazole treatment was again stopped and the symptoms disappeared.
Arm ; Arthralgia* ; Biopsy ; Exanthema* ; Female ; Humans ; Hyperthyroidism ; Inflammation ; Leg ; Methimazole ; Middle Aged ; Rheumatology ; Skin ; Ulsan

Insulin autoimmune syndrome is an uncommon cause of hypoglycemia. According to the type of antibody, it can be classified as caused by insulin or insulin receptor autoantibodies. Generally, insulin autoimmune syndrome develops following exposure to exogenous insulin or sulfhydryl medications, although insulin or insulin receptor antibody may also occur spontaneously. We treated a 54-year-old woman who developed spontaneous hypoglycemia. The patient had repeated hypoglycemia despite the infusion of dextrose solution. Her serum insulin, c-peptide, and insulin autoantibody were elevated, even during the hypoglycemic periods. Insulin receptor autoantibody and HLA-cw4/B62/DR4 were positive. After steroid and diazoxide treatment, the hypoglycemic symptoms improved gradually. No further hypoglycemic episodes occurred after tapering the medication over 1 year. We present a case of insulin autoimmune syndrome with positive insulin and insulin receptor autoantibodies.
Autoantibodies ; C-Peptide ; Diazoxide ; Female ; Glucose ; Humans ; Hypoglycemia ; Insulin ; Middle Aged ; Receptor, Insulin

PURPOSE: To assess the prevalence and the risk of malignancy in thyroid nodules which were cytologically diagnosed as follicular neoplasm by fine-needle aspiration (FNA) cytology. METHODS: All the patients who had undergone surgery with cytological diagnosis of follicular neoplasm from January 1996 through December 2001 in Asan Medical Center were studied retrospectively. Patients' and nodule characteristics were analyzed for factors associated with the presence of cancer. RESULTS: Two hundreds and fifteen patients (196 females, 19 males) were included and their mean age was 39.4 years (range: 12~76). About half of the patients (102 out of 215, 47.4%) had malignancy with 29 papillary carcinomas, 57 follicular carcinomas, 15 Hürthle cell carcinomas, and 1 medullary carcinoma. Previously suggested factors associated with risk for malignancy such as male gender, large tumor size (>4 cm), or age of patients (>45 years), were not associated with increased risk. Diagnosis of Hürthle cell neoplasia on FNA was also not associated with increased risk. Only the extreme age of the patients (below 20 or above 60 years) was associated with increased risk for malignancy. CONCLUSION: By our hands, prevalence of carcinoma in thyroid nodule patients with cytological diagnosis of follicular neoplasm was much higher than those reported. Clinical characteristics such as male gender, age, and nodule size, are not useful predictors for the presence of malignancy. Thyroid nodules with cytological diagnosis of follicular neoplasm warrant immediate surgery without any further work up.
Biopsy, Fine-Needle ; Carcinoma, Medullary ; Carcinoma, Papillary ; Chungcheongnam-do ; Diagnosis* ; Female ; Hand ; Humans ; Male ; Prevalence ; Retrospective Studies ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroid Nodule*

Purpose: Self-management of diabetes is a significant challenge. This study aimed to assess diabetes self-care activities and barriers among Korean young adults with diabetes mellitus. Materials and Methods: This study recruited 209 Korean adults with diabetes, with an onset age of 20–39 years, from four university hospitals. Demographic characteristics and the Summary of Diabetes Self-Care Activities (SDSCA) measure and Diabetes Self-Care Barriers Assessment Scale for Older Adults (DSCB-OA) scores were assessed using questionnaires. Results: The average age of study participants was 32.9±6.1 years. Their self-care activities, including adherence to recommended diabetes medication (5.6±2.4) and number of diabetes pills (5.5±2.3) in the SDSCA measure, were the most well-performed activities among all domains. Responses to inspection of the inside of shoes in the foot care activity (0.8±1.5) and specific exercise sessions in the exercise activity (1.6±1.9) reflected poor levels of compliance. According to the DSCB-OA questionnaire, the mean diabetes self-care barrier of DSCB-OA was 20.6±5.0 of total score 45. The greater perceived barriers to self-care on the DSCB-OA were having difficulty exercising regularly (1.9±0.7) and eating three meals and snacks leading to weight gain (1.9±0.8). Conclusion Young adults with early-onset diabetes showed a greater barrier to regular exercise and poor compliance with foot care and blood sugar testing. Healthcare providers must strengthen their relationship with young adults with diabetes to provide more education and guidelines for lifestyle modification focused on exercise and to promote higher compliance with diabetic self-care activities for improving clinical outcomes.

In patients with primary aldosteronism who have bilateral adrenal incidentalomas, it is important to identify which adrenal gland is secreting excess aldosterone. Traditionally, adrenal vein sampling (AVS) has been performed for lateralization despite its invasiveness. Here we report a case of bilateral adrenal incidentaloma in which 18-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) was used to identify the functional adrenal mass. A 53-yr-old man was referred to our clinic due to bilateral adrenal incidentalomas (right: 1 cm, left: 2.5 cm) on computed tomography (CT). Given his history of colon cancer, FDG-PET/CT scanning was used to rule out metastasis. Although there was focal hot uptake lesion in the right adrenal gland, the patient was suspected primary aldosteronism clinically more than metastasis because of the patient's underlying hypertension with hypokalemia. It was consistent with the results of AVS. Based on these findings, we propose that FDG-PET/CT can be used instead of AVS to identify the source of primary aldosteronism between two bilateral adrenal incidentalomas.
Adrenal Gland Neoplasms/*diagnosis/pathology/radionuclide imaging ; Adrenal Glands/pathology/surgery ; Fluorodeoxyglucose F18/diagnostic use ; Humans ; Hyperaldosteronism/*diagnosis/pathology ; Hypertension/diagnosis ; Hypokalemia/diagnosis ; Male ; Middle Aged ; Positron-Emission Tomography and Computed Tomography

A 47-year-old male with recurrent abnormal behavior for ten years was referred to our clinic. He was diagnosed with insulinoma and cognitive dysfunction. Persistent hypoglycemia leads to a high risk of cognitive dysfunction in diabetic patients. However, cognitive dysfunction associated with insulinoma is rare. In this case study, cognitive dysfunction was confirmed by neurological testing.
Humans ; Hypoglycemia ; Insulinoma ; Male

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, and its progression is poorly controlled by existing therapeutic methods. Curcumin has been shown to suppress inflammation and angiogenesis. In this study, we evaluated whether curcumin could augment docetaxel-induced apoptosis of ATC cells. We also analyzed changes in nuclear factor kappaB (NF-kappaB) and cyclooxygenase-2 (COX-2) expression levels to delineate possible mechanisms of their combined action. METHODS: ATC cells were cultured and treated with curcumin and docetaxel alone or in combination. The effects on cell viability were determined by MTS assay. Apoptosis was assessed by annexin V staining and confirmed by flow cytometric analysis. Caspase, COX-2, NF-kappaB levels were assayed by Western blotting. RESULTS: Curcumin combined with docetaxel led to lower cell viability than treatment with docetaxel or curcumin alone. Annexin V staining followed by flow cytometric analysis demonstrated that curcumin treatment enhanced the docetaxel-induced apoptosis of ATC cells. Additionally, curcumin inhibited docetaxel-induced p65 activation and COX-2 expression. CONCLUSION: We conclude that curcumin may enhance docetaxel's antitumor activity in ATC cells by interfering with NF-kappaB and COX-2. Our results suggest that curcumin may emerge as an attractive therapeutic candidate to enhance the antitumor activity of taxanes in ATC treatment.
Annexin A5 ; Apoptosis* ; Blotting, Western ; Cell Survival ; Curcumin* ; Cyclooxygenase 2 ; Humans ; Inflammation ; NF-kappa B ; Taxoids ; Thyroid Gland* ; Thyroid Neoplasms*

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.
Diagnosis ; Electrons ; Female ; Humans ; Iodine ; Lymph Nodes ; Neoplasm Metastasis ; Radionuclide Imaging* ; Recurrence ; Retrospective Studies ; Thyroglobulin ; Thyroid Gland* ; Thyroid Neoplasms*

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
Adrenal Cortex Hormones ; Classification ; Decompression, Surgical ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Muscles ; Orbit ; Prospective Studies ; Somatostatin