Risk factors for hypothyroidism in euthyroid thyroid nodule patients with lymphocytic thyroiditis on fine needle aspiration cytology.

BACKGROUND/AIMS: Lymphocytic thyroiditis as cytology diagnosis from fine needle aspiration (FNA) is frequently detected in patients with thyroid nodules. However, the clinical outcome for upcoming hypothyroid events has been rarely clarified in euthyroid patients. METHODS: We retrospectively reviewed the data of patient who had lymphocytic thyroitidis on FNA cytology of thyroid nodule from January 2005 to December 2010 at a tertiary referral hospital. In total, 109 patients with follow-up thyroid function tests (TFT) were enrolled. Final outcomes included overt and subclinical hypothyroidism with thyroid stimulating hormone (TSH) levels ≥ 10 mIU/L. Potential parameters predicting clinical hypothyroidism were analyzed by multivariate analysis. RESULTS: Over the mean follow-up duration of 51.6 months, 14 out of 109 patients (12.8%) developed clinical hypothyroidism that required thyroid hormone replacement. The median onset time to hypothyroidism was 16 months (range, 3 to 88) and ≥ 60% of patients experienced clinical hypothyroidism within 1 year. By multivariate analysis, background thyroiditis (relative risk [RR], 9.78; p = 0.004), thyroid peroxidase antibody positivity (RR, 9.90; p = 0.003), nodule size (RR, 1.24; p < 0.001), and initial TSH (RR, 1.47; p = 0.009) were the independent risk factors for predicting hypothyroidism in euthyroid patients. CONCLUSION: Hypothyroidism frequently occurs during the follow-up in euthyroid patients with thyroid nodules which show lymphocytic thyroiditis on FNA cytology. Close surveillance and regular TFT are needed in high-risk patients for upcoming clinical hypothyroidism.

Sex differences in risk factors for subclinical hypothyroidism.

OBJECTIVE: To investigate the prevalence of subclinical hypothyroidism (SCH) in Korean adults and identify the risk factors for the occurrence of SCH by sex. DESIGN AND METHODS: This study used data from the Sixth Korea National Health and Nutrition Examination Survey (KNHANES VI), a cross-sectional, nationally representative survey, which comprises a health interview survey, a health examination survey and a nutrition survey. To examine SCH, the reference range of thyroid-stimulating hormone (TSH) was defined using both the range provided by the test kit manufacturer (SCH-M) and a population-based range (SCH-P). We investigated the prevalence of SCH and its risk factors by sex using both reference ranges. RESULTS: The prevalence of SCH in Koreans according to SCH-M (0.35-5.5 µIU/mL) was 5.6%, and 3.3% with SCH-P (0.62-6.68 µIU/mL). For men, smoking significantly reduced the incidence of SCH, positive anti-thyroid peroxidase antibody (TPOAb) significantly increased the risk of SCH, and in an adjusted model, the risk of SCH in all quartiles increased as the urine iodine creatinine ratio (UICR) quartile increased. For women, positive TPOAb was confirmed as a risk factor for SCH, as was the highest UICR quartile. Furthermore, the odds ratio for SCH in urban vs rural residence was 1.78. CONCLUSIONS: The prevalence rates of SCH were similar to those reported in the literature and previously known risk factors were confirmed using both TSH reference ranges. The notable findings from this study are that the increased risk of SCH with increased iodine intake was more marked in men than in women and that residential area may be a risk factor for SCH in women.

Recombinant human TSH stimulated thyroglobulin levels at remnant ablation predict structural incomplete response to treatment in patients with differentiated thyroid cancer.

In patients with differentiated thyroid cancer, stimulated thyroglobulin (sTg) levels after thyroid hormone withdrawal (THW) at remnant ablation (RA) and at 6 to 12 months are known to have good prognostic value. This study aimed to evaluate the prognostic impacts and best cutoff values of sTg levels under recombinant human thyroid stimulating hormone (rhTSH) treatment at RA and at follow-up. A total of 151 patients were enrolled, of whom 77 were followed up with rhTSH-stimulated Tg (rhTSH-sTg) and 74 with THW-stimulated Tg (THW-sTg) at 6 to 12 months after rhTSH-aided RA. Risk stratification, response to treatment (excellent, indeterminate, biochemical incomplete, and structural incomplete response [SIR]), and clinical outcome were accessed by revised American Thyroid Association (ATA) guideline criteria. Seven out of 151 (4.6%) patients were confirmed to have SIR during the median follow-up of 79.0 months; 3 in the rhTSH group and 4 in the THW group. One hundred thirty-two out of 151 (87.4%) patients were confirmed to have excellent response; 68 (51.5%) in the rhTSH group and 64 (48.5%) in the THW group. The cutoff values of sTg for predicting SIR to treatment at rhTSH-aided RA, THW-sTg, and rhTSH-sTg were 4.64 ng/mL (sensitivity 85.7%, specificity 76.4%, negative predictive value [NPV] 99.2%), 2.41 ng/mL (sensitivity 100%, specificity 94.3%, NPV 100%), and 1.02 ng/mL (sensitivity 66.7%, specificity 94.6%, NPV 98.6%), respectively. sTg levels using rhTSH at both RA and follow-up has a high NPV and are as effective as using THW for predicting SIR. The risk classification according to the revised ATA guidelines can be used effectively to supplement rhTSH-aided sTg levels to predict better clinical outcomes.

Prognostic value of preoperative anti-thyroglobulin antibody in differentiated thyroid cancer.

CONTEXT: The coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune disease could represent a better or worse prognosis. This study investigated the prognostic importance of preoperative anti-thyroglobulin antibody (TgAb) in DTC patients. DESIGN AND PATIENTS: This retrospective hospital-cohort study enrolled 1171 consecutive DTC patients with preoperative TgAb data, who underwent total thyroidectomy between January 2006 and December 2011. Clinical parameters studied included demographics, primary tumour characteristics, radioiodine therapy, thyroid function tests, preoperative thyroglobulin (Tg) and TgAb levels, and cancer persistence/recurrence. RESULTS: A total of 254 (21.7%) patients were preoperatively TgAb positive. The percentage positive for thyroid peroxidase (TPO) antibody and lymphocytic thyroiditis was significantly higher in the TgAb-positive group. The TgAb-positive group had a significantly higher rate of lymphatic invasion and lymph node metastasis both overall and in patients without TPOAb and lymphocytic thyroiditis (non-HT group). The mean number of total and central lymph nodes dissected and rate of lateral lymph node dissection were significantly higher in the TgAb-positive group, both overall and in non-HT patients. In regression analysis, preoperative TgAb was an independent risk factor for lateral lymph node metastasis. Over 50.2±14.5 months of follow-up, disease persistence/recurrence was not significantly different between patients with and without TgAb, both overall and in non-HT patients. Preoperative TgAb showed no significant correlation with final disease status. CONCLUSION: Positive preoperative serum TgAb is associated with worse primary tumour characteristics but rarely showed poor prognosis, probably due to more aggressive treatment of these subjects.

Low muscle mass and risk of type 2 diabetes in middle-aged and older adults: findings from the KoGES.

AIMS/HYPOTHESIS: Asians have a propensity to develop type 2 diabetes with a lower BMI than Western populations. This discrepancy may be due to differences in body fat and muscle mass for a given BMI. However, unlike adiposity, it is unclear whether muscle mass affects the risk of type 2 diabetes in Asian populations. METHODS: We conducted a 2-yearly prospective assessment of 6895 participants who were free of diabetes at the baseline examination as part of the Korean Genome Epidemiology Study. The muscle mass index (MMI) was defined as the weight-adjusted appendicular skeletal muscle mass. Using Cox regression models, we evaluated the association between MMI and the risk of developing type 2 diabetes across sex-specific tertiles of MMI. Low muscle mass was defined as the sex-specific lowest tertile of MMI. Main covariates included age, sex, urban or rural residence, family history of diabetes, hypertension, smoking status, education level, monthly income, physical activity, alcohol consumption and diet. In addition, body fat mass, waist circumference and BMI were controlled as categorical variables. Obesity was defined as a BMI of ≥25 kg/m2 or a waist circumference of ≥90 cm for men and ≥85 cm for women. RESULTS: During a median follow-up of 9.06 years, 1336 participants developed type 2 diabetes. At baseline, the mean age was 52.1 years and the mean BMI was 24.4 kg/m2. The mean MMI for men and women was 32.1% and 26.0%, respectively. There was an inverse association between MMI and the risk of type 2 diabetes. Multivariate-adjusted HRs for the risk of developing type 2 diabetes were 2.05 (95% CI 1.73, 2.43), 1.39 (95% CI 1.17, 1.66) and 1.0 from the lowest to highest sex-specific MMI tertile, with an HR of 1.35 (95% CI 1.26, 1.45) per SD decline in MMI. Further adjustments for fat mass, waist circumference and BMI as categorical variables did not modify the relationship (each p < 0.01). In BMI-stratified analyses, the population-attributable fraction of the lowest tertile of MMI for developing type 2 diabetes was increased by 11.9% in the non-obese group and 19.7% in the obese group. CONCLUSIONS/INTERPRETATION: Low muscle mass as defined by MMI was associated with an increased risk of type 2 diabetes, independent of general obesity, in middle-aged and older Korean adults.

Obesity, metabolic health, and mortality in adults: a nationwide population-based study in Korea.

BMI, metabolic health status, and their interactions should be considered for estimating mortality risk; however, the data are controversial and unknown in Asians. We aimed to investigate this issue in Korean population. Total 323175 adults were followed-up for 96 (60-120) (median [5-95%]) months in a nationwide population-based cohort study. Participants were classified as "obese" (O) or "non-obese" (NO) using a BMI cut-off of 25 kg/m(2). People who developed ≥1 metabolic disease component (hypertension, diabetes, dyslipidaemia) in the index year were considered "metabolically unhealthy" (MU), while those with none were considered "metabolically healthy" (MH). The MUNO group had a significantly higher risk of all-cause (hazard ratio, 1.28 [95% CI, 1.21-1.35]) and cardiovascular (1.88 [1.63-2.16]) mortality, whereas the MHO group had a lower mortality risk (all-cause: 0.81 [0.74-0.88]), cardiovascular: 0.73 [0.57-0.95]), compared to the MHNO group. A similar pattern was noted for cancer and other-cause mortality. Metabolically unhealthy status was associated with higher risk of all-cause and cardiovascular mortality regardless of BMI levels, and there was a dose-response relationship between the number of incident metabolic diseases and mortality risk. In conclusion, poor metabolic health status contributed more to mortality than high BMI did, in Korean adults.

Association of serum calcium concentrations with fibrinogen and homocysteine in nondiabetic Korean subjects.

Considerable evidence shows that increased serum calcium levels are associated with metabolic disorders, cardiovascular disease, and increased mortality. This study investigated whether serum calcium, within a normal range, is significantly associated with serum fibrinogen and homocysteine, markers of increased cardiovascular disease risk in nondiabetic Korean subjects.A cross-sectional analysis was performed on 1096 subjects (mean age, 55.1 ±â€Š11.1 years; 36.1% women) undergoing a general health checkup. Serum biochemistry was analyzed including serum albumin-corrected calcium (Cac), insulin resistance (IR, using homeostasis model assessment [HOMA]), fibrinogen, and homocysteine.Compared with patients within the lowest Cac quartile, those with higher Cac levels had increased fibrinogen and homocysteine levels as well as an increased proportion of smoking, dyslipidemia, and HOMA-IR. Correlation analyses revealed linear relationships for Cac with fibrinogen and homocysteine in both genders. After adjustment for confounding factors, serum Cac was significantly associated with high fibrinogen (odds ratio [OR] for the highest vs the lowest quartile = 1.76, 95% confidence interval [CI] = 1.09-2.83, P = 0.02) and homocysteine (OR = 1.83, 95% CI = 1.07-3.11, P = 0.027). Multivariate regression models showed that Cac was linearly associated with fibrinogen (standardized ß = 0.14, P < 0.001) and homocysteine (standardized ß = 0.07, P = 0.009).High normal calcium concentrations were independently associated with increased levels of fibrinogen and homocysteine. Further investigation is needed to validate whether slightly increased calcium levels within the normal range indicate a higher risk of cardiovascular disease.

Relationship between metabolic syndrome and thyroid nodules in healthy Koreans.

BACKGROUND/AIMS: This study evaluated the relationship between thyroid nodules and metabolic syndrome (MS) and its components in apparently healthy Koreans. METHODS: We reviewed the records of 3,298 subjects with no noticeable symptoms who underwent thyroid ultrasound imaging as part of a routine check-up between July 2009 and June 2010; of these, 1,308 were excluded based upon predefined criteria. Among the remaining 1,990 patients, we examined the association between MS and its components and the incidence of thyroid nodules. RESULTS: Of the 1,990 subjects included in this study, 38.4% (n = 764) had thyroid nodules and 12.7% (n = 253) had MS. Female sex, older age, higher body mass index, larger waist circumference, higher glycated hemoglobin level, lower thyroid stimulating hormone level, and presence of MS were all closely related with the presence of thyroid nodules (all p < 0.05). Furthermore, the relevant number of MS components showed a positive linear correlation with the occurrence of thyroid nodules (p < 0.001). Evidence of MS alone was not independently associated with thyroid nodules after adjusting for sex and age in a multivariate binary logistic regression analysis; however, glycated hemoglobin for females and waist circumference for males, as well as both age and thyroid stimulating hormone for all patients, were identified as independent predictors for the existence of thyroid nodules (all p < 0.05). CONCLUSIONS: This study suggests a positive relationship between the components of MS and thyroid nodules in an ostensibly healthy Korean population. Our data support the idea that the recent increase in thyroid nodules is partly due to increases in both MS and obesity.

Ambient Temperature and Prevalence of Obesity: A Nationwide Population-Based Study in Korea.

BACKGROUND: Recent studies have suggested a possible association between outdoor or indoor temperature and obesity. We aimed to examine whether ambient temperature is associated with the prevalence of obesity or abdominal obesity in the Korean population. METHODS: Data on anthropometric, socio-demographic, laboratory and lifestyle factors were retrieved from National Health Insurance System data obtained in 2009-2010. Thirty years (1981 to 2010) of meteorological parameters for 71 observation areas were acquired from the Korea Meteorological Administration. Included in this analysis were 124,354 individuals. A body mass index (BMI) ≥ 25 kg/m2 and a waist circumference (WC) ≥ 90 cm (men) or 85 cm (women) were considered to represent obesity and abdominal obesity, respectively. RESULTS: The mean annual temperature (MAT) ranged from 6.6°C to 16.6°C, and BMI was positively correlated with MAT (r = 0.0078, P = 0.0065). WC was positively correlated with MAT (r = 0.0165, P < 0.0001) and negatively correlated with the number of days with mean temperature < 0°C (DMT0; r = -0.0129, P = 0.0002). After adjusting for age, sex, smoking status, alcohol consumption, exercise, income, residential area and altitude, the odds ratios (95% CI) for obesity and abdominal obesity in the highest quintile MAT group were 1.045 (1.010, 1.081) and 1.082 (1.042, 1.124), respectively, compared with the lower four quintiles of the MAT group. Similarly, subjects in the area of the lowest quintile of DMT0 had significantly higher odds of abdominal obesity compared with the higher four quintile groups of DMT0. CONCLUSION: This study finds an association between ambient temperature and prevalence of obesity in the Korean population when controlling for several confounding factors. Adaptive thermogenesis might be a possible explanation for this phenomenon.

Refractory Graves' Disease Successfully Cured by Adjunctive Cholestyramine and Subsequent Total Thyroidectomy.

The three major forms of treatment for Graves thyrotoxicosis are antithyroid drugs, radioactive iodine therapy and thyroidectomy. Surgery is the definitive treatment for Graves thyrotoxicosis that is generally recommended when other treatments have failed or are contraindicated. Generally, thyrotoxic patients should be euthyroid before surgery to minimize potential complications which usually requires preoperative management with thionamides or inorganic iodine. But several cases of refractory Graves' disease have shown resistance to conventional treatment. Here we report a 40-year-old female patient with Graves' disease who complained of thyrotoxic symptoms for 7 months. Her thyroid function test and thyroid autoantibody profiles were consistent with Graves' disease. One kind of thionamides and ß-blocker were started to control her disease. However, she was resistant to nearly all conventional medical therapies, including ß-blockers, inorganic iodine, and two thionamides. She experienced hepatotoxicity from the thionamides. What was worse is her past history of serious allergic reaction to corticosteroids, which are often used to help control symptoms. A 2-week regimen of high-dose cholestyramine improved her uncontrolled thyrotoxicosis and subsequent thyroidectomy was successfully performed. In conclusion, cholestyramine could be administered as an effective and safe adjunctive agent for preoperative preparation in patients with severe hyperthyroid Graves's disease that is resistant to conventional therapies.

Lowered cutoff of lymph node fine-needle aspiration thyroglobulin in thyroid cancer patients with serum anti-thyroglobulin antibody.

OBJECTIVE: Fine needle aspiration cytology (FNAC) and measurement of thyroglobulin (Tg) in needle washout (FNA-Tg) are recommended for the diagnosis of metastatic or recurrent lymph nodes (LNs) in differentiated thyroid cancer (DTC). However, the effect of serum Tg antibody (TgAb) on FNA-Tg levels still remains unclear in the preoperative setting. We analyze the interference of serum TgAb on FNA-Tg levels as proof of concept in the diagnostic advantage of serum TgAb combined with FNA-Tg. SUBJECTS AND METHODS: A total of 370 suspicious cervical LNs from 273 patients with DTC were included. The primary tumor was confirmed as DTC on preoperative pathology in all patients. We performed FNA-Tg measurement and FNAC on suspicious LNs and evaluated the diagnostic performance of FNAC and FNA-Tg according to TgAb status. Final diagnoses were confirmed by histological examination of excised specimens or by follow-up ultrasonography for at least 6 months. RESULTS: Data from 273 subjects with suspicious 370 LNs were evaluated. Fifty-five LNs (14.9%) were from TgAb+ positive serum TgAb (TgAb+) patients. Serum Tg and FNA-Tg levels were significantly lower in patients with TgAb+ than in those with TgAb-negative (TgAb-). Final pathology confirmed 109 LNs (29.5%) as malignant. Diagnostic performance of FNA-Tg at the same cutoff level was lower in the TgAb+ than TgAb- group. FNA-Tg cutoff levels determined by ROC curve were lower in the TgAb+ group. CONCLUSION: The results suggested that the cutoff value of FNA-Tg should be lowered in suspicious LN before thyroidectomy in thyroid cancer patients with TgAb.

Identification of Intermediate- to High-Risk Papillary Thyroid Carcinoma Patients Who May Be Safely Managed without the Performance of Delayed Stimulated Thyroglobulin Measurements following Total Thyroidectomy and Radioactive Iodine Therapy.

Background. The measurement of stimulated thyroglobulin (sTg) after total thyroidectomy and remnant radioactive iodine (RAI) ablation is the gold standard for monitoring disease status in patients with papillary thyroid carcinomas (PTCs). The aim of this study was to determine whether sTg measurement during follow-up can be avoided in intermediate- and high-risk PTC patients. Methods. A total of 346 patients with PTCs with an intermediate or high risk of recurrence were analysed. All of the patients underwent total thyroidectomy as well as remnant RAI ablation and sTg measurements. Preoperative and postoperative parameters were included in the analysis. Results. Among the preoperative parameters, age below 45 years and preoperative Tg above 19.4 ng/mL were significant risk factors for predicting detectable sTg during follow-up. Among the postoperative parameters, thyroid capsular invasion, lymph node metastasis, and ablative Tg above 2.9 ng/mL were independently correlated with a detectable sTg range. The combination of ablative Tg less than 2.9 ng/mL with pre- and postoperative independent risk factors for detectable sTg increased the negative predictive value for detectable sTg up to 98.5%. Conclusions. Based on pre- and postoperative parameters, a substantial proportion of patients with PTCs in the intermediate- and high-risk classes could avoid aggressive follow-up measures.

Accelerated disease progression after discontinuation of sorafenib in a patient with metastatic papillary thyroid cancer.

Distant metastases from papillary thyroid carcinoma (PTC) are rare and are associated with a poor prognosis. Here, we describe a patient with metastatic PTC who was treated with a tyrosine kinase inhibitor (TKI, sorafenib) for several months that was acutely exacerbated by discontinuation. A 43-year-old male was diagnosed with PTC in February 2004 and underwent total thyroidectomy followed by two courses of high-dose radioactive iodine (RAI) therapy. Despite two additional courses of high-dose RAI therapy, lung and muscle metastases were developed. Treatment with sorafenib was begun in September 2010. After 11 months treatment of sorafenib, newly developed metastatic lesions were found in mediastinal lymph nodes, liver, and bones. Considered as treatment failure, the administration of sorafenib was discontinued. Two weeks after sorafenib treatment was stopped, the disease progressed abruptly and caused death of the patient by respiratory failure. In our patient, PTC progressed rapidly after the cessation of sorafenib treatment. Patients with several other types of cancer have also experienced such rapid disease progression, termed "flare-ups." Physicians should be aware that flare-ups may occur in advanced PTC patients following the cessation of TKI therapy.

Non-FDG-avid primary papillary thyroid carcinoma may not differ from FDG-avid papillary thyroid carcinoma.

BACKGROUND: FDG (2-[(18)F]Fluoro-2-D-deoxyglucose-positron emission tomography (PET)/computed tomography (CT), which can detect a change in glucose metabolism in cancer cells, has been introduced as a diagnostic and prognostic tool in papillary thyroid carcinoma (PTC). However, differences in the clinicopathological and biological characteristics between primary PTCs with FDG uptake and those without FDG uptake are not well established. METHODS: A total of 188 patients with PTC who had preoperative PET/CT scans were enrolled to compare the differences of clinicopathological parameters between FDG-avid (F-PTC; n = 150) and non-FDG-avid tumors (FN-PTC; n = 38). Immunohistochemical staining for glucose transporter (GLUT)-1 and hypoxia-inducible factor-1 alpha (HIF-1α) was performed. RESULTS: FN-PTCs were smaller; had a lower incidence of lymphatic invasion, vascular invasion, multifocality, and central lymph node metastasis; and had a lower maximum standardized uptake value than F-PTCs. After exclusion of high-risk patients for recurrence, FN-PTCs remained smaller (p < 0.001) and had less lymphatic invasion (p = 0.061). Among tumors larger than the spatial resolution of the PET/CT scan, macrocalcification was more frequent in FN-PTC than in F-PTC (p = 0.043). While FN-PTC and F-PTC showed no difference in GLUT-1 expression (50% vs. 75%, p = 0.363), FN-PTC showed lower HIF-1α immunoreactivity than F-PTC (25.0% vs. 75.0%, p = 0.032). CONCLUSION: Tumor size and macrocalcification are clinicopathological differences between FN-PTC and F-PTC. Biologically, HIF-1α may be responsible for increased FDG uptake in PTC.

Natural course of cytologically benign thyroid nodules: observation of ultrasonographic changes.

BACKGROUND: The natural course of cytologically benign thyroid nodules remains unclear. The aim of this study was to evaluate whether ultrasonographic (US) changes are associated with changes in nodule volume during follow-up. METHODS: We retrospectively reviewed over 4 years of clinical records of patients with benign thyroid nodules as confirmed by fine needle aspiration (FNA). In total, 186 patients with 202 benign thyroid nodules were included for study. We assessed for changes in nodule volume and examined the cystic portion of the nodule as well as four US features (echogenicity, margin, calcification pattern, and shape). RESULTS: During follow-up (mean, 21.7±10.7 months) and using 50% as a cutoff value, nodule volumes increased in 11.8%, exhibited no change in 79.9%, and decreased in 8.3% of patients. Proportion of nodules demonstrating at least one US change was 20.8% (42/202). The most common US changes (in descending order of frequency) were cystic change, margin change, and calcification pattern change. Nodule shape and echogenicity rarely changed. Increased nodule volume was not significantly associated with any US features or with the number of FNAs but was associated with younger age at time of diagnosis. CONCLUSION: Although a portion of thyroid nodules confirmed as benign showed US changes or volume changes during the follow-up period, these findings may only represent the natural course of benign nodules. Frequent follow-up with US might be needed for only a small number of cases with suspicious US findings.

Combination of initial stimulation thyroglobulins and staging system by revised ATA guidelines can elaborately discriminate prognosis of patients with differentiated thyroid carcinoma after high-dose remnant ablation.

PURPOSE: The aim of this study was to evaluate prognostic role of thyroglobulin (Tg) levels at the time of ablation (A-Tg) and stimulation Tg levels at 6-12 months after remnant ablation (S-Tg) combined with revised American Thyroid Association (ATA) guidelines risk stratification. PATIENTS AND METHODS: Data of 359 patients (median follow-up duration: 66.3 months) with papillary thyroid carcinoma who had high-dose remnant ablation were analyzed. The cutoff value of A-Tg to predict the persistent/recurrent disease was calculated by receiver operating characteristic curve analysis. In each risk group by ATA guidelines, the association of A-Tg with persistent/recurrent disease was evaluated. The role of A-Tg and ATA risk stratification in each S-Tg group (group with S-Tg <2 ng/mL, 2-10 ng/mL, or >10 ng/mL) was also evaluated. Tg response was determined by the difference between A-Tg and S-Tg with consideration of the dose of radioactive iodine ablation. RESULTS: A-Tg above 5.22 ng/mL was associated with persistent/recurrent disease in all risk groups by ATA guidelines. A-Tg above the cutoff value and ATA risk assessment was related to persistent/recurrent disease in patients with S-Tg 2 to 10 ng/mL (P = 0.003) and S-Tg above 10 ng/mL (P = 0.019). However, no difference in the incidence of persistent/recurrent disease was found according to Tg response. The scoring system made up of A-Tg, S-Tg, and ATA staging showed elaborate discrimination of prognosis. CONCLUSION: Risk stratification using combined scoring with initial stimulated Tg levels, including A-Tg and S-Tg, and staging system by revised ATA guidelines can effectively predict persistent/recurrent disease in patients with papillary thyroid carcinoma.

Absence of galectin-3 immunostaining in fine-needle aspiration cytology specimens from papillary thyroid carcinoma is associated with favorable pathological indices.

BACKGROUND: Galectin-3 (G3) immunostaining of fine-needle aspiration (FNA) samples from thyroid nodules is very useful for the diagnosis of malignancy. The objective of the present study was to determine whether the absence of G3 immunostaining in preoperative FNA samples is associated with favorable clinicopathological parameters, including lymph node (LN) metastasis, in papillary thyroid carcinoma (PTC). METHODS: The records of 868 patients with PTC who had prethyroidectomy ultrasonography-guided FNA with G3 immunostaining between January 2006 and December 2009 were retrospectively reviewed. G3 immunostaining was considered positive if the percentage of tumor cells showing definite cytoplasmic immunostaining exceeded 5%. Patients who had negative G3 immunostaining of FNA samples were assigned to the G3-negative (G3N) group; whereas those who had positive G3 immunostaining were assigned to the G3-positive (G3P) group. RESULTS: There were 92 patients who were assigned to the G3N group (10.6%) because of the negative staining for G3 in the preoperative FNA samples from their thyroid nodules. The proportion of PTC subtypes in the G3N and G3P groups was similar (p=0.376). There was less frequent thyroid capsular invasion (46.7% vs. 66.5%, p<0.001), extrathyroidal extension (28.3% vs. 48.5%, p<0.001), and LN metastasis (22.2% vs. 48.7%, p<0.001) in the G3N group than the G3P group. In multivariate regression analysis, G3N expression predicted a lower risk of LN metastasis (odds ratio=0.37, 95% confidence interval 0.18-0.78) after adjustment for other clinicopathological parameters. Over a median follow-up of 33 months, no association was observed between G3N and disease-free survival. CONCLUSION: The absence of G3 expression in FNA samples from PTC is associated with pathological parameters considered less aggressive than is the case for PTCs with G3 expression, including being a negative predictor of negative LN involvement. Long-term follow-up studies, however, are needed to verify whether G3N patients have lower recurrence and mortality rates.

Evaluation of the effectiveness of sarpogrelate on the surrogate markers for macrovascular complications in patients with type 2 diabetes.

Sarpogrelate, a selective 5-HT(2) receptor antagonist, is known to have a significant effect on antiplatelet action. This study was a double-blinded, randomized, paralleled multicenter trial to compare the effects of sarpogrelate and aspirin on preventing macrovascular complications in patients with type 2 diabetes. The subjects were randomly assigned to either the sarpogrelateor the aspirin group. The baseline parameters for macrovascular complications, such as intima media thickness (IMT), ankle-brachial index (ABI), IL-6, serotonin, adiponectin, and hsCRP, were measured before drug administration. Changes were compared at 6 and 12 months after the administration of each drug. A total of 127 subjects (63 in the sarpogrelate group and 64 in the aspirin group) were pooled during the study period. No significant differences were found in baseline IMT or in other predictors of macrovascular complications. The mean IMT increased in both groups after 12 months, but there was no significant difference between the two groups. No significant change was found in the other predictors of macrovascular complications nor in the incidence of drug-related adverse events between the two groups. During the study period, no significant differences were found between the sarpogrelate group and aspirin group in the clinical indices or in the safety of the subjects related to macrovascular complications. This suggests that sarpogrelate may be clinically useful for the primary prevention of macrovascular complications in patients with type 2 diabetes.

Role of [(18)F]-fluorodeoxy-D-glucose positron emission tomography and computed tomography in the early detection of persistent/recurrent thyroid carcinoma in intermediate-to-high risk patients following initial radioactive iodine ablation therapy.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) scan has a role in the surveillance of patients with a history of thyroid carcinoma. Its efficacy after remnant ablation as far as detecting persistent or recurrent thyroid carcinoma before other surveillance methods is not known, however. In intermediate-to-high risk thyroid carcinoma patients we studied whether PET/CT scan, performed 6-12 months after the first remnant ablation, could provide more information than ultrasonography (US) and thyrotropin-stimulated serum thyroglobulin (Tg) determination with diagnostic whole-body scan (DxWBS). METHODS: We studied 71 subjects with differentiated thyroid cancer (DTC) who were intermediate-to-high risk for persistent/recurrent disease and who had received PET/CT scan, US, and DxWBS simultaneously with stimulated Tg levels 6-12 months after remnant ablation. To evaluate the diagnostic efficacy of PET/CT scan, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated. RESULTS: Ten subjects (14%) had persistent/recurrent disease detected 6-12 months after remnant ablation. Persistence/recurrence was detected in nine (12.7%) of these patients by conventional methods, including US and DxWBS, along with stimulated Tg levels. The remaining case was detected solely by a PET/CT scan, which showed a mediastinal prevascular lesion; this was confirmed by a therapeutic WBS after additional radioiodine therapy. Among the six patients whose PET/CT scan showed positive results, five had persistent/recurrent disease. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of PET/CT scan for detecting persistent/recurrent thyroid carcinoma were 50%, 98.4%, 83.3%, 92.3%, and 91.5%, respectively. CONCLUSION: In intermediate-to-high risk patients with DTC seen 6-12 months after their first remnant ablation, there is almost no complementary role for adding a PET/CT scan to conventional follow-up methods, an US and a DxWBS simultaneously with stimulated Tg levels.

Serum 25-hydroxyvitamin D concentration and arterial stiffness among type 2 diabetes.

AIM: To evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] and arterial stiffness in patients with type 2 diabetes. METHODS: Serum 25(OH)D was measured in a cross-sectional sample of 131 men and 174 women aged 30 years and over in Korea. Arterial stiffness was assessed by pulse wave velocity (PWV) obtained with a VP-2000 pulse wave unit. Fasting plasma glucose, insulin, lipid profile, HbA1c, calcium, phosphorous, and HS-CRP were measured. RESULTS: The prevalence of vitamin D deficiency was high (85.9%). Those with lower vitamin D levels had increased PWV. Using multivariate regression analysis, low 25(OH)D concentrations independently predicted PWV (p<0.001) in people with type 2 diabetes after adjustment for other risk factors such as age, smoking, hypertension, HS-CRP, diabetes duration, hypertension duration, HbA1c, and BMI. CONCLUSIONS: Vitamin D deficiency is common in type 2 diabetes, and a low 25(OH)D level is significantly associated with increased arterial stiffness in these patients. Vitamin D may influence the development of cardiovascular disease. Clinical intervention studies are needed to clarify whether treatment with vitamin D decreases the risk of cardiovascular disease in patients with type 2 diabetes.