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Objective Anaplastic thyroid carcinoma ( ATC) is one of the most aggressive malignancies. Nevertheless, there have been reports that some patients experience long-term survival and those in whom ATCs of small size are often detected. We evaluated the time trend of characteristics of ATC such as size and association with coexistent differentiated thyroid carcinoma ( DTC). We also found the characteristics of patients showing long-term survival. Design and Patients This is a retrospective observational cohort study from the two major tertiary referral hospitals in Seoul, Korea. Ninety-five patients who had been diagnosed with ATC from 1995 to 2010 were included. We classified them into three groups according to the time of initial diagnosis: group 1 (1995-1999), group 2 (2000-2004) and group 3 (2005-2010). Results The mean tumour size decreased significantly according to groups; 6·2, 5·5 and 4·0 cm in group 1, 2 and 3, respectively ( P = 0·02). The frequency of cases with coexistent DTC increased; 10·3%, 35·1% and 48·3% in group 1, 2 and 3, respectively ( P = 0·02). Fifteen of 95 patients survived more than 24 months, and among them, 13 are still alive who underwent curative surgery. Among 15 long-term survivors, nine patients with ATC arising from DTC had ATC tumour portion less than 1 cm. Another five patients with ATC without coexistent DTC had relatively small-sized tumours (1·0-4·0 cm). Conclusion The tumour size of ATC decreased, and cases with coexistent DTC increased over the last two decades. We found that patients with ATC showing long-term survival are those who had atypical presentations such as anaplastic transformation in early stage of DTC or small size of tumours without coexistent DTC. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate differences in serum thyroid-stimulating hormone (TSH) levels according to smoking status and urine iodine concentration (UIC) in a healthy Korean population using data from the Sixth Korean National Health and Nutrition Examination Survey (KNHANES VI)., Study Design: Sixth Korean National Health and Nutrition Examination Survey (2013-2015) is a nationwide, cross-sectional survey of the Korean population., Patients: Research subjects were selected by two-stage stratified cluster sampling of the population and housing census data. A total of 5639 subjects aged >18 years, who were not pregnant, and had undergone thyroid function testing during the survey period, were included., Measurement: The level of serum TSH according to smoking status, iodine intake and presence of TPOAb were evaluated., Results: In the reference population, mean serum TSH level in current smokers (1.87 mIU/L, 95% CI, 0.52-5.37 mIU/L) was significantly lower than that in nonsmokers (2.33 mIU/L, 95% CI, 0.79-6.69 mIU/L, P < .001). The rate of thyroperoxidase antibody (TPOAb) positivity was higher in never smoker (7.7%) than past smokers (5.1%) and current smokers (4.7%), but sex-specific rate of TPOAb was not different according to smoking status. The lower serum TSH levels in current smokers were more apparent in iodine-deficient subjects (UIC < 100 μg/L), and this change was diminished in subjects with UICs between 100 and 299 μg/L. The difference in serum TSH levels in current smokers disappeared in subjects with UICs ≥ 300 μg/L., Conclusions: Smoking is associated with a left-shift in serum TSH level that is more apparent in iodine-deficient subjects. Smoking status is not associated with the presence of TPOAb or iodine intake. The results suggest that smoking has a direct effect on thyroid function that is not mediated by autoimmune processes in the thyroid gland., (© 2018 John Wiley & Sons Ltd.)

Primary thyroid lymphoma is a very rare tumor and its prevalence is approximately 0.1% of all thyroid cancers in Korea. Its clinical experience is limited and not familiar to physicians. Therefore, we performed this study to investigate the clinical characteristics of primary thyroid lymphoma in Koreans. We retrospectively analyzed the medical records of the 44 patients with primary thyroid lymphoma from 1991 to 2006 at four major referral hospitals in Korea. Out of 44 patients, eight patients were male and 36 patients were female and their average age was 57 years. Fifty-six percent of patients had underlying Hashimoto's thyroiditis. All but two patients had non-Hodgkin's lymphoma with B cell origin, and eighty percent of patients presented with stage IE or IIE. Twenty-one of 44 patients (48%) had diffuse large B cell lymphoma (DLBCL) and 17 (39%) had MALT lymphoma. Malignancies originating from lymphoid cells were suspected in 10 of eighteen patients with DLBCL (56%) by using fine-needle aspiration cytology (FNAC), and no difference was noted compared with MALT lymphoma (64%). Compared with DLBCL, the patients with MALT lymphoma were more frequently presented with stage I disease (DLBCL vs. MALT lymphoma: 32% vs. 65%, P=0.04). Moreover, in contrast to DLBCL, most of the patients with MALT lymphoma achieved complete response with treatments (DLBCL vs. MALT lymphoma: 53% vs. 94%, P<0.01). Because of the low diagnostic accuracy of FNAC, thyroid biopsy should be considered for the diagnosis of thyroid lymphomas in suspicious cases. The patients with MALT lymphoma were more frequently presented with early stage diseases and this might lead to the favorable outcome to treatments than those with DLBCL.

Background: Anaplastic thyroid carcinoma (ATC), although rare, is one of the most aggressive human cancers, and patients with ATC have extremely poor prognoses despite various therapeutic measures. We wished to determine the prognostic factors of survival and effect of treatment on survival rate in patients with ATC., Methods: We retrospectively reviewed the medical records of the 121 patients (41 men and 80 women) diagnosed with ATC from January 1995 to June 2004 at 5 major referral centers in Korea., Results: Mean patient age at diagnosis was 64 +/- 11 years (range, 17-84 years). Of the 121 patients, 11 (9%) had intrathyroidal tumors, 69 (57%) had extrathyroidal tumors or lymph node involvement, 29 (24%) had distant metastases, and 12 had no data about staging (9%). The mean tumor diameter was 5.5 +/- 2.5 cm (range, 0.5-17.0 cm). At a median follow-up of 41 months (range, 26-122 months), 8 patients were alive. Median survival time was 5.1 months. The disease-specific survival rates were 42% at 6 months, 16% at 12 months, and 9% at 24 months. Sixteen patients (13%) received only supportive care, 25 (21%) received surgery alone, 20 (16%) received radiation treatment or chemotherapy without surgery, and 60 (50%) received surgery plus radiation treatment or chemotherapy. Multivariate analysis showed that age less than 60 years, tumor size less than 7 cm, and lesser extent of disease were independent predictors of lower disease-specific mortality., Conclusions: Long-term survival is possible for ATC patients less than 60 years old and with small localized tumors. Although aggressive multimodal therapy, including surgery, radiation treatment, and chemotherapy, was not significantly associated with improved survival, we advocate aggressive multimodal therapy in selected ATC patients with good prognostic factors.

Background: The BRAF(V600E) mutation, the most common genetic alteration reported in papillary thyroid carcinoma, has been associated with poor prognostic factors., Aim: To determine whether the presence of the BRAF(V600E) mutation is associated with poor prognosis in Korean patients with conventional papillary thyroid microcarcinoma (micro-PTC)., Patients and Methods: DNA was extracted from paraffin-embedded thyroid tumour specimens taken from 60 patients with conventional micro-PTC, as well as from nine patients with follicular variant papillary carcinoma, six with nodular hyperplasia, four with follicular carcinoma (including one with Hürthle cell carcinoma), four with follicular adenoma (including two with Hürthle cell adenoma) and one each with medullary carcinoma, poorly differentiated carcinoma and anaplastic carcinoma. The presence of the BRAF(V600E) mutation was determined by polymerase chain reaction (PCR) amplification of exon 15 followed by direct sequencing., Results: The BRAF(V600E) mutation was detected in tumour samples from 31 of 60 conventional micro-PTC patients (52%), but was not detected in patients with other types of thyroid tumours. The age distribution, tumour size, extrathyroid extension, multifocality and staging did not differ significantly between patients with and without the BRAF(V600E) mutation., Conclusion: In Korean patients with conventional micro-PTC, the presence of the BRAF(V600E) mutation was not significantly associated with prognostic factors.

Graves disease (GD) is an autoimmune thyroid disease and is associated with human leukocyte antigen (HLA)-DR3 and DQA1*0501 in Caucasians. However, the association of HLA with GD is less clear-cut in East Asian populations. We analyzed HLA-DRB1 and -DQB1 associations with GD in 198 Korean patients compared with 200 healthy controls. HLA-DRB1*0803 (27.8% vs. 14.5% in controls, OR = 2.27, corrected p [p(c)] = 0.03) and *1602 (5.1% vs. 0%, OR = 22.34, p(c) = 0.03) alleles and closely linked haplotypes, DRB1*0803-DQB1*0601 and DRB1*1602-DQB1*0502, conferred susceptibility to GD in Koreans. Weak association of DRB1*0301 with GD susceptibility was observed in male patients only (12.5% vs. 3.5%, OR = 3.57, p < 0.05). HLA-DRB1*0101, *0701, *1202, and *1302 alleles were weakly associated with resistance to the disease (OR < 0.5, p < 0.05). Some HLA alleles were weakly associated with clinical characteristics in GD patients. Patients with DRB1*1301-DQB1*0603 developed their diseases in younger ages and were more frequently associated with larger goiter (p < 0.05). Although HLA class II alleles associated with GD in Koreans were different from those in Caucasians, some associations are shared, such as association of DRB1*0301 in male patients and protective effect of DRB1*0701 to GD susceptibility.

Background: Thyrotoxic periodic paralysis (TPP) occurs most frequently in Asian males and present with an acute episode of proximal muscle weakness in the setting of thyrotoxicosis. Despite the fact that mutations were described in genes encoding ion channels in familial hypokalaemic periodic paralysis, no definite genetic variants were found in TPP. beta2-adrenergic receptors (ADRB2s) are expressed in skeletal muscle and stimulate the sodium pump. Single nucleotide polymorphisms in ADRB2 gene were identified and may act as disease modifiers in various diseases., Objective: We were to demonstrate that ADRB2 gene might be a susceptibility gene for TPP in Korean male patients with Graves' disease., Design and Patients: In a series of 28 male TPP patients and 31 control patients, three polymorphisms in ADRB2 gene have been studied: a T to C substitution at -47 (-47T/C), Arg16Gly and Gln27Glu. Control patients were male Graves' patients without history of paralysis., Results: The distributions of the -47C, Gly16 and Glu27 alleles in all patients were 0.02, 0.34 and 0.02, respectively. The genotype Arg16/Arg16 was not significantly associated with TPP (odds ratio 0.53; 95% confidence interval, 0.19-1.50; corrected P = 0.897). Also, the frequency of genotype Gly16/Gly16 was not significantly different in TPP patients than in controls (0.07 vs. 0.23; odds ratio, 0.26; 95% confidence interval, 0.05-1.40; corrected P = 0.45). Allele frequencies of ADRB2 in patients with TPP did not differ from controls., Conclusions: The polymorphism of the ADRB2 gene may not confer genetic susceptibility to TPP in Korean male patients with Graves' disease.

The genetic loci conferring susceptibility to Graves' disease remain unclear. The aim of the present study was to examine a C/T polymorphism in the 5'-untranslated region of the CD40 gene and its relationship with autoimmune thyroid diseases in Koreans. The C/T polymorphism in the 5'-untranslated region of CD40 gene, clinical characteristics, and thyroid antibodies were analyzed in a series of Korean patients (132 with Graves' disease, 118 with Hashimoto's thyroiditis, and 164 normal controls). The CC genotype was significantly associated with Graves' disease (odds ratio, 1.93; 95% confidence interval, 1.21-3.09; corrected p = 0.019). On the other hand, the frequency of the TT genotype was significantly lower in Graves' patients than in controls (8% vs. 18%; odds ratio, 0.38; 95% confidence interval, 0.18-0.82; corrected p = 0.044). Allele frequencies in CD40 did not differ from controls in patients with Hashimoto's thyroiditis. In patients with Graves' disease, there were significant differences between genotypic groups in the activity of stimulating thyrotropin (TSH) receptor antibody. However, clinical characteristics and other thyroid antibodies were not significantly different. In conclusion, the C allele in the 5'-untranslated region of the CD40 gene may confer genetic susceptibility to Graves' disease in Koreans.