Kam Tsun Tang

The accuracy of fine-needle aspiration biopsy and frozen section in patients with thyroid cancer.

A total of 1076 patients with thyroid nodules were reviewed. The accuracy of fine needle aspiration biopsy (FNAB) and frozen section (FS) were compared and clinical risk factors were analyzed. Our results indicate that 67.9% are benign and 32.1% are malignant with the predominance of papillary thyroid cancer (75.1%). Overall diagnostic accuracy for FNAB and FS were 90.8%-91.2% and 89.1%-90.5%, respectively. There were no significant differences between the diagnostic accuracy on FNAB and FS in all tumors except the follicular adenoma and carcinoma. The diagnostic accuracy of FS was higher than FNAB in patients with follicular adenoma (89.3% vs. 58.9%, p < 0.001) and but lower than FNAB in patients with follicular carcinoma (46.2% vs. 92.3%, p < 0.001). In conclusion, FNAB is cost effective in the preoperative evaluation of thyroid nodule. FS could be eliminated in most cases except with follicular and Hürthle cell neoplasms. FS is valuable when result of FNAB is suspicious or unavailable. FS is more appropriate in deciding the extent of thyroidectomy in follicular neoplasm and FNAB is more reliable initial approach to surgery in patients with Hürthle cell neoplasm. Clinical risk factors may help in selecting patients for surgery but cannot exceed FS in deciding the extent of thyroidectomy in patients with follicular and Hürthle cell neoplasms.

Cardiovascular autonomic neuropathy, autonomic symptoms and diabetic complications in 674 type 2 diabetes

AIMS To determine the relationships between cardiovascular autonomic neuropathy (CAN) and autonomic symptoms, clinical parameters and diabetic complications in type 2 diabetes (T2DM). METHODS The results of autonomic symptoms, clinical parameters, diabetes complications and cardiovascular reflex (CVR) tests of 674 T2DM were analyzed. RESULTS Significant correlations were found between CAN risk and age (p=0.019), duration of diabetes (p=0.008), HbA1c (p<0.001), systolic blood pressure (p=0.006), nephropathy (p<0.001), retinopathy (p<0.001), and QTc interval (p<0.001), but not BMI and hyperlipidemia. Patients with retinopathy or proteinuria had increase risk of CAN, and proliferative diabetic retinopathy (PDR) was the most significant risk factor (odds ratio: 6.85; 95% CI: 2.32-20.20) for CAN. Eighty-three percent of patients complained of autonomic symptoms; and the more symptoms complained, the higher the prevalence of CAN. Impotence was the only single symptom associated with CAN risk. Additional CAN risks were also observed when patients with multiple symptoms and/or complications in combinations. CONCLUSIONS Our results implied that patients with multiple symptoms and/or complications in combinations have increased CAN risk, and this may provide additional information for clinicians to identify T2DM at risk of having CAN.

Clinical Manifestations and Gene Expression in Patients with Conventional Papillary Thyroid Carcinoma Carrying the BRAFV600E Mutation and BRAF Pseudogene

BACKGROUND The association of BRAF(V600E) with the clinical manifestations of papillary thyroid carcinoma (PTC) remains controversial. Recent studies have shown that the BRAF pseudogene can activate the MAPK pathway and induce tumorigenesis. This study investigated the association of BRAF(V600E), the BRAF pseudogene, and their mRNA levels with clinical features and thyroid-specific gene expression in conventional PTCs. MATERIALS AND METHODS A total of 78 specimens were collected from patients with conventional PTCs. RNA was isolated, and quantitative polymerase chain reaction was used to measure the mRNA levels of BRAF, the BRAF pseudogene, and thyroid-specific and tumor-related genes. Immunohistochemical (IHC) staining of BRAF, ERK, sodium-iodide symporter (NIS), thyrotropin receptor, glucose transporter 1, and Ki67 was also performed. RESULTS BRAF(V600E) and the BRAF pseudogene were detected in 73.0% (57/78) and 91.7% (44/48), respectively, of the conventional PTCs. The presence of BRAF(V600E) was not associated with the multiple clinical features assessed or the recurrence rate during 76.9 ± 47.2 months of follow-up. Neither was it associated with IHC staining or tumor-related/thyroid-specific gene expression, except for decreased NIS gene expression. The BRAF pseudogene was not associated with clinical characteristics or thyroid-specific gene expression, except for decreased decoy receptor 3 (DCR3) expression. High BRAF mRNA levels were associated with bilateral and multifocal lesions, and BRAF-pseudogene mRNA levels were positively correlated with BRAF mRNA levels (r = 0.415, p = 0.009). CONCLUSION These results do not support the use of the BRAF(V600E) mutation as a prognostic marker of conventional PTC. However, the association of high BRAF mRNA levels with more advanced clinical features suggests that BRAF mRNA levels might be a more useful clinical marker of PTCs, independent of the BRAF(V600E) mutation status. The correlation between BRAF-pseudogene mRNA levels and BRAF mRNA levels in PTCs is in agreement with the hypothesis that the BRAF pseudogene regulates BRAF expression during tumorigenesis by acting as competitive noncoding RNA. However, additional studies with larger sample sizes are required to confirm these findings.

Diffuse sclerosing variant of papillary thyroid carcinoma with multiple metastases and elevated serum carcinoembryonic antigen level.

BACKGROUND Diffuse sclerosing variant of papillary thyroid carcinoma (DSPC) is a rare variant of papillary thyroid carcinoma (PTC). We report a 61-year-old female of DSPC whose course was complicated by multiple metastases and an elevated serum carcinoembryonic antigen (CEA) level. SUMMARY The patient presented with upper back pain. X-ray showed an osteolytic lesion of the sixth cervical spinous process. She had a hard, nonmovable mass with fixed enlarged lymph nodes (LNs) over right neck. Fine-needle aspiration cytology revealed PTC with LNs metastasis. Positron emission tomography demonstrated multiple brain, bone, liver, and lung metastases. However, the patient had an elevated serum CEA level. She underwent a total thyroidectomy and 200 mCi radioactive (131)I therapy. The pathological findings were diffuse sclerosing variant of PTC with capsular and lymph vessel invasion. A double staining of tumor specimen appeared concomitantly positive for CEA and thyroglobulin. CONCLUSIONS To our knowledge, DSPC with an elevated CEA level is extremely rare.

Analysis of Associations of Human BAFF Gene Polymorphisms with Autoimmune Thyroid Diseases

Background The B-lymphocyte-activating factor (BAFF) is associated with B-cell functions, and gene polymorphisms of the BAFF have been linked to autoimmune diseases (AIDs). In this study, we explored possible associations of two BAFF single-nucleotide polymorphisms (SNPs), rs1041569 and rs2893321, with autoimmune thyroid diseases (AITDs) in an ethnic Chinese population. Material and Methods In total, 319 Graves’ disease (GD), 83 Hashimoto’s thyroiditis (HT) patients, and 369 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism and direct sequencing were used to genotype rs2893321 and rs1041569. Results There was a significant difference in frequencies of the G allele and AG+GG genotype of rs2893321 between the GD and control groups (p = 0.013, odds ratio (OR) = 0.76, and p = 0.017, OR = 0.68, respectively) and between the AITD and control groups (p = 0.009, OR = 0.76, and, p = 0.014, OR = 0.69, respectively). The AA genotype of rs2893321 was associated with low titers of the thyroid-stimulating hormone receptor antibody (TSHRAb) (p = 0.015) in males but not in females. The AA genotype of rs2893321 was associated with the presence of two different types of thyroid autoantibody (TAb) (TSHRAb and Hashimoto’s autoantibody (anti-thyroglobulin or anti-microsomal antibody)) in females and with that of one type in males. Conclusions rs2893321 may be a susceptible genetic variant for the development of GD and AITDs. Associations of rs2893321 with susceptibility to GD and AITDs and the correlation between rs2893321 and TAb exhibit a dimorphic pattern. Additional studies with larger sample sizes are required to confirm our findings.

Association of IRF8 gene polymorphisms with autoimmune thyroid disease.

The occurrence of autoimmune thyroid disease (AITD) is known to have a major adverse effect on interferon (INF)‐α treatment. The genetic variant of the INF regulatory factor 8 (IRF8), a type 1 INF regulator, is associated with susceptibility to systemic lupus erythematosus and multiple sclerosis. In this study, we investigated possible associations of the IRF8 polymorphisms, rs17445836 and rs2280381, with AITD in an ethnic Chinese population.

Associations of melatonin receptor gene polymorphisms with Graves' disease

Background Melatonin plays an important role in immunity and has been linked to autoimmune diseases. Possible associations of single-nucleotide polymorphisms (SNPs) of melatonin receptor type 1A (MTNR1A) and 1B (MTNR1B), with autoimmune thyroid disease in an ethnic Chinese (i.e., Taiwanese) population were examined. Materials and methods Totally, 83 Hashimoto’s thyroiditis patients, 319 Graves’ disease (GD), and 369 controls were recruited. Three SNPs (rs6553010, rs13140012, and rs2119882) of MTNR1A and three SNPs (rs1387153, rs10830963, and rs1562444) of MTNR1B were genotyped. Results There were a reduced frequency of the C allele of rs2119882 and a reduced percentage of the CC+CT genotype in the GD group compared to the control group (p = 0.039, odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.63~0.99, and p = 0.032, OR = 0.72, 95% CI = 0.53~0.97, respectively). There was a significant difference in the percentage of the AT haplotype of the combination of rs13140012 and rs2119882 between the GD and control groups (p = 0.010, OR = 1.34, 95% CI = 1.07~1.67). In addition, there were significant associations of anti-thyroid peroxidase antibody titers with rs13140012 and rs2119882, and the AATT genotype of the combination of rs13140012 and rs2119882 (p = 0.003, 0.003, and 0.004, respectively). There were no significant associations of SNPs and possible haplotypes of MTNR1B with susceptibility to GD. Conclusions Genetic variants of rs2119882 of MTNR1A and the AT haplotype of the combination of rs2119882 and rs13140012 were associated with GD susceptibility in an ethnic Chinese population. The results support the involvement of the melatonin pathway in the pathogenesis of GD.