Oxidative stress results from either overproduction of free radicals or insufficiency of several anti-oxidant defense systems. It leads to oxidation of main cellular macromolecules and a resultant molecular dysfunction. Thyroid hormones regulate oxidative metabolism and, thus, play a role in free radical production. Studies evaluating oxidative stress in patients with hypothyroidism and hyperthyroidism have been encountered in recent years; however, oxidative status in patients with euthyroid autoimmune thyroiditis (AIT) was not investigated previously. Thirty-five subjects with euthyroid AIT and 35 healthy controls were enrolled in the study. Serum oxidative status was determined by the measurement of total anti-oxidant status (TAS), total oxidant status (TOS), ischemia-modified albumin (IMA), and oxidized-low density lipoprotein (ox-LDL) levels. Serum TAS levels were significantly lower (p<0.001), while serum TOS levels and IMA levels were significantly higher (p<0.001 and p=0.020, respectively) in patients compared to controls. In both groups, ox-LDL levels were similar (p=0.608). Serum TAS levels were negatively correlated with anti-thyroid peroxidase and anti-thyroglobulin (anti-TG) levels (rho=-0.415, p=0.001 and rho=-0.484, p<0.001, respectively). Serum TOS was positively correlated with anti-TG levels (rho=0.547, p<0.001). Further, TAS was positively correlated with free T4 levels (r=0.279, p=0.043). No correlation was observed between thyrotropin, free T3 levels, and TOS and TAS levels. These results suggest that oxidants are increased, and anti-oxidants are decreased in patients with euthyroid AIT, and oxidative/anti-oxidative balance is shifted to the oxidative side. Increased oxidative stress might have a role in thyroid autoimmunity.

It is well known that TSH plays a major role in the secretion of thyroid hormones, maintenance of thyroid specific gene expression, and gland growth. In this study, we aimed to evaluate association between tests of thyroid functions (fT3, fT4, TSH) and differentiated thyroid carcinoma. 441 patients operated for nodular goiter between 2005 and 2008 were analyzed. Thyroid functions were studied in the period of 1-30 days prior to surgery. In postoperative histopathological examination, differentiated thyroid carcinoma and benign thyroid disease were detected in 166 (37.6%) and 275 (62.4%) patients, respectively. Patients with thyroid malignancy had significantly lower serum fT3 (P = 0.001), lower fT4 (P = 0.022), and higher TSH levels (P < 0.001) compared to patients with benign disease, although all analytes were within the normal range. We subdivided by quartile serum fT3, fT4, and TSH in normal limits into three groups. The odds ratio (ORs) for the risk of thyroid cancer with a serum TSH between 0.63 and 1.67 μIU/ml and 1.68-4.00 μIU/ml, compared with a serum TSH between 0.40 and 0.62 μIU/ml were calculated as 2.60 (95% CIs 1.49-4.54) and 6.50 (95% CIs 3.51-12.03), respectively. There was also a greater risk of thyroid cancer in patients with fT3 levels of 1.57-3.00 pg/ml, compared with patients with fT3 levels of 3.89-4.71 pg/ml (OR 2.95, 95% CIs 1.68-5.20). For fT4, OR for the risk of thyroid cancer between 0.85 and 1.17 ng/dl compared with 1.48-1.78 ng/dl was 2.14 (95% CIs 1.22-3.74). In conclusion, lower fT3, fT4, and higher TSH concentrations within normal limits were related with increased thyroid cancer independent from sex and nodule type. Particularly, the association between lower fT3, fT4 levels and a diagnosis of thyroid cancer is a novel finding.

The Bethesda classification is a reliable indicator of malignancy in nodules with different cytology results and seems to be very effective in predicting the malignancy for the nodules diagnosed with aggressive variant PTC on the final histological examination.

Tumor multifocality is not an unusual finding in papillary thyroid carcinoma (PTC), but its clinical significance is controversial. In this study, we aimed to evaluate impact of multifocality, tumor number, and total tumor diameter on clinicopathological features of PTC. Medical records of 912 patients who underwent thyroidectomy and diagnosed with PTC were reviewed retrospectively. Patients were grouped into four according to number of tumoral foci: N1 (1 focus), N2 (2 foci), N3 (3 foci), and N4 (≥4 foci). The diameter of the largest tumor was considered the primary tumor diameter (PTD), and total tumor diameter (TTD) was calculated as the sum of the maximal diameter of each lesion in multicentric tumors. Patients were further classified into subgroups according to PTD and TTD. Multifocal PTC was found in 308 (33.8 %) patients. Capsular invasion, extrathyroidal extension, and lymph node metastasis were significantly higher in patients with multifocal tumors compared to patients with unifocal PTC. As the number of tumor increased, extrathyroidal extension and lymph node metastasis also increased (p = 0.034 and p = 0.004, respectively). The risk of lymph node metastasis was 2.287 (OR = 2.287, p = 0.036) times higher in N3 and 3.449 (OR = 3.449, p = 0.001) times higher in N4 compared to N1. Capsular invasion, extrathyroidal extension, and lymph node metastasis were significantly higher in multifocal patients with PTD ≤10 mm and TTD >10 mm than unifocal patients with tumor diameter ≤10 mm (p < 0.001, p < 0.001 and p = 0.001, respectively). There was no significant difference in terms of these parameters in multifocal patients with PTD ≤10 mm and TTD >10 mm and unifocal patients with tumor diameter >10 mm. In this study, increased tumor number was associated with higher rates of capsular invasion, extrathyroidal extension, and lymph node metastasis. In a patient with multifocal papillary microcarcinoma, TTD >10 mm confers a similar risk of aggressive histopathological behavior with unifocal PTC greater than 10 mm.

TIRADS seems to be useful in predicting malignancy and planning further management in the AUS subcategory, but not quite so in the FLUS subcategory.

Recently, it has been suggested that thyrotropin (TSH) concentration can be used as a marker for prediction of thyroid malignancy. In this study, we aimed to investigate the association between TSH levels and prediction of malignancy in euthyroid patients with different Bethesda categories. The data of 1433 euthyroid patients with 3206 thyroid nodules who underwent thyroidectomy were screened retrospectively. The preoperative cytology results, thyroid function tests, thyroid autoantibodies, and presence of histopathological Hashimoto's thyroiditis (HT) were recorded. Of the 1433 patients, 585 (40.8 %) had malignant and 848 (59.2 %) had benign histopathology. Malignant group had smaller nodule size, elevated TSH levels, and higher rate of presence of HT compared to benign group (p < 0.001, all). Cytology results of 3206 nodules were as follows: 832 nondiagnostic (ND), 1666 benign, 392 atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 68 follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 133 suspicious for malignancy (SM), and 115 malignant. Both SM and malignant cytology groups had higher TSH levels than other 4 Bethesda categories (p < 0.05, all). Benign cytology group had significantly lower TSH levels compared to other cytology groups (p < 0.05, all). Patients with malignant final histopathology in ND and AUS/FLUS cytology groups had significantly higher TSH levels compared to patients with benign final histopathology (p < 0.05, all). Moreover, TSH levels showed to increase from Bethesda categories II to VI. In addition to cytology, higher TSH levels can be used as a supplementary marker in prediction of malignancy in certain Bethesda categories.

The predictors of malignancy are important for the decision of appropriate management in nodules with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). Our aim was to determine the ultrasonographical, clinical, and biochemical predictors of malignancy in these patients. A total of 427 patients with cytologically Bethesda Category III (AUS/FLUS) thyroid nodules were included in this retrospective study. We divided the nodules into two subgroups according to the histopathology as benign and malignant, and compared the preoperative ultrasonographical, clinical, and biochemical findings. In overall, 427 patients with 449 AUS/FLUS nodules who had undergone surgery, the rate of malignancy was 23.4 % (105/449). When evaluated separately, the rate of malignancy was 25.8 % in nodules with AUS (82/318) and 17.6 % in nodules with FLUS (23/131) (p = 0.061). The vast majority of malignant specimens in histopathology consisted of papillary thyroid carcinoma (PTC) (n = 91, 86.7 %). Preoperative ultrasonographic features of 105 malignant nodules in histopathology were compared with the 344 benign nodules in histopathology. Anteroposterior/Transverse (AP/T) ratio was significantly higher in malignant group compared to benign group (p = 0.013). In multiple logistic analysis, we found that higher AP/T ratio and microcalcification were independently associated with malignancy (p < 0.05). The malignancy-associated cut-off value of AP/T ratio at maximum sensitivity and specificity was ≥0.81. We did not find any correlation between malignancy and Hashimoto's thyroiditis in histopathology in multivariate analysis (p > 0.05). In Bethesda Category III nodules with higher AP/T ratio and microcalcification, surgery might be considered as a first therapeutic option instead of repeat fine-needle aspiration biopsy or observation.

The association between papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) is controversial. In this study, we aimed to compare preoperative thyroid functions, ultrasonography (US) features, fine-needle aspiration biopsy (FNAB) results, and histopathological characteristics of PTC in patients with and without HT. Data of 919 PTC patients were reviewed retrospectively. The diagnosis of HT was based on histopathological examination and patients were grouped as HT and non-HT. There were 1321 PTC lesions in 919 patients among which 317 (34.5 %) had coexistent HT. There were no significant differences in nodule volume, longitudinal diameter, texture, echogenicity, marginal regularity, presence of microcalcification and hypoechoic halo, and peripheral vascularization in patients with and without HT (p > 0.05, for all parameters). Macrocalcification was observed more frequently in the non-HT group (p = 0.021). FNAB results were similar in the two groups (p = 0.105). Distribution of variants, capsule invasion, vascular invasion, and extrathyroidal extension were observed with similar rates in the HT and non-HT groups. Lymph node metastasis was significantly higher in patients without HT (p = 0.012). Of the carcinomas, 66.1 % (n = 874) were papillary thyroid microcarcinoma (PTMC). Tumor size was lower in PTMC lesions coexistent with HT (p = 0.026). We observed lower rates of capsule invasion, extrathyroidal extension, and lymph node metastases in PTMC with HT compared to without HT (p = 0.007, p = 0.003, and p = 0.015, respectively). This study showed that US features, FNAB results, and histopathological findings of PTC lesions are not influenced by the presence of HT. However, PTMC seems to be related with less aggressive histopathological behavior in HT.