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Objective: Some authors have found little or no diagnostic benefit from repeated biopsy of benign thyroid nodules. However, to our knowledge, integration of Thyroid Imaging Reporting and Data System (TIRADS) guidelines with one biopsy for sufficient benign thyroid nodule diagnosis has not been previously described. We investigated malignancy rate and probability by using various malignancy stratification systems in initially biopsy-proven benign nodules and sought to determine their clinical relevance in management of benign thyroid nodules.Methods: This retrospective study collected 6762 thyroid nodules from 6493 consecutive patients who underwent biopsy between January 2013 and December 2013. The initial biopsy with ≥1 year of follow-up was used as the gold standard for benign diagnosis. For our study purpose, we analyzed 2747 (57.0%, 2747 of 4822, 532 women, 2111 men; 229 malignant and 2518 benign) thyroid nodules diagnosed by initial biopsy with 28.2 ± 9.1 (range, 12-41) months of follow-up. We calculated the malignancy probability of thyroid nodules by using various malignancy risk stratification systems.Results: The overall calculated thyroid malignancy rate was 8.3% (229 of 2747). Initially biopsy-proven benign nodules exhibited a ≤3.0% malignancy probability when assessed as "low suspicion" by Korean-TIRADS (K-TIRADS), "low suspicion" by the ATA guideline, and "very probably benign" by the French TIRADS guideline and gave a score of ≤3 by the web-based TIRADS.Conclusion: When initially biopsy-proven benign nodules exhibit a "low suspicion" US pattern and low malignancy probability, as stratified by various TIRADS guidelines, imaging surveillance instead of second biopsy is warranted.Key Points: • One biopsy is sufficient for initially biopsy-proven benign nodules. • Repetitive biopsy is necessary for imaging-pathology mismatched nodules. • Scoring risk stratification permits personalized management. [ABSTRACT FROM AUTHOR]

Background: Active surveillance has been introduced as a management option for low-risk papillary thyroid microcarcinoma (PTMC) due to its mostly indolent course. Methods: This was a multicenter study of 370 PTMC patients who underwent active surveillance more than one year. The changes in volume and maximum diameter between initial and last ultrasonography were evaluated to identify the natural course of PTMC during active surveillance. Results: Patients' age at diagnosis was 51 ± 12 years, and 110 (30%) patients were <45 years of age. The initial maximum diameter and volume of PTMCs were 5.9 ± 1.7 mm and 81.0 ± 77.7 mm3, respectively. During the median 32.5 months of follow-up, 86 (23.2%) patients were found to have an increase in tumor volume, and 13 (3.5%) patients showed an increase in the maximal diameter of the tumor. The cumulative incidence of volume increase gradually rose with time (6.9%, 17.3%, 28.2%, and 36.2% after two, three, four, and five years, respectively). The risk of volume increase in patients <45 years of age was twice as high as in older patients (p = 0.002). There was no significant difference in tumor size change according to sex, levothyroxine treatment, or presence of Hashimoto's thyroiditis. During the period, 58 (15.7%) patients underwent delayed thyroid surgery due to anxiety (37.9%), tumor size increase (32.8%), or appearance of cervical lymph node metastasis (8.6%). Lymph node metastasis was found in 29.3% of patients on pathological examination. Conclusions: A significant number of PTMCs grow during active surveillance, and tumor volume change is a more sensitive means of evaluating tumor growth. Active surveillance can be carefully applied for selected patients. Although it is not contraindicated, it should be applied more cautiously for younger patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: The purpose of this study was to construct a web‐based predictive model using ultrasound characteristics and subcategorized biopsy results for thyroid nodules of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) to stratify the risk of malignancy. Methods: Data included 672 thyroid nodules from 656 patients from a historical cohort. We analyzed ultrasound images of thyroid nodules and biopsy results according to nuclear atypia and architectural atypia. Multivariate logistic regression analysis was performed to predict whether nodules were diagnosed as malignant or benign. Results: The ultrasound features, including spiculated margin, marked hypoechogenicity, calcifications, biopsy results, and cytologic atypia, showed significant differences between groups. A 13‐point risk scoring system was developed, and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the development and validation sets were 0.837 and 0.830, respectively ( http://www.gap.kr/thyroidnodule_b3.php). Conclusion: We devised a web‐based predictive model using the combined information of ultrasound characteristics and biopsy results for AUS/FLUS thyroid nodules to stratify the malignant risk. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid cancer (PTC) is a common malignancy diagnosed during pregnancy. However, there is little information on the behavior of PTC during pregnancy. The aim of this study was to evaluate the natural course of PTC in pregnant women. Methods: The study included 19 patients with PTC who delayed thyroid surgery because they were diagnosed with PTC just before or during the early stages of pregnancy. Serial neck ultrasonography (US) was used to evaluate PTCs before surgical treatment and the clinical outcomes after surgery. Results: The median maximal PTC size at initial diagnosis on US was 0.91 cm (interquartile range [IQR] 0.61-1.11), and 13/19 (68.4%) patients had micro-PTCs (≤1 cm). The median maximal PTC size after a median 9.5 months of follow-up was 0.98 cm (IQR 0.72-1.12). There were three (16%) patients who showed a size increase, and five (26%) patients showed a volume increase during the follow-up periods. There was no clinically relevant change in the maximal tumor size during the follow-up period ( p = 0.16). Serial US measurements of PTC size in seven available patients in each trimester showed no significant differences between the different trimesters (first vs. second trimester p = 0.81; second vs. third trimester p = 0.99). No newly developed lesions in the thyroid or cervical lymph nodes were detected by neck US during the follow-up period. Among 19 patients, 16 underwent thyroid surgery after delivery, and the median duration from diagnosis to surgery was 11.9 months. Conclusions: No clinically relevant changes associated with a progression of PTC were observed during pregnancy. Delayed thyroid surgery with active surveillance can be an appropriate approach for pregnant patients with PTC. [ABSTRACT FROM AUTHOR]

Background: The reported malignancy rates of thyroid nodules that appear suspicious on ultrasound (US) but yield benign fine-needle aspiration (FNA) cytology results range from 13.6% to 56.6%. However, the malignancy risk of nodules that are discordant on US and core-needle biopsy (CNB) pathological findings has not been evaluated. This study evaluated the malignancy risk associated with thyroid nodules that are suspicious on US but yield benign CNB results. Methods: Between July 2008 and November 2011, 1309 patients with 1313 thyroid nodules underwent US-guided CNB. Among these, 166 thyroid nodules that were suspicious on US but yielded benign CNB results were retrospectively reviewed. Benign nodules were diagnosed by surgery, FNA, and/or CNB that was repeated at least twice or CNB and lesion size stability on follow-up. The malignancy risk of US-pathology discordant nodules was calculated according to recommendations by Moon et al., and a further evaluation was conducted using four different US risk systems. Factors that differentiated benign from malignant nodules were assessed using the chi-square test or Fisher's exact test. Moreover, the histological findings of US-pathology discordant nodules were analyzed. Results: Patients with benign and malignant nodules did not differ significantly regarding clinical and demographic characteristics. Of the 166 US-pathology discordant nodules, seven (4.2%) were confirmed malignant. The malignancy risks associated with the five US risk systems ranged from 3.6% to 5.5%. Regarding suspicious US features, only the number of suspicious features was associated with malignancy ( p = 0.002). Histological analysis of benign CNB specimens with suspicious US features revealed fibrosis (77.6%), thyroiditis (28.7%), calcifications (10.6%), and hemosiderin deposition (6.4%). Conclusions: The malignancy risk among thyroid nodules with discordant US and CNB results ranged from 3.6% to 5.5%, depending on US risk systems. However, repeated biopsy may be necessary for selected thyroid nodules with more than two suspicious US features. [ABSTRACT FROM AUTHOR]

Background: An initial clinical assessment is described of a new, commercially available, computer-aided diagnosis (CAD) system using artificial intelligence (AI) for thyroid ultrasound, and its performance is evaluated in the diagnosis of malignant thyroid nodules and categorization of nodule characteristics. Methods: Patients with thyroid nodules with decisive diagnosis, whether benign or malignant, were consecutively enrolled from November 2015 to February 2016. An experienced radiologist reviewed the ultrasound image characteristics of the thyroid nodules, while another radiologist assessed the same thyroid nodules using the CAD system, providing ultrasound characteristics and a diagnosis of whether nodules were benign or malignant. The diagnostic performance and agreement of US characteristics between the experienced radiologist and the CAD system were compared. Results: In total, 102 thyroid nodules from 89 patients were included; 59 (57.8%) were benign and 43 (42.2%) were malignant. The CAD system showed a similar sensitivity as the experienced radiologist (90.7% vs. 88.4%, p > 0.99), but a lower specificity and a lower area under the receiver operating characteristic (AUROC) curve (specificity: 74.6% vs. 94.9%, p = 0.002; AUROC: 0.83 vs. 0.92, p = 0.021). Classifications of the ultrasound characteristics (composition, orientation, echogenicity, and spongiform) between radiologist and CAD system were in substantial agreement (κ = 0.659, 0.740, 0.733, and 0.658, respectively), while the margin showed a fair agreement (κ = 0.239). Conclusion: The sensitivity of the CAD system using AI for malignant thyroid nodules was as good as that of the experienced radiologist, while specificity and accuracy were lower than those of the experienced radiologist. The CAD system showed an acceptable agreement with the experienced radiologist for characterization of thyroid nodules. [ABSTRACT FROM AUTHOR]

Objectives: To present the various complications of ultrasound (US)-guided core needle biopsy (CNB) of thyroid lesions in a large patient series.Methods: From January 2008 to March 2013, 6,169 patients underwent US-guided CNB of 6,687 thyroid nodules at a single institution. We assessed the number and types of major and minor complications, and evaluated the factors associated with complications.Results: Overall, 53 complications were observed in 50 patients (0.81 %), including 4 major and 49 minor complications. The major complications were massive haematoma (n = 2), pseudoaneurysm (n = 1) and voice change leading to disability that lasted for more than 30 days (n = 1). The minor complications were small to moderate haematoma (n = 42), carotid injury (n = 2), voice change that recovered within 30 days (n = 3), tracheal puncture (n = 1) and dysphagia (n = 1). Oedema (n = 12), vertebral puncture (n = 3) and vasovagal reaction (n = 1) were recorded as side effects. The presence of a coprocedure was the only significant factor associated with complications after thyroid CNB (P = 0.023).Conclusions: US-guided CNB of thyroid lesions was found in a large population to be a safe procedure with a low complication rate.Key Points: • The complication rate after US-guided CNB for thyroid lesions was 0.81 % (50/6,169). • The rate of major complications was 0.06 % (4/6,169). • Vascular injury was the most common complication (47/6,169; 0.76 %). • None of the patients experienced permanent problems resulting from complications. [ABSTRACT FROM AUTHOR]

Objective The follicular variant of papillary thyroid carcinoma (FVPTC) has multiple histological subtypes. Clinical outcomes of FVPTC are variable depending on the subtypes. This study evaluated the association of pre-operative ultrasonographic (US) findings and clinico-pathological features of FVPTC. Patients This retrospective study enrolled patients with FVPTC (n = 70), size-matched classical variant of papillary thyroid carcinoma (CPTC, n = 328), follicular carcinoma (n = 85) and follicular adenoma (FA, n = 120). We denned the histological subtypes of FVPTC as innltrative (I-FVPTC; n = 19) or encapsulated (E-FVPTC; n = 51) according to the presence of a fibrous capsule. Pre-operative US was reviewed using a US scoring system and classified into low US score (n = 42) and high US score (n = 28). Results The median US score for FVPTC was lower than CPTC (2 vs 7, P < 0-001), but higher than FA (2 vs 0, P < 0-001). The median US score for I-FVPTC was significantly higher than E-FVPTC (4 vs 2, P = 0-009). I-FVPTC was more likely to be diagnosed as a malignancy or suspicious for malignancy on cytology than E-FVPTC (P = 0-002). The cumulative risks of cervical lymph node (LN) or distant metastasis according to tumour size were significantly higher in I-FVPTC than E-FVPTC (all P < 0-001). The cumulative risks for cervical LN metastasis or capsular invasion according to tumour size were significantly higher in FVPTC with high US score than FVPTC with low US score (P = 0-005, P < 0-001, respectively). Conclusions Pre-operative US findings of thyroid nodules were associated with not only histological subtypes, but also the clinical behaviour in FVPTC. [ABSTRACT FROM AUTHOR]

Objective Serum calcitonin ( CT) level is used to detect medullary thyroid carcinoma ( MTC), but the cut-off level is unclear. We aimed at identifying the optimal cut-off value of basal serum CT levels for detecting MTC. Design and patients We retrospectively enrolled patients with hypercalcitoninemia (≥2·9 pmol/l) who had undergone thyroid ultrasonography ( US) and subsequent work-up between 2001 and 2013 at Asan Medical Center. We divided patients into four groups: proven MTC (group 1, n = 93), pathologically proven non- MTC after surgery (group 2, n = 57), benign single nodule by cytology (group 3, n = 68) and patients without nodules on US (group 4, n = 24). Measurement Basal serum CT levels were evaluated. Results The median CT level of group 1 (119·5 pmol/l) was significantly higher than those of other groups (4·0, 3·8 and 3·8 pmol/l, P < 0·001). When we adopted 19·0 pmol/l of CT level as a cut-off value, the sensitivity, specificity, and positive and negative predictive values were 77·4%, 98·7%, 97·3% and 87·8%, respectively. When we compared 29·2 pmol/l (100 pg/ml) and 19·0 pmol/l (65 pg/ml) as cut-off values, 19·0 pmol/l was more sensitive and accurate than 29·2 pmol/l. Factors associated with hypercalcitoninemia in non- MTC groups were autoimmune thyroiditis, chronic kidney disease, proton pump inhibitors and other malignancies. Serum CT levels tended to decrease spontaneously in non- MTC groups. Conclusion Basal serum CT levels higher than 19·0 pmol/l can be a useful cut-off value for detecting macroscopic MTC, even though values below 19·0 pmol/l cannot exclude the presence of MTC like small volume MTC or premalignant C-cell hyperplasia. [ABSTRACT FROM AUTHOR]

Background: Low serum vitamin D levels have been associated with several autoimmune diseases, but their association with thyroid autoimmunity is unclear. We evaluated the association of serum vitamin D levels with the prevalence of autoimmune thyroid disease (AITD). Methods: Our cross-sectional study included subjects who underwent routine health checkups, which included assays of serum 25-hydroxy vitamin D3 [25(OH)D3] and anti-thyroid peroxidase antibody (TPO-Ab), as well as thyroid ultrasonography (US) between 2008 and 2012 at the Asan Medical Center. We defined AITD according to the levels of TPO-Ab and US findings. Results: A total of 6685 subjects (58% male; 42% female) were enrolled for this study. Overall prevalence of TPO-Ab positivity and both TPO-Ab/US positivity were 10.1% (6.3% male; 15.3% female) and 5.4% (2.3% male; 9.7% female) respectively. In female subject s, mean serum 25(OH)D3 levels were significantly lower in the TPO-Ab(+) (22.0 vs. 23.5 ng/mL, p=0.030) and TPO-Ab(+)/US(+) groups (21.6 vs. 23.4 ng/mL, p=0.027) compared with the control group, respectively. According to the levels of serum 25(OH)D3, the prevalence of TPO-Ab positivity (21.2%, 15.5%, and 12.6% in deficient, insufficient, and sufficient group, respectively; p=0.001) and both TPO-Ab and US positivity (14.7%, 9.9%, and 7.1% in deficient, insufficient, and sufficient group, respectively; p<0.001) decreased in female subjects. Interestingly, this pattern was significant only in pre-menopausal women ( p=0.003 and p<0.001; respectively), but not in postmenopausal women. Multivariate analysis indicated that the adjusted odds ratios (OR) for AITD among those in the 25(OH)D3-deficient [TPO-Ab(+): OR 1.95, p=0.001; TPO-Ab(+)/US(+): OR 2.36, p<0.001] and -insufficient groups [TPO-Ab(+): OR 1.31, p=0.043; TPO-Ab(+)/US(+): OR 1.50, p=0.017] were significantly increased when compared with the sufficient group. Conclusions: The levels of serum vitamin D were significantly lower in pre-menopausal women with AITD. Vitamin D deficiency and insufficiency were significantly associated with AITD in pre-menopausal women. [ABSTRACT FROM AUTHOR]

We prospectively screened consecutive patients with Graves’ hyperthyroidism by ultrasonography (USG), regardless of presence of palpable nodules, and evaluated patients with nodule(s) by fine-needle aspiration (FNA) and by resulting surgery to define the prevalence of thyroid cancer in patients with Graves’ disease. Two hundred and forty-five consecutive Graves’ disease patients without prior thyroid surgery or radio-iodine treatment were enrolled at Asan Medical Centre endocrinology clinic. All patients with nodule(s) of 5 mm or greater were reviewed for evaluation by FNA, and of these 90·0% ( n = 62) underwent FNA. All patients with suspicious/malignant cytology or those with positive immunostaining with GAL-3 antibody underwent surgery. Among 245 patients, thyroid nodule(s) were detected in 35·1% (86/245) by USG. Nodule prevalence significantly increased according to age, which was the only significant variable predicting the presence of nodule(s) in logistic regression analysis. Among patients with thyroid nodule(s), 69 patients had nodule(s) of 5 mm or greater in size, and 62 cases of them (90·0%) underwent FNA. In eight patients, thyroid cancers were histologically confirmed (all papillary thyroid cancers), so the prevalence of thyroid cancer was at least 3·3% (8/245) in Graves’ patients. Of eight patients with thyroid cancer, only one case was detected by palpation and the other seven patients were detected only by USG. In pathologic examination, mean size of tumour was 10·0 ± 6·7 mm (5–25 mm), three cases had extrathyroidal extension (37·5%), four cases had cervical node metastasis (50·0%) and one case had multifocal tumour (12·5%). Thus, five of eight patients had locally advanced cancers (pT4 or pN1 lesion), but none had distant metastasis. Prevalence of thyroid cancers in Graves’ disease tended to be higher in patients of 45 years or greater than younger patients (6·7% vs. 1·3%, P = 0·05), and that of the locally advanced cancers was significantly higher in older patients (5·6% vs. 0%, P < 0·05). Older age of the patient was the only significant factor predicting the presence of locally advanced thyroid cancers regardless of duration/severity of hyperthyroidism, goitre size, or of TBII activity. The prevalence of thyroid cancer in Graves’ patients was at least 3·3% in this prospective analysis; most of them were micropapillary thyroid cancers. Stimulating TSHR antibodies seems not to induce nodule/cancer formation and not to change biologic behaviour of thyroid cancers in Graves’ patients. Graves’ patients of 45 years of age or above are more likely to harbour locally advanced thyroid cancers than younger patients, regardless of duration or severity of hyperthyroidism, goitre size, or of TBII activity. [ABSTRACT FROM AUTHOR]

Abstract: The aims were to determine the reliability of ultrasound elastography (USE) and the factors related to reliability. One hundred six solid thyroid nodules in 78 consecutive patients were enrolled. Conventional ultrasound examination and USE were performed for each nodule. We evaluated reliability, the factors affecting reliability of USE and the interobserver and intraobserver agreement. We suggest following three criteria as less reliable results: (1) <50% green color in the region of interest box for the thyroid parenchyma; (2) discordance in elasticity scores in the three USE images; and (3) intranodular color signal loss. Consensual reliability of USE was 68% (72/106). Multivariable logistic regression analysis revealed that rim calcification (p = 0.002), a compressive force of ≥3 (p < 0.001) and arterial pulsation (p < 0.001) were significantly associated with reliability of USE. Substantial interobserver (κ = 0.738) and intraobserver agreement were observed in reliable USE results (κ = 0.765). Clinical application of USE should be restricted to the thyroid nodules with reliable results. [Copyright &y& Elsevier]