The Diagnostic Efficacy of the American College of Radiology (ACR) Thyroid Imaging Report and Data System (TI-RADS) and the American Thyroid Association (ATA) Risk Stratification Systems for Thyroid Nodules

Background. This study is aimed at evaluating the diagnostic efficacy of ultrasound-based risk stratification for thyroid nodules in the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and the American Thyroid Association (ATA) risk stratification systems. Methods. 286 patients with thyroid cancer were included in the tumor group, with 259 nontumor cases included in the nontumor group. The ACR TI-RADS and ATA risk stratification systems assessed all thyroid nodules for malignant risks. The diagnostic effect of ACR and ATA risk stratification system for thyroid nodules was evaluated by receiver operating characteristic (ROC) analysis using postoperative pathological diagnosis as the gold standard. Results. The distributions and mean scores of ACR and ATA rating risk stratification were significantly different between the tumor and nontumor groups. The lesion diameter > 1 cm subgroup had higher malignant ultrasound feature rates detected and ACR and ATA scores. A significant difference was not found in the ACR and ATA scores between patients with or without Hashimoto’s disease. The area under the receiver operating curve (AUC) for the ACR TI-RADS and the ATA systems was 0.891 and 0.896, respectively. The ACR had better specificity (0.90) while the ATA system had higher sensitivity (0.92), with both scenarios having almost the same overall diagnostic accuracy (0.84). Conclusion. Both the ACR TI-RADS and the ATA risk stratification systems provide a clinically feasible thyroid malignant risk classification, with high thyroid nodule malignant risk diagnostic efficacy.

Treatment of thyroid dysfunction in a medical specialist’s office – the role of levothyroxine

Synthetic levothyroxine is the first line treatment for hypothyroidism, one of the most common endocrine disorders, independently its cause, in all age groups. The Polish Endocrinological Society, together with European Thyroid Association, American Thyroid Association and American Association of Clinical Endocrinologists, do not recommend the use of dried thyroid preparations, triiodothyronine or combined preparations of thyroxine with triiodothyronine. The objective of treatment is to achieve biochemical and clinical euthyroidism monitored by TSH and/or FT4 levels. The daily dose of levothyroxine depends on many factors, including the etiology and severity of hypothyroidism, age, body weight, pregnancy and comorbidities. Routinely, levothyroxine is administered on an empty stomach at least 30 minutes before breakfast (ATA 2014 recommend up to 60 minutes interval between meal and taking the drug). Levothyroxine can also be used in combination therapy in Graves’ disease. Currently, the routine use of synthetic sodium levothyroxine in patients with multinodular goiter is not recommended because it increases the risk of osteoporosis in postmenopausal women and atrial fibrillation in patients after 60 year of life.

Antithyroglobulin Antibody Variation During Follow-Up Has a Good Prognostic Value for Preoperative Antithyroglobulin Antibody-Positive Differentiated Thyroid Cancer Patients: A Retrospective Study in Southwest China

ObjectiveAntithyroglobulin antibody (TgAb) is a potential tumour marker for detecting differentiated thyroid cancer (DTC) recurrence, but insufficient data have supported its clinical applications. Our study aimed to describe the changing trend of TgAb after surgery and identify the relationship between this trend and clinical outcomes.Patients and MethodsWe reviewed the electronic records of 1,686 DTC patients who had undergone total thyroidectomy (TT) and radioactive iodine (131I) therapy at West China Hospital of Sichuan University from January 2015 to December 2017. Finally, 289 preoperative TgAb-positive DTC patients were included and divided into four subgroups depending on the clinical outcome: Group A (tumour free), Group B (uncertain), Group C (incomplete biochemical response), and Group D (structural disease). The patient demographics, tumour characteristics, operations, pathology reports, and all serological biomarkers were reviewed and compared, and the prognostic efficacy of TgAb was evaluated.ResultsAmong all 1,686 patients, 393 (23.65%) were TgAb positive (>40 IU/ml) preoperatively. The TgAb level in Group A decreased significantly after surgery and 131I therapy and stabilised at a low level after 1–2 years of 131I therapy. However, in the other three groups, the decrease in TgAb was not significant after treatment. Conversely, TgAb declined slowly and remained stable or increased. The variations in TgAb relative to the preoperative level of Group A were significantly larger than those of Groups B, C, and D at most time points of follow-up (p < 0.001). By receiver operating characteristic (ROC) analyses, the variations of TgAb > −77.9% at 6 months after 131I therapy (area under the curve (AUC) = 0.862; p < 0.001) and TgAb > −88.6% at 2 years after 131I therapy (AUC = 0.901; p < 0.001) had good prognostic efficacy in tumour-free survival. When the variation in TgAb > −88.6% at 2 years after 131I therapy was incorporated as a variable in the American Thyroid Association (ATA) categories, both intermediate- and high-risk patients also had a significantly increased chance of being tumour free (from 75.68% to 93.88% and 42.0% to 82.61%, respectively).ConclusionsFor preoperative TgAb-positive DTC patients, variations in TgAb > −77.9% at 6 months after 131I therapy and TgAb > −88.6% at 2 years after 131I therapy had good prognostic efficacy. Their incorporation as variables in the ATA risk stratification system could more accurately predict disease-free survival.

Comparative Study of ACR TI-RADS and ATA 2015 for Ultrasound Risk Stratification of Thyroid Nodules

Objective To study the adoption rate of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) scoring system over a 3-year period in a community setting and compare its performance with that of the American Thyroid Association 2015 (ATA 2015) ultrasound risk scoring system. Study Design Case series with prospective data collection and retrospective chart review. Setting Large community-based practice with multiple satellite offices and a dedicated thyroid ultrasound clinic. Methods All patients referred to the thyroid clinic between January 2018 and December 2020 for ultrasound-guided fine-needle biopsy were assigned an ATA 2015 risk score in a prospective manner immediately prior to biopsy. ACR TI-RADS scores were recorded through retrospective chart review of the radiologist report. Performance of the 2 systems was compared with cytology as the gold standard. Results A total of 949 nodules underwent biopsy, of which 236 had available data for both scoring systems. There was a 33.8% increase in adoption of the ACR TI-RADS over the 3-year study period. The ATA 2015 guidelines yielded sensitivity and specificity of 81.6% and 54.5%, respectively, as opposed to 73.7% and 27.0% for the ACR TI-RADS. Conclusion In our community, there has been a gradual increase in adoption of the ACR TI-RADS, although the ATA 2015 risk scoring system has performed better.

Pregnancy and Neonatal Outcomes With Levothyroxine Treatment in Women With Subclinical Hypothyroidism Based on New Diagnostic Criteria: A Systematic Review and Meta-Analysis

BackgroundSubclinical hypothyroidism (SCH) during pregnancy has been associated with multiple adverse maternal and neonatal outcomes. However, the potential benefits of levothyroxine (LT4) supplementation remain controversial. Variations across studies in diagnostic criteria for SCH may, in part, explain the divergent findings on the subject. This study aimed to assess the effect of LT4 treatment on pregnancy and neonatal outcomes among pregnant women who were diagnosed as SCH based on the most recent diagnostic criteria.MethodsWe conducted a systematic review and meta-analysis of the literature published from inception to January 2020. The search strategy targeted the studies on pregnancy and neonatal outcomes following LT4 treatment in women with SCH based on 2017 American Thyroid Association diagnostic criteria. Pooled effect sizes were estimated using fixed and random effect models, according to the absence or presence of heterogeneity which was assessed using the I-squared statistic. Sources of heterogeneity and the stability of results were evaluated through sensitivity analysis.ResultsOf the 2781 identified references, 306 full-text articles were screened for eligibility. Finally, 6 studies including a total of 7955 participants were retained for analysis. Summary effect estimates indicated that pregnant women with SCH treated with LT4 had a lower risk of pregnancy loss [odds ratio (OR) = 0.55, 95% confidence interval (CI): 0.43-0.71], preterm birth (OR=0.63, 95% CI: 0.41-0.98) and gestational hypertension (OR = 0.78, 95% CI: 0.63-0.97) than those in control group.ConclusionLT4 treatment in pregnant women with SCH may reduce the risk of pregnancy loss, preterm delivery and gestational hypertension.

Mild Anemia May Affect Thyroid Function in Pregnant Chinese Women During the First Trimester

BackgroundPregnant women are often susceptible to anemia, which can damage the thyroid gland. However, compared with moderate and severe anemia, less attention has been paid to mild anemia. The purpose of this study was to evaluate the effect of mild anemia on the thyroid function in pregnant women during the first trimester.MethodsA total of 1,761 women in the first trimester of their pregnancy were enrolled from Shenyang, China, and divided into mild anemia and normal control groups based on their hemoglobin levels. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels were compared between the two groups.ResultsThe TSH levels of pregnant women with mild anemia were higher than those of pregnant women without mild anemia (p < 0.05). Normal control women were selected to set new reference intervals for TSH, FT3, and FT4 levels during the first trimester, which were 0.11–4.13 mIU/l, 3.45–5.47 pmol/l, and 7.96–16.54 pmol/l, respectively. The upper limit of TSH 4.13 mU/l is close to the upper limit 4.0 mU/l recommended in the 2017 American Thyroid Association (ATA) guidelines, indicating that exclusion of mild anemia may reduce the difference in reference values from different regions. Mild anemia was related to 4.40 times odds of abnormally TSH levels (95% CI: 2.84, 6.76) and 5.87 increased odds of abnormal FT3 (95% CI: 3.89, 8.85). The proportion of hypothyroidism and subclinical hypothyroidism in patients with mild anemia was higher than that in those without anemia (0.6% vs. 0, p = 0.009; 12.1% vs. 1.9%, p < 0.001). Mild anemia was related to 7.61 times increased odds of subclinical hypothyroidism (95% CI: 4.53, 12.90).ConclusionsMild anemia may affect thyroid function during the first trimester, which highlights the importance of excluding mild anemia confounding when establishing a locally derived specific reference interval for early pregnancy.

ACR TI-RADS and ATA ultrasound classifications are helpful for the management of thyroid nodules located in the isthmus

PURPOSE: To compare the application value of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and the American Thyroid Association (ATA) guidelines in the risk stratification of thyroid isthmic nodules. METHODS: A total of 315 patients with thyroid isthmic nodules (315 nodules) confirmed by surgical pathology or fine-needle aspiration biopsy (FNAB) were selected in this retrospective study. The nodules were evaluated and classified according to ACR TI-RADS and the ATA guidelines. Taking pathological results as the reference, receiver operating characteristic (ROC) curves were drawn to evaluate the diagnostic capabilities of the ACR TI-RADS and the ATA guidelines for the risk stratification of thyroid isthmic nodules. The unnecessary biopsy rates and false-negative rates were compared. RESULTS: Multivariate analysis of ultrasonographic features of suspicious malignancies showed that an aspect ratio > 1 was not an independent risk factor for malignant thyroid nodules located in the isthmus (odds ratio: 3.193, 95%confidence interval: 0.882–11.552) (P = 0.077). The area under the ROC curves for diagnosing malignant thyroid nodules located in the isthmus in by the ACR TI-RADS and the ATA guidelines were 0.853 and 0.835, respectively. Under the management recommendations of the ACR TI-RADS and ATA guidelines, the false-negative rates of malignant thyroid nodules were 66.2%(ATA intermediate suspicion), 62.3%(ACR TR 4), 81.8%(ATA high suspicion) and 86.5%(ACR TR 5). CONCLUSION: Both the ACR TI-RADS and the ATA guidelines have high diagnostic capabilities for the risk stratification of thyroid isthmic nodules. For ACR TR 4 and 5 and ATA intermediate- and high-suspicion thyroid isthmic nodules with a maximum diameter < 1 cm, the criteria for puncture should be lowered, and FNAB should be done to clarify their diagnosis.

Systematic population-based identification of NTRK and RET fusion-positive thyroid cancers

Objective: The aim of the study was to identify patients with NTRK fusion-positive or RET fusion/mutation-positive thyroid cancers, who could benefit from TRK or RET inhibitors. Methods: Patients were identified in the Calgary prospective thyroid cancer database (N=482). Patients were “pre-screened” with clinically available MassARRAY® BRAF Test, Colon Panel, Melanoma Panel, or ThyroSPEC™. Mutation-negative tumors were “screened” for NTRK fusions and RET fusions/mutations with the Oncomine™ Comprehensive Assay v3 (OCAv3). Results: A total of 86 patients were included in one of two separate analyses. Analysis A included 42 patients with radioactive iodine (RAI)-resistant distant metastases. After pre-screening, 20 BRAF and RAS mutation-negative patients underwent OCAv3 screening, resulting in the detection of four patients with NTRK fusions and four patients with RET fusions (8/20, 40% of analyzed patients). Analysis B included 44 patients, 42 with American Thyroid Association (ATA) high and intermediate risk of recurrence and two with medullary thyroid carcinoma. During pre-screening one patient with an NTRK fusion, one patient with a RET fusion and 30 patients with BRAF mutations were identified. The remaining nine patients received OCAv3 screening, resulting in detection of one patient with an NTRK fusion and one with a RET fusion (4/11, 36% of analyzed patients). Conclusions: Our findings indicate a high rate of NTRK fusions and RET fusions in patients with thyroid cancer with RAI-resistant distant metastases, ATA high/intermediate risk of recurrence. This highlights the importance of early screening, to enable intervention with a TRK or RET inhibitor.

Modified Models for Predicting Malignancy Using Ultrasound Characters Have High Accuracy in Thyroid Nodules With Small Size

To assess the malignancy risk of thyroid nodules, ten ultrasound characteristics are suggested as key diagnostic markers. The European Thyroid Association Guidelines (EU-TIRADS) and 2015 American Thyroid Association Management Guidelines (2015ATA) are mainly used for ultrasound malignancy risk stratification, but both are less accurate and do not appropriatetly classify high risk patients in clinical examination. Previous studies focus on papillary thyroid carcinoma (PTC), but follicular thyroid carcinoma (FTC) and medullary thyroid carcinoma (MTC) remained to be characterized. Thus, this study aimed to determine the diagnostic accuracy and establish models using all ultrasound features including the nodule size for predicting the malignancy of thyroid nodules (PTC, FTC, and MTC) in China. We applied logistic regression to the data of 1,500 patients who received medical treatment in Shanghai and Fujian. Ultrasound features including taller-than-wide shape and invasion of the thyroid capsule showed high odds ratio (OR 19.329 and 4.672) for PTC in this dataset. Invasion of the thyroid also showed the highest odds ratio (OR = 8.10) for MTC. For FTC, the halo sign has the highest odds ratio (OR = 13.40). Four ultrasound features revealed distinct OR in PTC nodule groups with different sizes. In this study, we constructed a logistic model with accuracy up to 80%. In addition, this model revealed more accuracy than TIRADS in 4b and 4c category nodules. Hence, this model could well predict malignancy in small nodules and classify high-risk patients.

Thyroglobulin Levels in Patients who have Undergone Hemithyroidectomy for Differentiated Thyroid Cancer. An Assessment of Levels and Trends at a Tertiary Referral Centre

Serum thyroglobulin (Tg) and thyroglobulin antibody (TgAb) levels are used to monitor patients with differentiated thyroid cancer (DTC) after total thyroidectomy with or without radioiodine (RAI) ablation. However, they are also measured in patients who are treated with thyroid lobectomy (TL)/hemithyroidectomy (HT). Data on the levels of Tg and its trend in those undergoing TL/HT is sparse in India. We reviewed retrospective data of DTC patients who underwent TL/HT and were followed-up with postoperative Tg levels between 2015 and 2020. Out of 247 patients, 17 had undergone either TL or HT, which included papillary thyroid cancer (n = 12), follicular thyroid cancer (n = 4), and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 1 patient. All patients with DTC had tumor size < 4 cm (T1/2, clinical N0, Mx). The median follow-up was 15 months (range, 1–125) and the median Tg level was 7.5 ng/mL (interquartile range [IQR]; 3.6, 7.5) and ranged from 0.9 to 36.7 ng/mL. The median thyroid-stimulating hormone (TSH) level was 2.03 IU/L (IQR; 1.21, 3.59) and it ranged from 0.05 to 8.54 IU/L. As of last follow-up, none of them underwent completion thyroidectomy; however, eight patients had a decline in Tg ranging from 8 to 64%, four patients had increase in Tg ranging from 14 to 145%, three patients had stable Tg, and one of them had an increase in TgAb titers. As per American Thyroid Association (ATA) response-to-treatment category, six patients had indeterminate response, five patients had biochemical incomplete response, four patients had excellent response, and two did not have follow-up Tg and TgAb levels. While absolute values of Tg were well below 30 ng/mL in almost all patients with HT/TL, the Tg trends were difficult to predict, and only 23% of patients were able to satisfy the criteria for “excellent response” on follow-up. We suggest keeping this factor in mind in follow-up and while counselling for HT in patients with low-risk DTC.