Project description:ObjectivePatient-centered decision making is increasingly identified as a desirable component of medical care. To manage indeterminate thyroid nodules, patients are offered the options of surveillance, diagnostic hemithyroidectomy, or molecular testing. Our objective was to identify factors associated with decision making in this population.Study designThis is a retrospective cross-sectional study of patients with Bethesda III and IV thyroid nodules.SettingMulti-institutional.MethodsFactors of interest included age, sex, socioeconomic status (SES), nodule size, institution, attending surgeon, surgeon payment model, and hospital type. Our outcome of interest was the initial management decision made by patients.ResultsA total of 956 patients were included. The majority of patients had Bethesda III nodules (n = 738, 77%). A total of 538 (56%) patients chose surgery, 413 (43%) chose surveillance, and 5 (1%) chose molecular testing. There was a significant variation in management decision based on attending surgeon (proportion of patients choosing surgery: 15%-83%; P≤.0001). Fee-for-service surgeon payment models (odds ratio [OR], 1.657; 95% CI, 1.263-2.175; P < .001) and community hospital settings (OR, 1.529; 95% CI, 1.145-2.042; P < .001) were associated with the decision for surgery. Larger nodule size, younger patients, and Bethesda IV nodules were also associated with surgery.ConclusionWhile it seems appropriate that larger nodules, younger age, and higher Bethesda class were associated with decision for surgery, we also identified attending surgeon, surgeon payment model, and hospital type as important factors. Given this, standardizing management discussions may improve patient-centered shared decision making.
Project description:Thyroid nodules are a common disease, and fine needle aspiration cytology (FNAC) is the primary method to assess their malignancy. For the diagnosis of follicular thyroid nodules, however, FNAC has limitations. FNAC can classify them only as Bethesda IV nodules, leaving their exact malignant status and pathological type undetermined. This imprecise diagnosis creates difficulties in selecting the follow-up treatment. In this retrospective study, we collected ultrasound (US) image data of Bethesda IV thyroid nodules from 2006 to 2022 from five hospitals. Then, US image-based artificial intelligence (AI) models were trained to identify the specific category of Bethesda IV thyroid nodules. We tested the models using two independent datasets, and the best AI model achieved an area under the curve (AUC) between 0.90 and 0.95, demonstrating its potential value for clinical application. Our research findings indicate that AI could change the diagnosis and management process of Bethesda IV thyroid nodules.
Project description:PurposeMalignancy prediction in indeterminate thyroid nodules is still challenging. We prospectively evaluated whether the combination of ultrasound (US) risk stratification and molecular testing improves the assessment of malignancy risk in Bethesda Category IV thyroid nodules.MethodsNinety-one consecutively diagnosed Bethesda Category IV thyroid nodules were prospectively evaluated before surgery by both ACR- and EU-TIRADS US risk-stratification systems and by a further US-guided fine-needle aspiration cytology (FNAC) for the following molecular testing: BRAFV600E, N-RAS codons 12/13, N-RAS codon 61, H-RAS codons 12/13, H-RAS codon 61, K-RAS codons 12/13, and K-RAS codon 61 point-mutations, as well as PAX8/PPARγ, RET/PC1, and RET/PTC 3 rearrangements.ResultsAt histology, 37% of nodules were malignant. No significant association was found between malignancy and either EU- or ACR-TIRADS. In total, 58 somatic mutations were identified, including 3 BRAFV600E (5%), 5 N-RAS 12/13 (9%), 13 N-RAS 61 (22%), 7 H-RAS 12/13 (12%), 11 H-RAS 61 (19%), 6 K-RAS 12/13 (10%), 8 K-RAS 61 (14%) mutations and 2 RET/PTC1 (4%), 0 RET/PTC 3 (0%), 3 PAX8/PPARγ (5%) rearrangements. At least one somatic mutation was found in 28% and 44% of benign and malignant nodules, respectively, although malignancy was not statistically associated with the outcome of the mutational test. However, the combination of ACR-, but not EU-, TIRADS with the presence of at least one somatic mutation, was significantly associated with malignant histology (P = 0.03).ConclusionUS risk stratification and FNAC molecular testing may synergistically contribute to improve malignancy risk estimate of Bethesda category IV thyroid nodules.
Project description:Background Ultrasound guided fine-needle aspiration (FNA) is a standard procedure for thyroid nodules management and selecting patients for surgical treatment. Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS), as stated by The Bethesda System for Reporting Thyroid Cytopathology, is a diagnostic category with an implied malignancy risk of 5-15%. The aim of our study was to review cytology and histopathology reports, as well as clinical and ultrasound data, for thyroid nodules reported as AUS/FLUS, in order to evaluate the malignancy rate and to assess factors associated with malignant outcome. Patients and methods A total of 112 AUS/FLUS thyroid nodules in 105 patients were evaluated, of which 85 (75.9%) were referred to surgery, 21 (18.8%) were followed-up by repeat FNA and 6 nodules (5.3%) were clinically observed. Each was categorized in two final diagnostic groups - benign or malignant, which were further compared to clinical data of patients and ultrasonographic features of the nodules. Results Final diagnosis of malignancy was reached in 35 cases (31.2%) and 77 (68.8%) had benign lesions. The most frequent type of cancer was papillary thyroid carcinoma (PTC) - 58.1% PTC and 25.8% had follicular variant of PTC. Patients' younger age, smaller nodule size, hypoechoic nodule and presence of calcifications were shown to be statistically significant risk factors for malignancy. Conclusions The rate of malignancy for the AUS/FLUS diagnostic category in our study was higher than estimated by the Bethesda System. Clinical and ultrasound factors should be considered when decision for patient treatment is being made.
Project description:BackgroundFine-needle aspiration (FNA) is the most dependable tool to triage thyroid nodules for medical or surgical management. However, Bethesda class III cytology, namely "follicular lesion of undetermined significance" (FLUS) or "atypia of undetermined significance" (AUS), is a major limitation of the US-FNA in assessing thyroid nodules. As the most important imaging method, ultrasound (US) has a high efficacy in diagnosing thyroid nodules. This meta-analysis aimed to assess the role of US in evaluating Bethesda class III thyroid nodules.MethodsWith keywords "Undetermined Significance," "Bethesda Category III," "Bethesda system," "Cytological Subcategory," "AUS/FLUS," "Atypia of Undetermined Significance," and "Ultrasound/US," papers in PubMed, Cochrane Library, Medline, Web of Science, Embase, and Google Scholar from inception to December 2016 were searched. A meta-analysis of these trials was then performed for evaluating the diagnostic value of thyroid ultrasound in Bethesda Category III thyroid nodules.ResultsFourteen studies including 2405 nodules were analyzed. According to the criteria for US diagnosis of thyroid nodules in each article, with any one of suspicious features as indictors of malignancy, US had a pooled sensitivity of 0.75 (95% CI 0.72-0.78) and a pooled specificity of 0.48 (95% CI 0.45-0.50) in evaluating Bethesda Class III Nodules. The pooled diagnostic odds ratio was 10.92 (95% CI 6.04-19.74). The overall area under the curve was 0.84 and the Q* index was 0.77. With any 2 or 3 of US suspicious features as indictors of malignancy, the sensitivity and specificity were 0.77 (95% CI 0.71-0.83) and 0.54 (95% CI 0.51-0.58), 0.66 (95% CI 0.59-0.73) and 0.71 (95% CI 0.68-0.74), respectively.ConclusionsUS was helpful for differentiating benign and malignant Bethesda class III thyroid nodules, with the more suspicious features, the more likely to be malignant.
Project description:BACKGROUND:Studies indicate that mild to moderate iodine deficiency in pregnancy may have a long-term negative impact on child neurodevelopment. These effects are likely mediated via changes in maternal thyroid function, since iodine is essential for the production of thyroid hormones. However, the impact of iodine availability on thyroid function during pregnancy and on thyroid function reference ranges are understudied. The aim of this study was to investigate the association between iodine intake and thyroid function during pregnancy. DESIGN:In a population-based pregnancy cohort including 2910 pregnant women participating in The Norwegian Mother and Child Cohort Study, we explored cross sectional associations of maternal iodine intake measured (1) by a food frequency questionnaire and (2) as iodine concentration in a spot urine sample, with plasma thyroid hormones and antibodies. RESULTS:Biological samples were collected in mean gestational week 18.5 (standard deviation 1.3) and diet was assessed in gestational week 22. Median iodine intake from food was 121??g/day (interquartile range 90, 160), and 40% reported use of iodine-containing supplements in pregnancy. Median urinary iodine concentration (UIC) was 59??g/L among those who did not use supplements and 98??g/L in the women reporting current use at the time of sampling, indicating mild to moderate iodine deficiency in both groups. Iodine intake as measured by the food frequency questionnaire was not associated with the outcome measures, while UIC was inversely associated with FT3 (p?=?0.002) and FT4 (p?<?0.001). Introduction of an iodine-containing supplement after gestational week 12 was associated with indications of lower thyroid hormone production (lower FT4, p?=?0.027, and nonsignificantly lower FT3, p?=?0.17). The 2.5th and 97.5th percentiles of TSH, FT4, and FT3 were not significantly different by groups defined by calculated iodine intake or by UIC. CONCLUSION:The results indicate that mild to moderate iodine deficiency affect thyroid function in pregnancy. However, the differences were small, suggesting that normal reference ranges can be determined based on data also from mildly iodine deficient populations, but this needs to be further studied. Introducing an iodine-containing supplement might temporarily inhibit thyroid hormone production and/or release.
Project description:BackgroundWhereas the adverse effects of severe iodine deficiency during pregnancy are well documented, the effects of mild-to-moderate deficiency are not well established.ObjectivesWe aimed to explore whether iodine nutrition and timing of iodine supplement initiation are associated with thyroid function in pregnant and postpartum women.MethodsIn this cohort study, 137 pregnant women were enrolled and followed up at gestational weeks (GWs) 18 and 36, and 3 and 6 mo postpartum. Thyroid function tests [thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4)], urinary iodine and creatinine concentration (UIC:Cr), and iodine intake (including iodine supplement use) were measured at each time point. The associations between thyroid hormone concentrations and UIC:Cr, iodine intakes, and iodine supplement use were estimated using multiple generalized estimating equation models.ResultsThe median UIC at GW18 was 94 μg/L, indicating mild-to-moderate iodine deficiency. UIC:Cr (β; 95% CI) per 100 μg/g was negatively associated with fT3 (-0.191; -0.331, -0.051) and fT4 (-0.756; -1.372, -0.141) concentrations. Iodine intake (β; 95% CI) per 100 μg/d was positively associated with TSH (0.099; 0.022, 0.177), and negatively associated with fT3 (-0.084; -0.0141, -0.027) and fT4 (-0.390; -0.599, -0.182) concentrations. Compared with no use of supplement, those initiating an iodine-containing supplement prepregnancy and continuing through pregnancy had lower TSH (estimated means) (1.35 compared with 1.68 mIU/L, P = 0.021), and higher fT3 (4.48 compared with 4.28 pmol/L, P = 0.035) and fT4 (15.2 compared with 14.4 pmol/L, P = 0.024) concentrations.ConclusionsLower iodine availability during pregnancy and postpartum was associated with lower TSH, and higher fT3 and fT4 concentrations. The use of an iodine-containing supplement that was initiated prepregnancy and continuing through pregnancy was associated with lower TSH, and higher fT3 and fT4 concentrations, which may suggest improved thyroid function. These findings support the notion that optimization of iodine intake should start before pregnancy.This trial was registered at clinicaltrials.gov as NCT02610959.
Project description:The aim of the study was to analyze the diagnostic usefulness of the combined assessment of the ultrasound risk category of the nodule (evaluated with EU-TIRADS system), the presence of BRAF V600E mutation and the expression of selected microRNAs (miR-146b, miR-221 and miR-222) in Bethesda category III thyroid nodules, separately for cases with nuclear atypia (AUS-nuclear) and cases with other types of atypia (AUS-other). We evaluated 161 nodules (66 AUS-nuclear and 95 AUS-other) with known results of postoperative histopathological examination. The rate of cancer and the rate of PTC among cancers were nearly three times higher in the AUS-nuclear than the AUS-other group. For AUS-nuclear nodules, the most effective diagnostic panel included, in addition to repeat FNA, the assessment of BRAF V600E mutation and the expression of miR-146b and miR-222 (sensitivity: 93.5%, specificity: 80.0%). For AUS-other nodules, a two-step procedure was most effective: at the first stage, forgoing surgical treatment in subjects with a benign repeat FNA outcome, and, at the second stage, the assessment of miR-222 expression and the EU-TIRADS category (sensitivity: 92.3%, specificity: 76.8%). The optimal use of molecular methods in the diagnostics of category III thyroid nodules requires a separate approach for nodules with nuclear atypia and nodules with other types of atypia.