The study aimed to investigate the BRAF V600E mutation and clinicopathological changes among patients with Hashimoto thyroiditis (HT), papillary thyroid carcinoma (PTC) with Hashimoto thyroiditis (HT), or nodular goiter (NG). A total of 87 patients with the BRAF V600E mutation who were diagnosed with HT (including with hyperplasia dysplasia), PTC with HT, and PTC with NG were enrolled. Clinical data, concentrations of antithyroglobulin antibodies (TGAb) and thyroid microsomal antibodies (TMAb) in the serum thyroid-function levels, and the result presence of the BRAF V600E mutation were retrospectively analyzed. There were significant differences in the BRAF V600E mutation rates between the HT and PTC with HT groups ( P <0.05) and the HT and PTC with NG groups ( P <0.05), whereas no significant difference was found between the PTC with HT and PTC with NG groups. There was no difference in incidences of PTC between HT with elevated TGAb and TMAb group and those with baseline levels. The incidence of multifocal PTC was higher in the PTC with HT group; however, the difference was not significant. Our findings documented that BRAF mutation distinguished between the benign HT and the malignant PTC groups. The serum levels of TGAb and TMAb autoantibodies did not directly correlate with PTC in the background of HT. HT and NG may similarly contribute to the pathogenesis of PTC.

Extrathyroid implantation or dissemination of thyroid tissue secondary to a thyroid procedure is rare. Most of these belonged to thyroid carcinoma with metastatic potential and uncommon for benign pathologies.
We report the case of a 31-year-old female who was identified to have multiple subcutaneous implantation of thyroid tissue 5 years after transoral endoscopic thyroidectomy vestibular approach. A comprehensive literature search on implantation of thyroid tissue secondary to thyroid procedures was performed.
Accidental tearing of the capsule during previous surgery may lead to the subcutaneous implantation. Through literature review, a total 29 articles with 47 patients were identified. 33.3% were benign lesions, and implantation was mostly secondary to fine needle aspiration biopsy (46.5%).
Subcutaneous or port site implantation after endoscopic thyroid surgery may occur in benign thyroid pathologies and therefore, oncologic principles must be strictly followed during surgery regardless of its histopathological nature.

BACKGROUND: Exposure to semi-volatile organic compounds (SVOCs) may link to thyroid nodule risk, but studies of mixed-SVOCs exposure effects are lacking. Traditional analytical methods are inadequate for dealing with mixed exposures, while machine learning (ML) seems to be a good way to fill the gaps in the field of environmental epidemiology research.
OBJECTIVE: Different ML algorithms were used to explore the relationship between mixed-SVOCs exposure and thyroid nodule.
METHODS: A 1:1:1 age- and gender-matched case-control study was conducted in which 96 serum SVOCs were measured in 50 papillary thyroid carcinoma (PTC), 50 nodular goiters (NG), and 50 controls. Different ML techniques such as Random Forest, AdaBoost were selected based on their predictive power, and variables were selected based on their weights in the models. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to assess the mixed effects of the SVOCs exposure on thyroid nodule.
RESULTS: Forty-three of 96 SVOCs with detection rate >80 % were included in the analysis. ML algorithms showed a consistent selection of SVOCs associated with thyroid nodule. Fluazifop-butyl and fenpropathrin are positively associated with PTC and NG in single compound models (all P < 0.05). WQS model shows that exposure to mixed-SVOCs was associated with an increased risk of PTC and NG, with the mixture dominated by fenpropathrin, followed by fluazifop-butyl and propham. In the BKMR model, mixtures showed a significant positive association with thyroid nodule risk at high exposure levels, and fluazifop-butyl showed positive effects associated with PTC and NG.
CONCLUSIONS: This study confirms the feasibility of ML methods for variable selection in high-dimensional complex data and showed that mixed exposure to SVOCs was associated with increased risk of PTC and NG. The observed association was primarily driven by fluazifop-butyl and fenpropathrin. The findings warranted further investigation.

OBJECTIVE: The purpose of this study is to inquire about the potential association between radiomics features and the pathological nature of thyroid nodules (TNs), and to propose an interpretable radiomics-based model for predicting the risk of malignant TN.
METHODS: In this retrospective study, computed tomography (CT) imaging and pathological data from 141 patients with TN were collected. The data were randomly stratified into a training group (n = 112) and a validation group (n = 29) at a ratio of 4:1. A total of 1316 radiomics features were extracted by using the pyradiomics tool. The redundant features were removed through correlation testing, and the least absolute shrinkage and selection operator (LASSO) or the minimum redundancy maximum relevance standard was used to select features. Finally, 4 different machine learning models (RF Hybrid Feature, SVM Hybrid Feature, RF, and LASSO) were constructed. The performance of the 4 models was evaluated using the receiver operating characteristic curve. The calibration curve, decision curve analysis, and SHapley Additive exPlanations method were used to evaluate or explain the best radiomics machine learning model.
RESULTS: The optimal radiomics model (RF Hybrid Feature model) demonstrated a relatively high degree of discrimination with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI, 0.70-0.97; P < 0.001) for the validation cohort. Compared with the commonly used LASSO model (AUC, 0.78; 95% CI, 0.60-0.91; P < 0.01), there is a significant improvement in AUC in the validation set, net reclassification improvement, 0.79 (95% CI, 0.13-1.46; P < 0.05), and integrated discrimination improvement, 0. 20 (95% CI, 0.10-0.30; P < 0.001).
CONCLUSIONS: The interpretable radiomics model based on CT performs well in predicting benign and malignant TNs by using quantitative radiomics features of the unilateral total thyroid. In addition, the data preprocessing method incorporating different layers of features has achieved excellent experimental results.
CONCLUSIONS: As the detection rate of TNs continues to increase, so does the diagnostic burden on radiologists. This study establishes a noninvasive, interpretable and accurate machine learning model to rapidly identify the nature of TN found in CT.

BACKGROUND: Combined thyroid fine-needle aspiration (FNA) cytology and valine-to-glutamate substitution at codon 600 of B-Raf proto-oncogene, serine/threonine kinase (BRAF V600E) mutation detection are procedures used for diagnosing thyroid nodules in many Chinese tertiary institutions. This retrospective study at our institution aimed to explore the effectiveness and challenges of the combined approach in diagnosing thyroid nodules and the correlation between BRAF V600E mutation status and behavior of papillary thyroid carcinoma.
METHODS: Thyroid FNA cytology and BRAF V600E mutation detection results were reviewed between November 2020 and July 2022. A total of 623 patients, each of whom underwent thyroidectomy and final pathological examination after FNA cytology diagnosis, were included in the study. The relationship between the BRAF V600E mutational status and pathological parameters was analyzed using the χ2 test. The effectiveness and challenges of FNA cytology alone and the combined procedure were also evaluated based on the final pathology.
RESULTS: Of 623 patients, 591 were diagnosed with papillary thyroid carcinoma (PTC), of which 456 were positive for the BRAF V600E mutation. It demonstrated near-perfect specificity for identifying PTC, and its incidence rate showed an age-specific curve with an inverted U-shaped distribution. The final pathological examination showed that the combined procedure had a higher sensitivity (83.91%) than FNA cytology alone (63.45%) for distinguishing PTC from other lesions (p < 0.001). Mutational status was associated with a larger maximum tumor diameter (p = 0.003) and a tendency of capsular invasion (p = 0.0542) but possibly unrelated to central lymph node metastasis (p = 0.1846). Nodular goiters accounted for most benign entities initially designated as Bethesda categories III-V.
CONCLUSIONS: BRAF V600E mutational analysis complements cytopathology and improves the PTC detection rate in FNA cytology samples due to the high prevalence of the mutation in China. BRAF V600E mutation does not show a statistical correlation with tumor aggressiveness. Morphological pitfalls such as histocyte aggregation, cystic-lining cells in nodular goiters, and oncocytes in Hashimoto\'s thyroiditis, were overwhelmingly found in BRAF V600E-negative specimens.

This study aimed to provide statistical data support for the development of thyroid phenotype-related follow-up and reference for follow-up duration and project selection by analyzing the clinical characteristics of thyroid phenotype in Pendred syndrome (PDS) based on multiple databases.
PDS-related pathogenic or possibly/pathogenic mutations were searched by Deafness Variation Database (DVD), ClinVar, and PubMed databases, the mutation sites were counted and the characteristics and thyroid phenotypes were analyzed.
The median age of hearing phenotype onset in PDS cases reported in multiple databases was 1.0 (1.0, 2.0) years, the median age of thyroid phenotype onset was 14.5 (5.8, 21.0) years, and the median age that thyroid phenotype was more delayed than hearing phenotype was 10.0 (4.0, 17.0) years. There were significant differences in the distribution of onset time between the two phenotypes (Z=-4.560, p<0.01). In these patients, the positive rates of goiter, thyroid nodules, abnormal thyroid function, and perchlorate discharge test (PDT) were 78%, 78%, 69%, and 78%, respectively. Moreover, the number of thyroid phenotype-positive items in the genotype group with frameshift mutation was not significantly higher than that in the group without frameshift mutation (Z=-1.452, p=0.147).
The early missed diagnosis of PDS may be due to the late onset of thyroid phenotype and the non-100% positive rate of examination items. Therefore, multi-item follow-up of the thyroid gland into adulthood will benefit patients. At present, the relationship between genotype and phenotype is still unclear, and prognosis cannot be determined according to genotype.

Pendrin (SLC26A4) is an anion exchanger expressed in the apical membranes of selected epithelia. Pendrin ablation causes Pendred syndrome, a genetic disorder associated with sensorineural hearing loss, hypothyroid goiter, and reduced blood pressure. However its molecular structure has remained unknown, limiting our understanding of the structural basis of transport. Here, we determine the cryo-electron microscopy structures of mouse pendrin with symmetric and asymmetric homodimer conformations. The asymmetric homodimer consists of one inward-facing protomer and the other outward-facing protomer, representing coincident uptake and secretion- a unique state of pendrin as an electroneutral exchanger. The multiple conformations presented here provide an inverted alternate-access mechanism for anion exchange. The structural and functional data presented here disclose the properties of an anion exchange cleft and help understand the importance of disease-associated variants, which will shed light on the pendrin exchange mechanism.

The intrapulmonary ectopic thyroid gland is exceedingly rare since the ectopic thyroid was discovered. Only eight cases have been reported in the worldwide literature. We present a case of multiple intrapulmonary ectopic thyroid glands with nodular goiter in a 10-year-old girl.
The girl was found with multiple intrapulmonary nodules in bilateral lungs during the treatment of nodular goiter. The intrapulmonary lesions were initially thought to be a high possibility of metastatic cancer. A computed tomography-guided percutaneous lung biopsy was performed, and the pathological examination confirmed that the diagnosis was ectopic intrapulmonary thyroid.
The ectopic intrapulmonary thyroid should be considered when children with nodular goiter presenting with suspected metastases in the lung.

Ectopic secretion of parathyroid hormone (PTH) is a rare cause of hypercalcemia in malignancy patients. A 56-year-old woman with life-threatening hypercalcemia was caused by poorly-differentiated endometrial carcinoma secreting PTH with concomitant nodular goiter mimic parathyroid tumors. The elevated level of PTH and calcium decreased immediately after cytoreductive surgery (CRS). The pathology confirmed mismatch repair (MMR)-deficient endometrial carcinoma with PTH expression. The patient received four-course chemotherapy and one-course immunotherapy after CRS. The disease progression led to multiple organ failure and death about five months after CRS. To our knowledge, this is the first case of hypercalcemia caused by MMR-deficient endometrial carcinoma with ectopic PTH secreting and the first report of malignancy associated hypercalcemia complicated with nodular goiter.

BACKGROUND: Nodular goiter is a common clinical problem, and thyroidectomy is preferred in patients with obstructive symptoms. Thyroidectomy is a complex procedure with some common complications. Three-dimensional (3D) computed tomography (CT) reconstruction and 3D printing provide visualized 3D anatomical structure, posing an enormously valuable potential in precise surgery with optimal efficacy and minimum complications. Here, we aimed to perform a precise thyroidectomy guided by this technology.
METHODS: The patient was an 80-year-old woman with 10 years of goiter, 1 year of labored dyspnea, and a history of thyroid surgery 62 years ago. In addition to ultrasonography examination, CT images were obtained to construct the 3D model to identify the 3D relationship between the lesion and adjacent structures, and a 3D model of the trachea was created and printed using a 3D printer.
RESULTS: The 3D model clearly presented the diffuse enlargement of the two lobes and isthmus and the compression of the goiter. Under the 3D guidance, the operative resection specimen of the right lobe and isthmus was 12 ´ 7 ´ 5 cm, whereas the left lobe specimen was 12 ´ 9 ´ 6 cm. Nodular goiter and lymphocytic thyroiditis were confirmed by postoperative histopathology. There were no complications after total thyroidectomy except for non-permanent hypocalcemia and hypoparathyroidism.
CONCLUSIONS: Our results proved that total thyroidectomy for giant goiter is challenging, and 3D image-guided thyroidectomy facilitates precise and safe resection with fewer complications. 3D CT reconstruction and 3D printing can provide anatomical details and may be considered in thyroidectomy planning for patients with giant goiter.