Nivolumab and Cabozantinib Immunotherapy Induced Thyroid Dysfunction Detected on 18 F-FDG PET/CT in Renal Cell Carcinoma.

ABSTRACT: Targeted immunotherapy became the most advanced approach for cancer treatment. Programmed death-1 (PD-1) expressed on activated T cells can reverse immune suppression and cause T-cell activation. Nivolumab, a PD-1 immune checkpoint inhibitor antibody that is a fully human immunoglobulin G4, blocks PD-1 and promotes antitumor immunity. Cabozantinib (tyrosine kinase inhibitor) inhibits the tyrosine kinase activity of vascular endothelial growth factor receptors 1, 2, and 3. As a result of enhancing immune response in normal tissues, immune-related adverse events can occur. Thyroid dysfunction is a common form of immune-related adverse event and seen on 18 F-FDG PET/CT scans post therapy.

Determining the frequency of thyroid involvement in chest CT scans of COVID-19 patients and its correlation with the severity of lung involvement and survival of patients in 2020.

Introduction: This study aimed to determine the frequency of thyroid gland involvement in chest CT scans of patients with COVID-19 admitted to university-affiliated hospitals and assess its relationship with the severity of lung involvement and patient survival in 2020. Material and methods: In this retrospective cross-sectional study, 1000 PCR-positive patients with COVID-19 who were referred to University-affiliated Hospital in 2020 and had chest CT performed within 72 hours of admission to the hospital were examined. The data was collected by patient file information and CT findings recorded in the PACS system, including thyroid involvement, the severity of lung involvement, and findings related to the death and recovery of patients. Results: The mean age of the examined patients was 56 years. 525 people (52.5%) were men, and 475 (47.5%) were women. 14% had severe pulmonary involvement, and 9.3% had very severe involvement. Moreover, 15.9 percent of them had deceased. 19.7% had focal thyroid involvement, 14% had diffuse involvement, and 66.3% were healthy subjects. Male gender and older age showed a significant relationship with thyroid gland involvement. The severity of lung involvement, the death rate in patients, and hospitalization in ICU were also significantly related to thyroid gland involvement in patients with COVID. Discussion and conclusion: This study highlights the importance of considering thyroid-gland involvement in the comprehensive management of COVID-19 patients. Routine screening and monitoring of thyroid-function may facilitate earlier detection and appropriate management of thyroid-related complications, potentially improving clinical outcomes. This study suggests that in COVID-19 infection the monitoring of thyroid function is prudent, particularly in cases of more serious disease.

Molecular imaging of thyroid and parathyroid diseases.

INTRODUCTION: Molecular imaging of thyroid and parathyroid diseases has changed in recent years due to the introduction of new radiopharmaceuticals and new imaging techniques. Accordingly, we provided an clinicians-oriented overview of such techniques and their indications. AREAS COVERED: A review of the literature was performed in the PubMed, Web of Science, and Scopus without time or language restrictions through the use of one or more fitting search criteria and terms as well as through screening of references in relevant selected papers. Literature up to and including December 2023 was included. Screening of titles/abstracts and removal of duplicates was performed and the full texts of the remaining potentially relevant articles were retrieved and reviewed. EXPERT OPINION: Thyroid and parathyroid scintigraphy remains integral in patients with thyrotoxicosis, thyroid nodules, differentiated thyroid cancer and, respectively, hyperparathyroidism. In the last years positron-emission tomography with different tracers emerged as a more accurate alternative in evaluating indeterminate thyroid nodules [18F-fluorodeoxyglucose (FDG)], differentiated thyroid cancer [124I-iodide, 18F-tetrafluoroborate, 18F-FDG] and hyperparathyroidism [18F-fluorocholine]. Other PET tracers are useful in evaluating relapsing/advanced forms of medullary thyroid cancer (18F-FDOPA) and selecting patients with advanced follicular and medullary thyroid cancers for theranostic treatments (68Ga/177Ga-somatostatin analogues).

Volumetric Ultrasound Imaging for the Whole Soft Tissue: Toward Enhanced Thyroid Disease Examination.

OBJECTIVES: Ultrasound imaging (USI) is the gold standard in the clinical diagnosis of thyroid diseases. Compared with two-dimensional (2D) USI, three-dimensional (3D) USI could provide more structural information. However, the unstable pressure generated by the hand-hold ultrasound probe scanning can cause tissue deformation, especially in soft tissues such as the thyroid. The deformation is manifested as tissue structure being compressed in 2D USI, which results in structural discontinuity in 3D USI. Furthermore, multiple scans apply pressure in different directions to the tissue, which will cause relative displacement between the 3D images obtained from multiple thyroid scans. METHODS: In this work, we proposed a framework to minimize the influence of the variation of pressure in thyroid 3D USI. To correct pressure artifacts in a single scanning sequence, an adaptive method to smooth the position of the 2D ultrasound (US) image sequence is adopted before performing volumetric reconstruction. To build a whole 3D US image including both sides of the thyroid gland, an iterative closest point (ICP) based registration pipeline is adopted to eliminate the relative displacement caused by different pressure directions. RESULTS: Our proposed method was validated by in vivo experiments, including healthy volunteers and volunteers with thyroid nodules at different grading levels. CONCLUSIONS: The thyroid gland and nodule are rendered intelligently in the whole scanning region to facilitate the observation of 3D USI results by the doctor. This work might make a positive contribution to the clinical diagnosis of diseases of the thyroid or other soft tissues.

Role of advanced MRI sequences for thyroid lesions assessment. A narrative review.

Despite not being the first imaging modality for thyroid gland assessment, Magnetic Resonance Imaging (MRI), thanks to its optimal tissue contrast and spatial resolution, has provided some advancements in detecting and characterizing thyroid abnormalities. Recent research has been focused on improving MRI sequences and employing advanced techniques for a more comprehensive understanding of thyroid pathology. Although not yet standard practice, advanced MRI sequences have shown high accuracy in preliminary studies, correlating well with histopathological results. They particularly show promise in determining malignancy risk in thyroid lesions, which may reduce the need for invasive procedures like biopsies. In this line, functional MRI sequences like Diffusion Weighted Imaging (DWI), Dynamic Contrast-Enhanced MRI (DCE-MRI), and Arterial Spin Labeling (ASL) have demonstrated their potential usefulness in evaluating both diffuse thyroid conditions and focal lesions. Multicompartmental DWI models, such as Intravoxel Incoherent Motion (IVIM) and Diffusion Kurtosis Imaging (DKI), and novel methods like Amide Proton Transfer (APT) imaging or artificial intelligence (AI)-based analyses are being explored for their potential valuable insights into thyroid diseases. This manuscript reviews the critical physical principles and technical requirements for optimal functional MRI sequences of the thyroid and assesses the clinical utility of each technique. It also considers future prospects in the context of advanced MR thyroid imaging and analyzes the current role of advanced MRI sequences in routine practice.

Evaluation of thyroid congestion in patients with heart failure using shear wave elastography: An observational study.

Shear wave elastography (SWE) is a noninvasive method for measuring organ stiffness. Liver stiffness measured using SWE reflects hepatic congestion in patients with heart failure (HF). However, little is known about the use of SWE to assess other organ congestions. This study aimed to evaluate the utility of SWE for assessing not only the liver but also thyroid congestion in patients with HF. This prospective study included 21 patients with HF who have normal thyroid lobes (age: 77.0 ±â€…11.0, men: 14). Thyroid and liver stiffness were measured by SWE using the ARIETTA 850 ultrasonography system (Fujifilm Ltd., Tokyo, Japan). SWE of the thyroid was performed on B-mode ultrasonography; a target region was identified within a region of interest. SWE was performed in each lobe of the thyroid gland. Five measurements were taken at the same location and the averages were recorded for comparison. We investigated the relationship between SWE for evaluating thyroid stiffness and the clinical characteristics of patients with HF. SWE of the thyroid was significantly correlated with SWE of the liver (R = 0.768, P < .001), thyroid stimulation hormone (R = 0.570, P = .011), free thyroxine (R = 0.493, P = .032), estimated right atrial pressure (RAP; R = 0.468, P = .033), and composite congestion score (R = 0.441, P = .045). SWE may be useful for evaluating thyroid stiffness and assessing the degree of thyroid congestion. Thyroid congestion may reflect the elevation of RAP and cause thyroid dysfunction through organ congestion.

Assessment of Thyroid Gland in Children with Point-of-Care Ultrasound (POCUS): Radiological Performance and Feasibility of Handheld Ultrasound in Clinical Practice

Objective: Point-of-Care Ultrasound (POCUS) refers to the use of portable ultrasound machines to perform quick and focused ultrasound examinations at a patient's bedside or point-of-care. POCUS can be performed by all health workers with specific training to use POCUS. The aim of this study was to investigate the radiological performance and feasibility of POCUS using a handheld ultrasound device (HHUSD) in children for examining the thyroid gland. Methods: A pediatric endocrinologist performed thyroid imaging in children referred to our hospital with suspected thyroid disease using an HHUSD. The same children underwent ultrasonography (US) imaging using the same device by the first radiologist, and a second radiologist performed thyroid US using an advanced high-range ultrasound device (AHUSD) (defined as the gold-standard method) within two hours. The data obtained by the three researchers were compared with each other. Results: This study included 105 patients [68.6% girls (n=72)] with a mean age 12.8±3.6 years. When the thyroid volume was evaluated, a strong correlation was found between the measurements of the three researchers (AA vs. MG: r=0.963, AA vs. GT: r=0.969, MG vs. GT: r=0.963, p<0.001). According to the Bland-Altman analysis for total thyroid volume, AA measured 0.43 cc [95% confidence interval (CI): -0.89-0.03] smaller than MG, and 0.11 cc (95% CI: -0.30-0.52) larger than GT, whereas MG measured 0.52 cc (95% CI: 0.09-0.94) larger than GT. When evaluated for the presence of goiter and nodules, a near-perfect agreement was found between the results of the three researchers (AA vs. GT; κ=0.863, MG vs. GT; κ=0.887, p<0.001, and AA vs. GT; κ=1.000, MG vs. GT; κ=0.972, p<0.001, respectively). When evaluated in terms of the longest axis of nodules, a high correlation was found between the measurements of the three researchers (AA vs. MG; r=0.993, AA vs. GT; r=0.996, MG vs. GT; r=0.996, p<0.001). When evaluated in terms of the final diagnosis, the evaluations of the three researchers showed excellent agreement with each other (AA vs. GT; κ=0.893, MG vs. GT; κ=0.863, p<0.001, accuracy rate AA vs. GT: 93.3%; MG vs. GT: 91.4%). Conclusion: A pediatric endocrinologist, equipped with sufficient training in thyroid US evaluation, incorporated HHUSD examination as a routine clinical tool in an outpatient setting. It was shown that, they could effectively assess normal thyroid tissue in pediatric patients. Moreover, the HHUSD proved to be useful in detecting thyroid pathologies. However, it is important to note that for a more comprehensive evaluation of thyroid nodules, including detailed assessment and Thyroid Imaging Reporting and Data System (TIRADS) classification, patients should be referred to radiology departments equipped with AHUSD systems. These specialized devices, along with the expertise of radiologists, are essential for in-depth evaluations and accurate classification of thyroid nodules.

[Review on ultrasonographic diagnosis of thyroid diseases based on deep learning].

In recent years, the incidence of thyroid diseases has increased significantly and ultrasound examination is the first choice for the diagnosis of thyroid diseases. At the same time, the level of medical image analysis based on deep learning has been rapidly improved. Ultrasonic image analysis has made a series of milestone breakthroughs, and deep learning algorithms have shown strong performance in the field of medical image segmentation and classification. This article first elaborates on the application of deep learning algorithms in thyroid ultrasound image segmentation, feature extraction, and classification differentiation. Secondly, it summarizes the algorithms for deep learning processing multimodal ultrasound images. Finally, it points out the problems in thyroid ultrasound image diagnosis at the current stage and looks forward to future development directions. This study can promote the application of deep learning in clinical ultrasound image diagnosis of thyroid, and provide reference for doctors to diagnose thyroid disease.

Diagnosis of thyroid disease using deep convolutional neural network models applied to thyroid scintigraphy images: a multicenter study.

Objectives: The aim of this study was to improve the diagnostic performance of nuclear medicine physicians using a deep convolutional neural network (DCNN) model and validate the results with two multicenter datasets for thyroid disease by analyzing clinical single-photon emission computed tomography (SPECT) image data. Methods: In this multicenter retrospective study, 3194 SPECT thyroid images were collected for model training (n=2067), internal validation (n=514) and external validation (n=613). First, four pretrained DCNN models (AlexNet, ShuffleNetV2, MobileNetV3 and ResNet-34) for were tested multiple medical image classification of thyroid disease types (i.e., Graves' disease, subacute thyroiditis, thyroid tumor and normal thyroid). The best performing model was then subjected to fivefold cross-validation to further assess its performance, and the diagnostic performance of this model was compared with that of junior and senior nuclear medicine physicians. Finally, class-specific attentional regions were visualized with attention heatmaps using gradient-weighted class activation mapping. Results: Each of the four pretrained neural networks attained an overall accuracy of more than 0.85 for the classification of SPECT thyroid images. The improved ResNet-34 model performed best, with an accuracy of 0.944. For the internal validation set, the ResNet-34 model showed higher accuracy (p < 0.001) when compared to that of the senior nuclear medicine physician, with an improvement of nearly 10%. Our model achieved an overall accuracy of 0.931 for the external dataset, a significantly higher accuracy than that of the senior physician (0.931 vs. 0.868, p < 0.001). Conclusion: The DCNN-based model performed well in terms of diagnosing thyroid scintillation images. The DCNN model showed higher sensitivity and greater specificity in identifying Graves' disease, subacute thyroiditis, and thyroid tumors compared to those of nuclear medicine physicians, illustrating the feasibility of deep learning models to improve the diagnostic efficiency for assisting clinicians.

The Role of Nuclear Medicine in Benign Thyroid Disease.

Since the mid-twentieth century, the radionuclide thyroid scan has been utilized in the management of benign thyroid disorders. In current medical practice, patients with hyperthyroidism are referred for thyroid scintigraphy, while patients with goiters and thyroid nodules are most often evaluated by ultrasound or computed tomography. Since thyroid scintigraphy reflects the functional state of the gland, it provides information that anatomical imaging lacks. Therefore, radionuclide imaging of the thyroid is the imaging modality of choice in the evaluation of the hyperthyroid patient. In addition, patients with so-called subclinical hyperthyroidism often present a diagnostic dilemma to the clinician since the causative factor must be determined for proper patient management. The aim of this manuscript is to illustrate the imaging characteristics of thyroid disorders commonly seen in clinical practice resulting in thyrotoxicosis or pending thyrotoxicosis, so that correlation with clinical presentation and pertinent laboratory data will lead to the correct diagnosis.

Consequences of early thyroid ultrasound on subsequent tests, morbidity and costs: an explorative analysis of routine health data from German ambulatory care.

OBJECTIVES: This study aims to evaluate whether the use of thyroid ultrasound (US) early in the work-up of suspected thyroid disorders triggers cascade effects of medical procedures and to analyse effects on morbidity, healthcare usage and costs. STUDY DESIGN: Retrospective analysis of claims data from ambulatory care (2012-2017). SETTING: Primary care in Bavaria, Germany, 13 million inhabitants. PARTICIPANTS: Patients having received a thyroid stimulating hormone (TSH) test were allocated to (1) observation group: TSH test followed by an early US within 28 days or (2) control group: TSH test, but no early US. Propensity score matching was used adjusting for socio-demographic characteristics, morbidity and symptom diagnosis (N=41 065 per group after matching). PRIMARY AND SECONDARY OUTCOME MEASURES: Using cluster analysis, groups were identified regarding frequency of follow-up TSH tests and/or US and compared. RESULTS: Four subgroups were identified: cluster 1: 22.8% of patients, mean (M)=1.6 TSH tests; cluster 2: 16.6% of patients, M=4.7 TSH tests; cluster 3: 54.4% of patients, M=3.3 TSH tests, 1.8 US; cluster 4: 6.2% of patients, M=10.9 TSH tests, 3.9 US. Overall, reasons that explain the tests could rarely be found. An early US was mostly found in clusters 3 and 4 (83.2% and 76.1%, respectively, were part of the observation group). In cluster 4 there were more women, thyroid-specific morbidity and costs were higher and the early US was more likely to be performed by specialists in nuclear medicine or radiologists. CONCLUSION: Presumably unnecessary tests in the field of suspected thyroid diseases seem to be frequent, contributing to cascades effects. Neither German nor international guidelines provide clear recommendations for or against US screening. Therefore, guidelines on when to apply US and when not are urgently needed.

Ultrasound findings of the thyroid gland in children and adolescents.

Ultrasonography (US) is an important diagnostic tool in evaluating thyroid diseases in pediatric patients. This pictorial essay reviews the application of various ultrasound techniques such as B-Mode ultrasound and color Doppler, elastography and contrast enhanced ultrasound (CEUS) in children and adolescents in various thyroid pathologies including congenital thyroid abnormalities, diffuse thyroid diseases (DTD), focal thyroid lesions and thyroid malignancy.

Significance of FDG-PET standardized uptake values in predicting thyroid disease.

Objective: This study aimed to determine a standardized cut-off value for abnormal 18F-fluorodeoxyglucose (FDG) accumulation in the thyroid gland. Methods: Herein, 7013 FDG-PET/CT scans were included. An automatic thyroid segmentation method using two U-nets (2D- and 3D-U-net) was constructed; mean FDG standardized uptake value (SUV), CT value, and volume of the thyroid gland were obtained from each participant. The values were categorized by thyroid function into three groups based on serum thyroid-stimulating hormone levels. Thyroid function and mean SUV with increments of 1 were analyzed, and risk for thyroid dysfunction was calculated. Thyroid dysfunction detection ability was examined using a machine learning method (LightGBM, Microsoft) with age, sex, height, weight, CT value, volume, and mean SUV as explanatory variables. Results: Mean SUV was significantly higher in females with hypothyroidism. Almost 98.9% of participants in the normal group had mean SUV < 2 and 93.8% participants with mean SUV < 2 had normal thyroid function. The hypothyroidism group had more cases with mean SUV ≥ 2. The relative risk of having abnormal thyroid function was 4.6 with mean SUV ≥ 2. The sensitivity and specificity for detecting thyroid dysfunction using LightGBM (Microsoft) were 14.5 and 99%, respectively. Conclusions: Mean SUV ≥ 2 was strongly associated with abnormal thyroid function in this large cohort, indicating that mean SUV with FDG-PET/CT can be used as a criterion for thyroid evaluation. Preliminarily, this study shows the potential utility of detecting thyroid dysfunction based on imaging findings.

Review on ultrasonographic diagnosis of thyroid diseases based on deep learning / 生物医学工程学杂志

In recent years, the incidence of thyroid diseases has increased significantly and ultrasound examination is the first choice for the diagnosis of thyroid diseases. At the same time, the level of medical image analysis based on deep learning has been rapidly improved. Ultrasonic image analysis has made a series of milestone breakthroughs, and deep learning algorithms have shown strong performance in the field of medical image segmentation and classification. This article first elaborates on the application of deep learning algorithms in thyroid ultrasound image segmentation, feature extraction, and classification differentiation. Secondly, it summarizes the algorithms for deep learning processing multimodal ultrasound images. Finally, it points out the problems in thyroid ultrasound image diagnosis at the current stage and looks forward to future development directions. This study can promote the application of deep learning in clinical ultrasound image diagnosis of thyroid, and provide reference for doctors to diagnose thyroid disease.

New insights into thyroid dysfunction in patients with inactivating parathyroid hormone/parathyroid hormone-related protein signalling disorder (the hormonal and ultrasound aspects): One-centre preliminary results.

Objective: This study aimed to present the spectrum of thyroid dysfunction, including hormonal and ultrasound aspects, in a cohort of paediatric and adult patients diagnosed with inactivating parathyroid hormone (PTH)/PTH-related protein signalling disorders 2 and 3 (iPPSD). Methods: The medical records of 31 patients from 14 families diagnosed with iPPSD between 1980 and 2021 in a single tertiary unit were retrospectively analysed. Biochemical, hormonal, molecular, and ultrasonographic parameters were assessed. Results: In total, 28 patients from 13 families were diagnosed with iPPSD2 (previously pseudohypoparathyroidism [PHP], PHP1A, and pseudo-PHP) at a mean age of 12.2 years (ranging from infancy to 48 years), and three patients from one family were diagnosed with iPPSD3 (PHP1B). Thyroid dysfunction was diagnosed in 21 of the 28 (75%) patients with iPPSD2. Neonatal screening detected congenital hypothyroidism (CH) in 4 of the 20 (20%) newborns. The spectrum of thyroid dysfunction included: CH, 3/21 (14.2%); CH and autoimmune thyroiditis with nodular goitre, 1/21 (4.8%); subclinical hypothyroidism, 10/21 (47.6%); subclinical hypothyroidism and nodular goitre, 1/21 (4.8%); primary hypothyroidism, 4/21 (19%); and autoimmune thyroiditis (Hashimoto and Graves' disease), 2/21 (9.6%). Thyroid function was normal in 7 of the 28 (25%) patients with iPPSD2 and in all patients with iPPSD3. Ultrasound evaluation of the thyroid gland revealed markedly inhomogeneous echogenicity and structure in all patients with thyroid dysfunction. Goitre was found in three patients. Conclusion: The spectrum of thyroid dysfunction in iPPSD ranges from CH to autoimmune thyroiditis and nodular goitre. Ultrasonography of the thyroid gland may reveal an abnormal thyroid parenchyma.