Benign thyroid nodules are significantly common and occur in 50-60% of the population. Therefore, differentiation from malignant nodes and the choice of treatment tactics in some cases of benign pathology remain relevant. Despite advances in the clinical evaluation of thyroid nodules, methodological challenges exist due to empirically simplistic understandings of the nodular process. Different opinions on the pathogenesis of thyroid nodules and the history of the formation of the idea of ​​the stages of nodules are considered. For the first time, based on natural principles and many years of ultrasound analysis of changes in benign thyroid nodules, three stages of the nodular process were identified: Development, Wasting and Scarring. The stage of exhaustion has three substages: Initial, Moderate and Significant Wasting. The principles of stage-by-stage changes in nodules are explained and their ultrasound signs are shown. The key principle of the stages of nodules is the ratio of the magnitudes of the processes of regeneration (proliferation) and destruction in the nodule. Separate stage changes may occur in node segments. In such cases, part of the segments may show signs of the Development stage, another part-Wasting, and the third part-Scarring. The different variants of thyroid nodules are explained in terms of stages. Practical recommendations for differentiating ultrasound signs of nodules associated with stages are proposed. Knowledge about the staged changes in thyroid nodules helps reduce the likelihood of diagnostic errors, better navigate the prognosis and choice of treatment tactics, and recommend preventive ultrasound examination of the thyroid.

BACKGROUND: Over the past millennia, the evaluation and management of thyroid nodules has essentially remained the same with thyroidectomy as the only reliable method to identify malignancy. However, in the last 30 years, technological advances have significantly improved diagnostic management of thyroid nodules. Advances in imaging have allowed development of a reliable risk- based stratification system to identify nodules at increased risk of malignancy. At the same time, sensitive imaging has caused collateral damage to the degree that we are now identifying and treating many small, low risk nodules with little to no clinical relevance.
OBJECTIVE: To review the history of thyroid nodule evaluation with emphasis on recent changes and future pathways.
METHODS: Literature review and discussion.
RESULTS: Thyroid ultrasound remains the best initial method to evaluate the thyroid gland for nodules. Different risk-of-malignancy protocols have been developed and introduced by different societies, reporting methods have been developed and improved each, with goals of improving the ability to recognize nodules requiring further intervention and minimizing excessive monitoring of those who do not. Once identified, cytological evaluation of nodules further enhances malignancy identification with molecular markers assisting in ruling out malignancies in indeterminate nodules preventing unneeded intervention. And all societies have urged avoidance of overdiagnosis and overtreatment of low-risk cancers of little to no clinical relevance.
CONCLUSIONS: In this review, we describe advancements in nodule evaluation and management, while emphasizing caution in overdiagnosing and overtreating low-risk lesions without clinical importance.

UNASSIGNED: Fine needle aspiration (FNA) is the gold standard method recommended in the diagnosis of thyroid nodules. Bethesda IV cytology results are identified in 7-9% of nodules investigated through FNA, with reported malignancy rate in a wide range of 10-40%. The recommended treatment is either surgical or risk additional molecular testing before surgery. However, a large number of nodules belonging to this category (60-80%) are observed to be benign after surgical excision, which can put the patient at risk of unnecessary surgical morbidity. This study aimed to assess the diagnostic performance of conventional ultrasound, the ACR TI-RADS score and elastography in cases of Bethesda IV cytology on FNA.
UNASSIGNED: We evaluated ninety-seven consecutive cases with Bethesda category IV results on FNA by using conventional B-mode ultrasound, qualitative strain or shear-wave elastography (Hitachi Preirus Machine, Hitachi Inc., Japan and Aixplorer Mach 30 Supersonic Imagine, Aix-en-Provence, France) and all nodules were classified according to the ACR TI-RADS system. Conventional ultrasound was used to categorize the nodules as potentially malignant based on the following features: hypoechogenicity, inhomogeneity, a taller than wide shape, irregular margins, presence of microcalcifications, an interrupted thyroid capsule and suspicious cervical lymph nodes. Elastography classified nodules with increased stiffness as suspicious for malignancy.
UNASSIGNED: We considered pathology results as the gold standard diagnosis, finding that 32 out of 97 nodules were carcinomas (33%) and 65 out of 97 were benign nodules (67%). The benign group included twenty cases of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Finally, we compared ultrasound data with pathology results, which showed that nineteen out of the 32 malignant nodules presented with increased stiffness on elastography (p=0.0002). On conventional ultrasound, we found that microcalcifications (p=0.007), hypoechogenicity and irregular margins (p=0.006) are features which can distinguish between benign and malignant nodules with statistical significance.
UNASSIGNED: Integrating elastography as a parameter of the ACR TI-RADS score in the evaluation of Bethesda category IV nodules showed a sensitivity of 90.62% in detecting thyroid cancer cases (p=0.006). We can conclude that elastographic stiffness as an addition to high risk features observed on conventional ultrasound improves the detection of malignant nodules in cases with Bethesda IV cytology.

The present report describes for the first time a case of diffuse hyperthyroidism in a 30-year-old female patient who had normal levels of thyroid-stimulating hormone receptor antibodies (TSHR-Ab), slightly elevated plasma levels of thyroid hormones, and slightly increased thyroid blood flow. Seven years before, after severe stress, she had Graves\' disease with elevated plasma levels of TSHR-Ab. The patient\'s recent medical history included mental stress and autonomic dysfunction. This report describes a mild form of hyperthyroidism in terms of elevated plasma levels of thyroid hormones and Doppler ultrasonography data; this condition was first defined as \'minor hyperthyroidism\'. The examination data suggest a probable secondary role of the immune system and primary role of the autonomic nervous system in the pathogenesis of Graves\' disease.

Ultrasound can identify important characteristics in primary hypothyroidism and diffuse hyperthyroidism (Graves\' disease). Therefore, sonologists are actively investigating ultrasound criteria to differentiate between these two conditions. Nevertheless, practice shows the absence of such ultrasonic landmarks. For the first time in the literature, three cases of primary hypothyroidism have demonstrated an ultrasound pattern identical to that of Graves\' disease. This pattern includes the presence of goiter, marked total hypoechogenicity of the parenchyma, significantly or moderately increased blood flow intensity (\'thyroid inferno\'), and elevated peak systolic velocity of the superior thyroid arteries. These signs are less common in hypothyroidism compared to hyperthyroidism. Diagnostic data suggest that the pathogeneses of primary hypothyroidism and Graves\' disease share the same mechanisms, leading to similar thyroid ultrasound patterns. One of these shared mechanisms is presumably thyroid overstimulation by the autonomic nervous system, which is adequate to the body\'s hormonal requirements in hypothyroidism but excessive in hyperthyroidism.

Background  Many different risk stratification systems have been formulated for thyroid nodules, differing in their fine-needle aspiration cytology (FNAC) indication, suggesting a lack of consensus around the world. Purpose  This prospective study was conducted to find the best guideline for risk stratification, for a better malignancy yield, and with reduced rates of negative FNACs among three Thyroid Imaging, Reporting, and Data System (TIRADS) guidelines. Materials and Methods  A total of 625 thyroid nodules with conclusive FNAC or histopathological diagnosis were included in the study. Various sonographic parameters were recorded. They were classified into categories as per the three guidelines and compared with FNAC diagnosis. The guidelines were evaluated in terms of sensitivity, specificity, predictive values, and diagnostic accuracy. Sensitivity and specificity were compared by McNemar\'s test. Results  American College of Radiology (ACR) TIRADS had the highest diagnostic accuracy (56.8%), specificity (50.75%), positive predictive value (23.92%), lowest rates of negative FNACs (76.08%), and high negative predictive value (97.84 %). Korean (K) TIRADS had the maximum sensitivity (97.75%), highest negative predictive value (98.44%), and gross malignancy yield. European TIRADS was between the two other guidelines in most parameters with specificity like K TIRADS. Conclusion  All the three guidelines are very good screening tools, with comparable high sensitivity. ACR TIRADS is better in terms of specificity and reduced rates of negative FNACs. Including the presence of a suspicious cervical lymph node as a criterion and more frequent follow-up might further improve the diagnostic performance of the guideline.

For different thyroid diseases and hormonal metabolism, ultrasound (US) of the thyroid gland reveals hypoechogenicity. Despite the direct correlation of hypoechogenicity with the levels of thyroid-stimulating hormone and antibodies of thyroid peroxidase and thyroglobulin, ~20% of this correlation is inconsistent, thus restricting the comprehensive utilisation of this valuable diagnostic sign. Thus, it is necessary to investigate the additional circumstances affecting the extent and features of the US hypoechogenicity of the thyroid gland. The technique for assessing thyroid hypoechogenicity was based on the basic setting of the US mode and visual assessment in percentage of gray relative to a gradient gray scale. Doppler mode was used. US data were compared with the results of hormonal and immune blood tests. The study contains the morphofunctional basis of the various US hypoechogenicities detected in the diffuse pathology of the thyroid gland has been presented, and the principles and probable mechanisms of widespread and segmental hypoechogenicity formation are disclosed for the first time. Furthermore, a mandatory Doppler involving thyroid parenchyma blood flow intensity and peak systolic blood velocity of thyroid arteries, which indicates the magnitude of neurovegetative influence, has been suggested. The results of the study shows revealed that the evaluation of the importance and features of US hypoechogenicity in various diffuse thyroid pathologies is probably based on a single system involving neurohumoral regulation, segmental arrangement and compensatory reserve state of the gland parenchyma.

OBJECTIVE: Ultrasound evaluation of thyroid nodules is the preferred technique, but it is dependent on operator interpretation, leading to inter-observer variability. The current study aimed to determine the inter-physician consensus on nodular characteristics, risk categorization in the classification systems, and the need for fine needle aspiration puncture.
METHODS: Four endocrinologists from the same center blindly evaluated 100 ultrasound images of thyroid nodules from 100 different patients. The following ultrasound features were evaluated: composition, echogenicity, margins, calcifications, and microcalcifications. Nodules were also classified according to ATA, EU-TIRADS, K-TIRADS, and ACR-TIRADS classifications. Krippendorff\'s alpha test was used to assess interobserver agreement.
RESULTS: The interobserver agreement for ultrasound features was: Krippendorff\'s coefficient 0.80 (0.71-0.89) for composition, 0.59 (0.47-0.72) for echogenicity, 0.73 (0.57-0.88) for margins, 0.55 (0.40-0.69) for calcifications, and 0.50 (0.34-0.67) for microcalcifications. The concordance for the classification systems was 0.7 (0.61-0.80) for ATA, 0.63 (0.54-0.73) for EU-TIRADS, 0.64 (0.55-0.73) for K-TIRADS, and 0.68 (0.60-0.77) for K-TIRADS. The concordance in the indication of fine needle aspiration puncture (FNA) was 0.86 (0.71-1), 0.80 (0.71-0.88), 0.77 0.67-0.87), and 0.73 (0.64-0.83) for systems previously described respectively.
CONCLUSIONS: Interobserver agreement was acceptable for the identification of nodules requiring cytologic study using various classification systems. However, limited concordance was observed in risk stratification and many ultrasonographic characteristics of the nodules.

OBJECTIVE: To assess the bedside utility of Spectral Doppler Ultrasound (SDUS) in the initial evaluation of patients presenting with thyrotoxicosis.
METHODS: This is a retrospective cross-sectional study of patients diagnosed with thyrotoxicosis at an academic outpatient endocrinology clinic from August 2019 to November 2022. The thyroid arteries\' peak systolic velocities (PSV) were measured bilaterally using SDUS. PSV ≥40 cm/s in at least a single thyroid artery was considered a reasonable cut-off for Graves\' disease and PSV of perinodular artery ≥ 25 cm/s for toxic adenoma.
RESULTS: We identified 73 patients. Mean age ± standard deviation 45.2 ± 16.4 years, 54 (74.0%) were female, 49 (67.1%) were Caucasian, 23 (31.5%) were African American, and 1 (1.4%) was Asian. The confirmed diagnoses were 48 (65.8%) Graves\' disease, 13 (17.8%) thyroiditis, four (5.5%) toxic adenoma, four (5.5%) amiodarone-induced thyroiditis type 2, 1 (1.4%) toxic multinodular goiter, 1 (1.4%) had an unremarkable repeat thyroid function testing, and two (2.7%) were unconfirmed. Diagnosis based on the SDUS initial assessment was accurate in 65 (89.0%) of the patients, and it was conclusive and confirmatory during the initial encounter in 55 (75.3%) of the patients before additional testing. A thyroid scan was obtained in nine (12.3%) patients. Incorrectly diagnosed patients were observed in two patients of each of the following categories: Graves\' disease, thyroiditis, toxic adenoma, and unconfirmed diagnoses.
CONCLUSIONS: SDUS can be a valuable, efficient, and cost-effective bedside tool in the initial assessment of patients presenting with thyrotoxicosis.

Hyperthyroidismis a prevalent condition affecting global populations, with an overall prevalence of 1.2%. Our research aimed to establish a systematic diagnostic approach using multiparametric ultrasound (MPUS) to diagnose hyperthyroid diffuse thyroid disease (DTD).
We conducted a retrospective study from June 2021 to June 2023 at a specialized endocrinology center in Timisoara, Romania, enrolling subjects presenting with clinical hyperthyroidism. Using the Mach 30 Aixplorer ultrasound equipment, evaluations were performed initially in B-mode US, followed by Color Doppler and Spectral Doppler measurements, and finally, 2D Shear wave elastography (SWE).
From the 218 patients analyzed, the diagnosis of DTD with hyperthyroidism was confirmed through biochemical assessment, subgrouping various pathologies such as subacute thyroiditis, Graves\' disease, painless thyroiditis, Hashimoto\'s thyroiditis, iatrogenic, as well as healthy controls. In the first step, B-mode hypoechogenicity had an AUC of 0.951 for DTD detection. In the second step, the peak systolic velocity differentiated Graves\' disease with a median of 42.4 cm/s and an AUC of 1. Lastly, the third step consisted of SWE evaluation, revealing a mean elasticity index in the SAT subgroup significantly higher from other subgroups (p<0.001) with an AUC of 1.
Our study offers a step-by-step evaluation algorithm for DTD diagnosis, with a very good overall diagnostic performance (AUC of 0.946).