Thyroid Nodules Research Articles

Machine Learning Streamlines the Morphometric Characterization and Multiclass Segmentation of Nuclei in Different Follicular Thyroid Lesions: Everything in a NUTSHELL

The diagnostic assessment of thyroid nodules is hampered by the persistence of uncertainty in borderline cases and further complicated by the inclusion of noninvasive follicular tumor with papillary-like nuclear features (NIFTP) as a less aggressive alternative to papillary thyroid carcinoma (PTC). In this setting, computational methods might facilitate the diagnostic process by unmasking key nuclear characteristics of NIFTP. The main aims of this work were to (1) identify morphometric features of NIFTP and PTC that are interpretable for the human eye and (2) develop a deep learning model for multiclass segmentation as a support tool to reduce diagnostic variability. Our findings confirmed that nuclei in NIFTP and PTC share multiple characteristics, setting them apart from hyperplastic nodules (HP). The morphometric analysis identified 15 features that can be translated into nuclear alterations readily understandable by pathologists, such as a remarkable internuclear homogeneity for HP in contrast to a major complexity in the chromatin texture of NIFTP and to the peculiar pattern of nuclear texture variability of PTC. A few NIFTP cases with available next-generation sequencing data were also analyzed to initially explore the impact of RAS-related mutations on nuclear morphometry. Finally, a pixel-based deep learning model was trained and tested on whole-slide images of NIFTP, PTC, and HP cases. The model, named NUTSHELL (NUclei from Thyroid tumors Segmentation to Highlight Encapsulated Low-malignant Lesions), successfully detected and classified the majority of nuclei in all whole-slide image tiles, showing comparable results with already well-established pathology nuclear scores. NUTSHELL provides an immediate overview of NIFTP areas and can be used to detect microfoci of PTC within extensive glandular samples or identify lymph node metastases. NUTSHELL can be run inside WSInfer with an easy rendering in QuPath, thus facilitating the democratization of digital pathology.

The Correlation Study on Ultrasonography, Fine Needle Aspiration Cytology, and Molecular Testing in Management of Thyroid Nodules

The Correlation Study on Ultrasonography, Fine Needle Aspiration Cytology, and Molecular Testing in Management of Thyroid Nodules

Cytomorphological Features for Fine Needle Aspiration of Thyroid Nodules Post Radioactive Iodine Treatment

Cytomorphological Features for Fine Needle Aspiration of Thyroid Nodules Post Radioactive Iodine Treatment

PTEN-related Thyroid Nodules in Pediatric Population: A Retrospective Cytology-Histology Study in a Single Institution

PTEN-related Thyroid Nodules in Pediatric Population: A Retrospective Cytology-Histology Study in a Single Institution

Diagnosing and management of thyroid nodules and goiter - current perspectives.

Due to the frequent diagnosis of benign thyroid nodules, it is necessary to deviate from the traditional paradigm based on frequent surgical treatment. This article highlights the evolution of diagnosis and treatment in recent years, beginning from standardization of ultrasound assessment of nodules and cytology results to minimally invasive techniques to reduce the size of symptomatic thyroid nodules. These achievements reduce the number of surgeries, enable more individualized care for patients with benign thyroid disease, reduce long-term complications, and promote cost-effectiveness within healthcare systems. Furthermore, although the use of minimally invasive techniques significantly decreases thyroid nodule volume, the thyroid nodule usually does not disappear and the challenges in this field are discussed (the efficacy of thermal ablation, a variable part of thyroid nodules that remains viable after thermal ablation, some of the nodules treated with thermal ablation may require a second treatment over time and the efficacy of thermal ablation in nodules with different phenotypes). However, although surgery still represents the "gold standard" for establishing the final histopathologic diagnosis, it is associated with lifelong thyroid hormone substitution need and serious complications in rare cases. Therefore, it should represent the ultima ratio only after a detailed diagnostic procedure. In the future, artificial intelligence-assisted programs for the evaluation and management of nodules are expected.

Diagnostic yield of combined ACR TI-RADS and Sonoelastography in solid thyroid nodules in tertiary care center: A prospective cross-sectional Study

Background: Thyroid nodules are prevalent, and accurate differentiation between benign and malignant nodules is crucial for management. We aim to evaluate the effectiveness of combining Thyroid Imaging Reporting and Data System (TIRADS) scoring with strain elastography, specifically the Elasticity Contrast Index (ECI), to differentiate between benign and malignant thyroid nodules. Methods: This analytical cross-sectional study involved 77 patients with solid thyroid nodules identified through B-mode ultrasonography. ACR TI-RADS scores, ECI values, and combined scores were compared with Fine needle aspiration Cytology (FNAC) results. Statistical analysis was performed using SPSS, and Pearson correlation tests were conducted to assess the correlation with FNAC findings. Result: The TI-RADS scoring system has a sensitivity of 83.3%, a specificity of 66.1%, and a positive predictive value of 42.9% for distinguishing benign and malignant nodules. Strain elastography with ECI values has a sensitivity of 94.4%, specificity of 98.3%, PPV of 94.4%, and NPV of 98.3%. Combining ACR TI-RADS and strain elastography achieves a sensitivity of 100%, specificity of 66.1%, NPV of 100%, and PPV of 47.4%. Conclusion: The study emphasizes the benefits of integrating noninvasive methods like ultrasound elastography and ACR TI-RADS for improved diagnostic precision, minimizing invasion and patient discomfort. This strategy is particularly advantageous for TI-RADS 3 nodules and reduces unnecessary procedures. However, FNAC should be reasonable and validated for higher classifications.

The Impact of Exposure to Iodine and Fluorine in Drinking Water on Thyroid Health and Intelligence in School-Age Children: A Cross-Sectional Investigation.

Iodine and fluorine, as halogen elements, are often coexisting in water environments, with nearly 200 million people suffering from fluorosis globally, and, in 11 countries and territories, adolescents have iodine intakes higher than that required for the prevention of iodine deficiency disorders. It has been suggested that excess iodine and/or fluorine can affect thyroid health and intellectual development, especially in children, but their combined effect has been less studied in this population. This study investigated 399 school-age children in Tianjin, China, collected drinking water samples from areas where the school-age children lived, and grouped the respondents according to iodine and fluorine levels. Thyroid health was measured using thyroid hormone levels, thyroid volume, and the presence of thyroid nodules; intelligence quotient (IQ) was assessed using the Raven's Progressive Matrices (CRT) test; and monoamine neurotransmitter levels were used to explore the potential relationship between thyroid health and intelligence. Multiple linear regression and restricted cubic spline (RCS) analyses showed that iodine and fluorine were positively correlated with thyroid volume and the incidence of thyroid nodules in school-age children, and negatively correlated with IQ; similar results were obtained in the secondary subgroups based on urinary iodine and urinary fluoride levels. Interaction analyses revealed a synergistic effect of iodine and fluorine. A pathway analysis showed that iodine and fluorine were negatively associated with the secretion of free triiodothyronine (FT3) and free tetraiodothyronine (FT4), which in turn were negatively associated with the secretion of thyroid-stimulating hormone (TSH). Iodine and fluorine may affect IQ in school-aged children through the above pathways that affect thyroid hormone secretion; of these, FT3 and TSH were negatively correlated with IQ, whereas FT4 was positively correlated with IQ. The relationship between thyroid hormones and monoamine neurotransmitters may involve the hypothalamic-pituitary-thyroid axis, with FT4 hormone concentrations positively correlating with dopamine (DA), norepinephrine (NE), and 5-hydroxytryptophan (5-HT) concentrations, and FT3 hormone concentrations positively correlating with DA concentrations. Monoamine neurotransmitters may play a mediating role in the effects of iodine and fluoride on intelligence in schoolchildren. However, this study has some limitations, as the data were derived from a cross-sectional study in Tianjin, China, and no attention was paid to the reciprocal effects of iodine and fluorine at different doses on thyroid health and intelligence in schoolchildren in other regions.

Cervical plexus block enhanced pain control for unilateral thermal ablation of thyroid nodules.

Despite being minimally invasive, thermal ablation (TA) of thyroid nodules may still cause significant pain during and shortly afterwards. Conventional analgesia relies on perithyroidal local anesthesia (PLA) with or without sedation. The use of cervical plexus block (CPB) has been extensively studied in thyroidectomy, but never studied in TA of the thyroid gland. This study examined whether adding ultrasound-guided CPB to PLA and sedation could further reduce post-operative pain in unilateral TA of thyroid nodules. Consecutive patients aged ≥18 years undergoing unilateral radiofrequency ablation (RFA) or microwave ablation (MWA) of thyroid nodules were reviewed. Group I patients did not receive CPB, and Group II patients received CPB by bupivacaine injection between the sternocleidomastoid muscle (SCM) and prevertebral fascia on the treatment side. Pain was charted immediately and 4 hours after ablation using a numeric rating scale (NRS) of 0-10. The Quality-of-Recovery-9 (QoR9) questionnaire was completed. Over an 18-month period, 100 patients underwent unilateral thyroid ablation (Group I, n=50; Group II, n=50). Comparable baseline patient demographics, nodule characteristics, ablation parameters were noted (P>0.05). Significantly lower immediate NRS {1 [0-3] vs. 4 [1.3-6], P<0.001}, 4-hour NRS {1 [0-3] vs. 2 [0-4], P=0.04}, and more zero immediate NRS (44% vs. 14%, P=0.001) was observed in Group II. Total QoR9 scores were comparable {16 [12-17] vs. 15 [12-17], P=0.72}. No adverse events occurred. All patients were discharged within the same day. Adding ultrasound-guided CPB further enhanced pain control following unilateral TA of thyroid nodules, without compromising quality of recovery or same-day discharge.

Evaluating the Diagnostic Role of ACR-TIRADS and Bethesda Classifications in Thyroid Nodules Highlighted by Cyto-Histopathological Studies.

To evaluate the accuracy of thyroid imaging reporting and data system (ACR-TIRADS) and the Bethesda system for reporting cytopathology (TBSRCP) classifications for identifying or ruling out thyroid malignancy in relation to the gold standard (post-surgical pathology). This cross-sectional study included 573 patients with single or multiple thyroid nodules. Patients were evaluated using the TIRADS and the TBSRCP classification. The data from a cohort of patients who underwent surgery (77/573, 13.4%) were correlated with post-operative pathology and the relevant clinical features of the patients. Of 573 patients, 545 (95.1%) were euthyroid, 24 (4.1%) were hypothyroid, and 4 (0.8%) were hyperthyroid; 419 (73.1%) had benign nodules (Bethesda II), 115 (20.1%) had intermediate (Bethesda III, IV), and 39 (6.8%) had Bethesda V and VI nodules. Four-hundred twenty (73.3%) patients were categorized as TIRADS 2,3, and 153 (26.7%) were categorized as TIRADS 4,5. The Bethesda and TIRADS classifications concorded significantly in thyroid nodule diagnosis (K=14.9%, P<0.001).Thyroid malignancy was significantly associated with microcalcification and interrupted halo, while benign nodules were significantly associated with macrocalcification and complete halo type (P=0.041, P=0.005, respectively). The TBSRCP could significantly detect malignant thyroid nodules with a sensitivity, specificity, PPV, and NPV of 64.1%, 98.1%, 85.0%, and 94.1%, respectively (K=88.2%, P<0.001), while the respective values for the TIRADS classification were 63.5%, 76.0%, 84.6%, and 50.0% (K=34.8%, P=0.001). The TIRADS and TBSRCP are essential primary steps for evaluating thyroid nodules and both are complimentary. Hence, each patient with thyroid nodules should be evaluated by both approaches before opting for surgery. Highly suspicious TIRADS categories TR4 and TR5 need further evaluation by fine needle aspiration cytology.

Risk factors for recurrent laryngeal nerve injury in microwave ablation of thyroid nodules: A multicenter study

Background and purposeThis study aimed to investigate the risk factors for recurrent laryngeal nerve (RLN) injury after microwave ablation (MWA) of thyroid nodules and to identify factors influencing the recovery time of post-procedure hoarseness. Materials and methodsWe retrospectively analyzed data from patients who underwent MWA for thyroid nodules at five hospitals between November 2018 and July 2022. Patients were divided into malignant and benign nodule groups. Variables analyzed included nodule size and location, the shortest distance from nodules to the thyroid capsule and tracheoesophageal groove (TEG-D), and ablation parameters. Univariate and multivariate analyses were performed to identify risk factors. Kaplan-Meier and Cox analyses were used to evaluate the recovery time of hoarseness after MWA. ResultsThe study included 1,216 patients (mean age 44 ± 12 [SD] years; 901 women) with 602 malignant nodules and 614 benign nodules. The posterior capsule distance (PCD) and TEG-D were identified as independent influencing factors for hoarseness in all patients (P = 0.014, OR = 0.068; P < 0.001, OR = 0.005; AUC = 0.869). TEG-D was a significant risk factor for hoarseness, with safe thresholds identified at 4.9 mm for malignant nodules and 2.2 mm for benign nodules. Among patients who developed hoarseness, those in the close-distance group (TEG-D≤2 mm) had a longer recovery time compared to the distant-distance group. TEG-D was an independent factor influencing recovery time (P = 0.008, HR = 11.204). ConclusionClinicians should consider several factors, particularly TEG-D and PCD, when assessing the risk of RLN injury before MWA. TEG-D was a vital independent factor influencing recovery time. SummaryClinicians should pay attention to several influencing factors for RLN injury before MWA and TEG-D was an independent influencing factor for recovery time of hoarseness after MWA.

Ultrasound guided percutaneous ethanol injection (PEI) for the treatment of cystic and predominantly cystic thyroid nodules: a single centre experience

Ultrasound guided percutaneous ethanol injection (PEI) for the treatment of cystic and predominantly cystic thyroid nodules: a single centre experience

STU3Net: An Improved U‐Net With Swin Transformer Fusion for Thyroid Nodule Segmentation

ABSTRACTThyroid nodules are a common endocrine system disorder for which accurate ultrasound image segmentation is important for evaluation and diagnosis, as well as a critical step in computer‐aided diagnostic systems. However, the accuracy and consistency of segmentation remains a challenging task due to the presence of scattering noise, low contrast and resolution in ultrasound images. Therefore, we propose a deep learning‐based CAD (computer‐aided diagnosis) method, STU3Net in this paper, aiming at automatic segmentation of thyroid nodules. The method employs a modified Swin Transformer combined with a CNN encoder, which is capable of extracting morphological features and edge details of thyroid nodules in ultrasound images. In decoding through the features for image reconstruction, we introduce a modified three‐layer U‐Net network with cross‐layer connectivity to further enhance image reduction. This cross‐layer connectivity enhances the network's capture and representation of the contained image feature information by creating skip connections between different layers and merging the detailed information of the shallow network with the abstract information of the deeper network. Through comparison experiments with current mainstream deep learning methods on the TN3K and BUSI datasets, we validate the superiority of the STU3Net method in thyroid nodule segmentation performance. The experimental results show that STU3Net outperforms most of the mainstream models on the TN3K dataset, with Dice and IoU reaching 0.8368 and 0.7416, respectively, which are significantly better than other methods. The method demonstrates excellent performance on these datasets and provides radiologists with an effective auxiliary tool to accurately detect thyroid nodules in ultrasound images.

Next generation sequence-based targeted somatic mutation analysis in thyroid nodules with pathologically diagnosed as indeterminate cytology

PurposeThe management of indeterminate thyroid nodules remains a topic of ongoing debate, particularly regarding the differentiation of malignancy. Somatic mutation analysis offers crucial insights into tumor characteristics. This study aimed to assist the clinical management of indeterminate nodules with somatic mutation analysis. Methods: Aspiration samples from 20 indeterminate thyroid nodules were included in the study. A next-generation sequencing panel containing 67 genes was used for molecular profiling. The results were compared with pathology data from surgical material, which is considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results: Variants in six genes (NRAS, BRAF, TP53, TERT, PTEN, PIK3CA) were detected in 10 out of 20 samples. We identified nine Tier 1 or 2 variants in 10 (67 %) out of 15 malignant nodules (NRAS, BRAF, TP53, TERT, PTEN, PIK3CA) and one Tier 2 (PIK3CA) variant in one out of five benign nodules. The study demonstrated an NPV of 40 %, a PPV of 90 %, a specificity of 80 %, and a sensitivity of 60 %. Conclusion: Based on the detected molecular markers, at least nine patients (45 %) could be managed correctly without needing a repeat FNAB attempt. This study underscores the clinical practicality of molecular tests in managing nodules with indeterminate cytology. Additionally, this study emphasizes the importance of considering the patient's age when determining the DNA- or RNA-based genetic testing method. Finally, we discussed the significance of the somatic mutation profile and its impact on the current pathological classification.

Research on the expression of Mir-218-2 in the serum of patients with papillary thyroid cancer and its clinical significance.

Papillary thyroid carcinoma is an epithelial malignancy with follicular cell differentiation and sets of defined nuclear features and appearance of an irregular solid mass. The main objective of our study is to research on the expression of miR-218-2 in the serum of patients with papillary thyroid cancer and its clinical significance. Our study involved patients with thyroid nodules were divided into a capitate cancer group (N = 100) and a benign nodule group (N =100). Lastly, 50 cases of healthy individuals were used as controls. The total sample size was 250. All cases were clinically diagnosed and underwent histopathological examinations at the Tonglu County Hospital of Traditional Chinese Medicine between January 2023 and January 2024. Quantitative RT-PCR was used to assess the expression levels of miR-218-2 and its host gene SLIT3 in normal and cancer thyroid tissues. We found that 45% of tumour sizes were less than 1 cm with 90% of tumours did not infiltrate the glandular capsule, implying a favourable prognosis. Lastly, 85% of tumours were well differentiated with about 75% showing no metastasis while 60% of TNM stage were classified as stage I. Also, miR-218-2 and its host gene SLIT3 are significantly down-regulated in papillary thyroid carcinoma. The inhibitory effects of miR-218-2 act in synergy with its host gene SLIT3 to alter the rates of cell invasion, cell migration and cell proliferation. Our findings have clinical significance on the involvement of miR-218-2 and SLIT3. There exists a functional relationship between host genes and intronic miRNAs in the tumorigenesis of thyroid cancers.

Thyroid Dysfunction Secondary to Endocrine Disruptive Chemicals – A Systematic Review

Objectives: To assess the epidemiological data and potential connection between different endocrine chemical disruptors and thyroid hormone abnormalities. Study Design: The 2020 PRISMA standards were followed when conducting the systematic review. Ten research studies were found and examined after an in-depth review of the scientific literature. Methodology: The systematic review was aimed to gather all pertinent information, including observational studies (prospective or retrospective cohorts) that address the relationship between exposure to endocrine disruptors and thyroid hormone imbalance. Results: Ten studies were found, and they demonstrated that these substances, especially in adulthood, impact the level of thyroid hormone and the incidence of thyroid nodules. Conclusions: Endocrine disruptive chemicals can compromise thyroid function by affecting hormone transporters, gene expression, and the hypothalamic-pituitary-thyroid axis.

Serum trace elements show association with thyroperoxidase autoantibodies in Thyroid Imaging Reporting and Data System (TI-RADS) 4 nodules

Thyroid nodule (TN) has been becoming a great concern worldwide due to its high incidence. Although some studies have reported associations between trace elements exposure and the risk of TNs, the linkage was not inconclusive. The present study aimed to identify the association of selected serum trace elements (Ca, Mg, V, Fe, Co, Cu, Zn, Se, Mn and Mo) with TNs among general adults. A cross-sectional study was conducted in January 2021 in Chengdu, China. 1282 subjects completed the questionnaire and gave at least one human biological material after an overnight fast, venous blood, and urine, including 377 TN participants defined through ultrasound. Various trace elements in serum specimens were determined by inductively coupled plasma mass spectrometry. Thyroid functions were tested by chemiluminescent microparticle immunoassay (CMIA). The associations between trace elements levels and the risk of TNs were examined by restricted cubic splines (RCS) regression and bayesian kernel machine regression (BKMR) models. TNs were more common in females (P < 0.001) and in the elderly (P < 0.001) and that they were also frequently associated with fertility, marital status, annual household income, drinking, anxiety, vitamin supplement, tea consumption, hypertension and hyperlipidemia. After adjusting for confounders by a propensity score matching model, the association between trace elements concentrations and TNs risk was found to be statistically insignificant in the RCS (P for nonlinear > 0.05) and BKMR models. FT3 or T4 (total or free) increased significantly with increasing total trace elements mixture levels. In TI-RADS-4 TN subjects, TPO-Ab level increased significantly with increasing total trace elements mixture levels in the high-dose range. Ca, Zn, Mo at their 75th percentile showed positive individual effects on TPO-Ab, which was examined to be interactive. The detection of trace elements for TNs in general adults may be of no significance, but once individuals classified as TI-RADS-4 TNs are detected with abnormal TPO-Ab, Ca, Zn and Mo level are recommended to measure. The substantive association on it still needs to be continuously explored in the future.

Serum thyroid autoantibodies in malignant thyroid nodules

Background: Thyroid cancer is one of the most common malignant tumours of the endocrine system. Thyroid autoantibodies were reported to be associated with malignant thyroid nodules. This study aimed to assess the diagnostic accuracy of serum thyroid autoantibody levels for malignant thyroid nodules. Methods: From March 2023 to January 2024, we recruited 104 consecutive patients with thyroid nodules confirmed by ultrasonography in three departments of Bangabandhu Sheikh Mujib Medical University. Out of these, 52 were diagnosed with malignant thyroid nodules using fine needle aspiration cytology, while the remaining 52 had benign thyroid nodules. Serum thyroid autoantibodies were measured using the immunoassay technique. Results: The mean levels of serum thyroid peroxidase antibody (TPOAb) were significantly higher (P&lt;0.001) in the malignant group compared to the benign group (36.1 versus 24.0 IU/mL). The mean levels of serum thyroglobulin antibodies (TgAb) were also significantly higher (P&lt;0.001) in the malignant group (39.8 IU/mL versus 29.1 IU/mL). Elevated TPOAb (&gt;40 IU/mL) and TgAb (&gt;35 IU/mL) showed reasonable accuracy (60% to 65%) in detecting malignancy of thyroid nodules. Conclusions: Thyroid malignancy is positively associated with TgAb and TPOAb. Therefore, thyroid autoantibodies could be considered for screening malignancy in thyroid nodules.

Enhancing diagnostic precision in thyroid nodule assessment: evaluating the efficacy of a novel cell preservation technique in fine-needle aspiration cytology.

This study aimed to evaluate the effectiveness of thyroid fine needle aspiration cytology (FNAC) using a novel-cell preserving matrix called Cytomatrix in improving diagnostic accuracy for thyroid nodules. Fifty patients undergoing thyroidectomy were enrolled and FNAC was performed on the excised thyroid glands, with the collected sample being placed on the Cytomatrix. The results were compared with histopathological analysis, and diagnostic performance was assessed statistically. Cytomatrix demonstrated an accuracy of 96%, sensitivity of 84.61%, and specificity of 100%. Concordance between cytological and histopathological findings highlighted Cytomatrix's potential to enhance thyroid FNAC accuracy. FNAC using Cytomatrix shows promise in improving diagnostic accuracy for thyroid nodules. Its application, marked by faster processing and efficient resource utilization, coupled with the preservation of cellular architecture, holds considerable potential in enhancing cytological diagnosis, thus optimizing patient management strategies.

Approach to the Patient: Challenging Cases of Pediatric Thyrotoxicosis.

Graves' disease (GD) is the leading cause of hyperthyroidism in children. However, compared to adults GD in children is a rare condition. In a recent guideline issued by the European Thyroid Association the diagnostic evaluation and treatment of pediatric GD is described extensively. In this article we go beyond the guideline and describe the potential challenges of establishing the right etiology of thyrotoxicosis in children, illustrated by cases of thyroid hormone resistance, autonomous functioning thyroid nodules and subacute thyroiditis with a thyrotoxic phase. In addition, we report therapeutic challenges in pediatric GD such as recurrent immunological flare-ups under anti-thyroid drug (ATD) treatment, innovative ways to improve ATD compliance and the role of definitive treatment in persistent complaints of malaise under ATD treatment.

Management of Indeterminate Thyroid Nodules: A Model Comparing Surgery, Molecular Testing, and Observation.

Optimal management of indeterminate nodules remains a controversial area of endocrine surgery. The purpose of this study is to compare observation, molecular testing, and immediate thyroid surgery for the management of Bethesda Classes III and IV nodules in patients age 50 to 90 years. A decision analysis was performed from April 22, 2021, to September 29, 2023, using a Markov model constructed with TreeAgePro 2023. Model variables and ranges were selected based on literature review data. TreeAgePro. A 1-way sensitivity analysis was performed to evaluate the age threshold at which each management pathway, immediate thyroid surgery, additional molecular testing, or observation, would be favored. A Monte Carlo probabilistic sensitivity analysis was performed 5 times with model patients assigned starting ages of 50, 60, 70, 80, and 90 years to assess how age at diagnosis would impact model results. Outcomes were measured with quality-adjusted life-years and accounted for perioperative complications including permanent recurrent laryngeal nerve injury, permanent hypoparathyroidism, and medical complications. In the study models, molecular testing was more beneficial than surgery and observation across all ages. The age threshold at which observation became more beneficial than surgery as the next best option was 83.1 years. However, the clinical difference between all 3 treatment algorithms was relatively minimal. Decision-making regarding indeterminate thyroid nodules is complex. Given the clinically similar results across all 3 treatment algorithm, this study reinforces that treatment modalities should be individually tailored and based on shared physician-patient decision making.