Thyroid Nodules Research Articles

EIF1AX mutation in thyroid nodules: a histopathologic analysis of 56 cases in the context of institutional practices.

EIF1AX mutation has been identified as a driver mutation for papillary thyroid carcinoma (PTC) by The Cancer Genome Atlas (TCGA) study. Subsequent studies confirmed this mutation in PTC and Anaplastic Thyroid Carcinoma (ATC) but also reported EIF1AX mutation in Follicular nodular disease (FND) and benign thyroid nodules. In this study, we review thyroid nodules with EIF1AX mutation from two institutions: a tertiary care hospital (YNHH, n = 22) and a major cancer referral center (MSKCC, n = 34) and report the varying histomorphology in the context of additional genetic abnormalities and institutional practices. Pathology diagnoses were reviewed according to the WHO 5th edition and correlated with the type of EIF1AX mutation and additional concurrent molecular alterations, if any. Most cases were splice site type mutations. Cases consisted of 9 FND, 7 follicular (FA) or oncocytic adenomas (OA), 2 non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) and 38 follicular-cell derived thyroid carcinomas. Of 8 cases with isolated EIF1AX mutation, 7 were FND, FA or OA (88%) and one was an oncocytic carcinoma (12%). Of 12 cases with EIF1AX and one additional molecular alteration, 9 (75%) were FND, FA or OA, 2 (17%) were NIFTPs and one (8%) was a poorly differentiated thyroid carcinoma. All 36 cases with EIF1AX mutation and molecular alterations were malignant (100%) and included TP53 and TERT promoter mutations associated with ATC (n = 8) and high-grade follicular cell-derived non-anaplastic carcinoma (HGC, n = 2). Isolated EIF1AX mutation was noted only in thyroid nodules seen at YNHH and were predominantly encountered in benign thyroid nodules including FND. Accumulation of additional genetic abnormalities appears to be progressively associated with malignant tumors.

The value of preoperative molecular testing in the management of Bethesda V and Bethesda VI thyroid tumors.

The incidence of thyroid cancer has increased over recent years due to the fact that several diagnostic tools, such as neck ultrasound and fine-needle aspiration, are being ever more widely adopted. Lately, another modality which might provide significant information preoperatively on the aggressiveness of a thyroid tumor, its prognosis, and its recurrence rate is molecular testing. We reviewed the literature with regard to the role of preoperative molecular testing in patients with Bethesda V and Bethesda VI thyroid nodules and its impact on choice of the optimal treatment strategy. Several molecular mutations and alterations are associated with thyroid cancer and its biological behavior, such as BRAF-V600E, RET, and TERT promoter. Although the value of preoperative molecular testing for indeterminate nodules (Bethesda III and Bethesda IV) have been analyzed in numerous studies, the impact of preoperative molecular testing on Bethesda V and Bethesda VI thyroid nodules is not adequately described in the current literature. The preoperative recognition of specific molecular mutations, such as BRAFV600E and TERT promoter mutation, might provide more individualized management for thyroid cancer patients by altering the surgical approach and the extent of surgery for patients diagnosed with a more aggressive or iodine-resistant subtype of thyroid cancer.Thyroid cancer is characterized by multiple genetic mutations and alterations and, as a result, preoperative molecular testing of malignant nodules could be a very useful tool for surgeons, enabling them to decide on the most appropriate surgical approach for each patient.

Thermal Ablation for Benign Thyroid Nodules and Papillary Thyroid Microcarcinoma.

Ultrasound-guided minimally invasive thermoablative (MIT) therapies are a therapeutic option for selected patients with large, hypoenhancing, benign thyroid nodules that cause compression disorders or aesthetic discomfort. MIT, which does not require general anaesthesia, causes thermal necrosis of the treated nodule, which is reduced in size by 50 % without functional consequences, and is indicated for patients who are not too young or in the presence of anaesthesia-related risk factors or recurrence following thyroidectomy or refusal of surgery. For the above indications, MIT complements surgery but does not replace it; it must always be performed in centres and by surgeons with proven technical skills and clinical experience. Subject to appropriate informed consent, the treatment is short-duration, well-tolerated by the patient, safe, and non-invasive. It does not require anaesthesia and complications are rare and transient. MIT, and in particular laser-based procedures (TAL), can also be effective and safe for the treatment of potentially destructible papillary microcarcinoma, as shown by the limited but sufficient literature, including the most recent guidelines, which consider it to be a therapeutic alternative that requires a better understanding of its efficacy and safety.

Diagnostic Performance of Thyroid FNA: Experience of Belarusian National Referral Thyroid Cancer Center.

A fine-needle aspiration (FNA) biopsy is a basic procedure to verify the morphology of thyroid nodules. However, significant variations in the diagnostic performance of FNA, as well as fluctuations in the rate of malignancy (ROM) in different categories of the Bethesda System for Reporting Thyroid Cytopathology, have been discovered in many studies. The development and employment of additional molecular tests in daily clinical practice require an understanding of the prevalence and structure of thyroid malignancy in each category of the Bethesda system. Current research is a continuous retrospective cohort study of the results of the examination and treatment of 1652 patients with thyroid tumors who have undergone primary surgery in 2021 at a national referral thyroid cancer center. FNA diagnostic performance was studied by comparing cytological diagnoses with histological outcomes. The authors evaluated ROM in each Bethesda category and identified the tumors representing a diagnostic pitfall. The overall ROM was 72.4%. When considering ROM in each Bethesda category, it was 16.7% in Bethesda I, 10.1% in Bethesda II, 23.0% in Bethesda IV, 74.8% in Bethesda V, 99.4% in Bethesda VI. The false-positive rate was 65.0%, false negative-0.67%. Follicular and oncocytic adenomas, as well as the follicular variant of papillary thyroid cancer, were the most troublesome entities for patients' management. ROM was comparable to the values implied by the Bethesda system. Follicular tumors were the main source of high false-positive rates. This necessitates the refinement of existing tests and the development of new diagnostic tests to overcome the abovementioned problems.

Clinical, ultrasound and anatomopathological concordance of thyroid nodules in Kinshasa: a cross-sectional study

BackgroundThe European Thyroid Association Thyroid Imaging Data and Reporting Systems (EU-TIRADS) is widely used in the risk stratification of thyroid nodule malignancy. However, data on the subject in Sub-Saharan Africa are limited. The objective of this study is to evaluate the clinical, sonographic and histopathological concordance of thyroid nodules in the diagnosis of thyroid cancer.MethodsThis was an analytical cross-sectional study that examined the clinical, ultrasound and pathological data of 61 patients from 4 hospitals in the city province of Kinshasa over a period of 24 months, from June 01, 2020 to May 31, 2022.ResultsOf the 61 patients, their mean age was 47.38 ± 8.8 years. The mean clinical score of the patients was 3.4 ± 0.84 with the extremes ranging from 1 to 5. The majority of the patients were classified as having an intermediate risk, ie 85.2% of the cases. It was noted that 41% of the nodules had a high risk according to the EU-TIRADS score and 8.2% of the nodules were malignant after histopathological analysis. The ROC curves reported at the diagnosis of malignancy show an area under the curve of 0.709 with 95% CI (0.486–0.931), a Youden index of 0.769 for the clinical score, and an area under the curve of 0.830 with 95% CI (0.605–0.995), a Youden index of 0.772 for the EU-TIRADS score.ConclusionIn a low-income country, a well-performed thyroid ultrasound and the well-applied clinical score could be an important tool in the selection of thyroid nodules suspected of malignancy and requiring histopathological examination to avoid excessive acts in the patient.

Assessing the Diagnostic Accuracy of TI-RADS in Pediatric Thyroid Nodules: A Multi-Institutional Review

PurposeThyroid nodules are uncommon in children and adolescents but carry an increased risk of malignancy when present. The Thyroid Imaging Reporting and Data System (TI-RADS) is an adult-validated ultrasound-based risk assessment providing a prediction of malignant potential for thyroid nodules, thereby guiding recommendations for fine needle aspiration biopsy (FNAB). Minimal data exist regarding the applicability of TI-RADS to predict malignancy in pediatric thyroid nodules. This study aims to analyze the performance of TI-RADS for children and adolescents with thyroid nodules, hypothesizing that applying TI-RADS criteria would improve accuracy and reduce the number of recommended FNAB compared to American Thyroid Association (ATA) size criteria alone. MethodsA multi-institutional retrospective analysis was conducted including patients < 21 years with a thyroid nodule by sonographic thyroid imaging between 2015-2020. TI-RADS scores were assigned at each institution by a pediatric radiologist trained in thyroid imaging and TI-RADS criteria. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy of TI-RADS scoring were compared to existing ATA size-based recommendation for performing a FNAB. Accounting for relative size differences between adults and children, a novel PED TI-RADS category was developed and tested, recommending FNAB for thyroid nodules with a TI-RADS 3 and >1.5cm, TI-RADS 4 and >1.0cm, and TI-RADS 5 any feasible size. Results291 nodules from 260 patients (median age 14.9 years, 78.8% female) were assessed using TI-RADS. Applying adult TI-RADS criteria resulted in recommendation of FNAB for 35.1% of nodules, in contrast to 76.6% recommended by ATA guidelines (p<.0001) (Table). Utilizing the adult TI-RADS score ≥ 3 as an FNAB indicator resulted in 100% sensitivity and 28.5% specificity, with 0 cases of missed malignant nodules on pathology. When novel PED TI-RADS criteria were applied, 88 patients would have been spared an unnecessary FNAB with improved sensitivity and accuracy over ATA criteria. ConclusionsThe application of adult and PED TI-RADS scoring to thyroid nodules in pediatric patients enhances the accuracy of malignancy prediction compared to current American Thyroid Association size criteria alone. The utilization of PED TI-RADS scoring eliminated unnecessary biopsies in many children while not missing a single thyroid malignancy. Level of EvidenceLevel III

Prevalence of malignancy in thyroid nodules with AUS cytopathology: A retrospective cross-sectional study.

Category III (AUS; Atypia of Undetermined Significance) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was established to describe thyroid nodule features that are neither benign nor cancerous. This study aims to evaluate the rate of thyroid malignancy in patients diagnosed with AUS at the Armed Forces Hospital Southern Region (AFHSR), Saudi Arabia. The patients (508) diagnosed with AUS in their thyroid nodules underwent fine-needle aspiration cytology (FNAC). Data were collected through a chart-based approach, reviewing patients' medical records and relevant information. Among the cases, the majority were females (84.6%). Among the different age groups, individuals between 40 and 50 years had the highest prevalence of thyroid nodules (32.5%). Approximately 27% of patients exhibited tumor sizes larger than 4 cm. FNAC results revealed 16.5% benign, 26% AUS, and 22.4% follicular neoplasm cases. Histopathology indicated 54.1% of benign and 37.2% of malignant cases. Papillary carcinoma accounts for 80.4% of all malignant cases. A significant correlation was observed between FNAC and postoperative histopathology (P value < 0.05). Hypoechoic nodules exhibited 33.9% of malignant cases, and calcification was observed in 25% of the cases. A significant association was found between malignancy and echogenicity and between malignancy and calcification (P value = 0.003 and 0.001, respectively). The findings of this study identify malignancy in thyroid nodules with AUS cytopathology, particularly in the Southern region of Saudi Arabia. The correlation between pre-surgery FNAC and postoperative histopathology supports FNAC's diagnostic value. Additionally, echogenicity and calcification can potentially contribute to predicting nodule malignancy.

Enhanced Early Detection of Thyroid Abnormalities using a Hybrid Deep Learning Model: A Sequential CNN and K-Means Clustering Approach

The thyroid gland, often referred to as the butterfly gland due to its shape, is located in the neck and plays a crucial role in regulating metabolism. It is susceptible to various health conditions, including hypothyroidism, hyperthyroidism, thyroid cancer, and thyroid nodules. Early detection of these conditions is essential for accurate diagnosis and effective treatment. Detecting thyroid nodules using machine learning and deep learning techniques presents a challenging yet promising research avenue. The choice of model depends on the characteristics of the patient's thyroid data, the dataset size, and the available computational resources. Hybrid models can be employed to handle complex data more effectively. In this study, a sequential Convolutional Neural Network (CNN) model was developed due to its capability to automate feature extraction and focus on Regions-of-Interest (ROIs) for detecting thyroid abnormalities. The proposed model achieved an accuracy of 81.5%, with a precision of 97.4% and a sensitivity of 83.1%, indicating its robustness in classifying images as benign or malignant. The confusion matrix provided further performance insights. Data segmentation was enhanced using K-means clustering for its scalability and efficiency in processing large medical image datasets. Compared to traditional models, the proposed hybrid approach demonstrated a significant improvement in diagnostic accuracy and precision, achieving performance gains of approximately 15-20% over baseline methods. These advancements underscore the potential of integrating machine learning and deep learning in medical diagnostics, paving the way for more reliable and efficient diagnostic tools for healthcare professionals.

Thyroid Nodules with Atypia of Unknown Significance (TBSRTC III): Evaluating the Role of Repeat FNA, Molecular Testing, and Surgery Across Five Hospitals

Thyroid Nodules with Atypia of Unknown Significance (TBSRTC III): Evaluating the Role of Repeat FNA, Molecular Testing, and Surgery Across Five Hospitals

Les cancers thyroïdiens : diagnostic et suivi

AbstractThyroid cancers are often diagnosed during the exploration of a thyroid nodule. They are developed at the expense of follicular cells mainly differentiated of papillary or vesicular types and associated with a good prognosis, more rarely of oncocytic type and exceptionally of anaplastic type, associated with a poor prognosis. Medullary thyroid carcinomas are developed at the expense of C cells and are part of a MEN 2, associated with a proto-oncogene RET mutation in 25% of cases. Thyroid function is generally conserved. Diagnosis is based on ultrasound, which will characterize the thyroid nodule(s) and the cervical adenopathies to be punctured. The cyto-histological examination establishes the definitive diagnosis and the classification of the tumor determining the management and follow-up. A total or partial thyroidectomy is performed, possibly associated with lymph node removal. Hypothyroidism is quasi-systematic after surgery requiring a supplementation by L-thyroxine. In thyroid differentiated carcinomas, a high L-thyroxine dosage to suppress TSH and an adjuvant iratherapy (1131) are recommended in the forms with high risk of recurrence. Biological follow-up relies on serum thyroglobulin, indetectable in the absence of relapse. In the case of medullary carcinoma, biological follow-up relies on serum calcitonin, indetectable in the absence of persistence or recurrence and carcinoembryonic antigen (CEA). The search for a RET mutation is always recommended.

Nuclear Imaging Modalities in the Diagnosis and Management of Thyroid Cancer.

In this review we have brought forward various nuclear imaging modalities used in the diagnosis, staging, and management of thyroid cancer. Thyroid cancer is the most common endocrine malignancy, accounting for approximately 3% of all new cancer diagnoses. Nuclear imaging plays an important role in the evaluation of thyroid cancer, and the use of radioiodine imaging, FDG imaging, and somatostatin receptor imaging are all valuable tools in the management of this disease. Radioiodine imaging involves the use of Iodine-123 [I-123] or Iodine-131 [I-131] to evaluate thyroid function and detect thyroid cancer. I-123 is a gamma-emitting isotope that is used in thyroid imaging to evaluate thyroid function and detect thyroid nodules. I-131 is a beta-emitting isotope that is used for the treatment of thyroid cancer. Radioiodine imaging is used to detect the presence of thyroid nodules and evaluate thyroid function. FDG imaging is a PET imaging modality that is used to evaluate the metabolic activity of thyroid cancer cells. FDG is a glucose analogue that is taken up by cells that are metabolically active, such as cancer cells. FDG PET/CT can detect primary thyroid cancer and metastatic disease, including lymph nodes and distant metastases. FDG PET/CT is also used to monitor treatment response and detect the recurrence of thyroid cancer. Somatostatin receptor imaging involves the use of radiolabeled somatostatin analogues to detect neuroendocrine tumors, including thyroid cancer. Radiolabeled somatostatin analogues, such as Indium-111 octreotide or Gallium-68 DOTATATE, are administered to the patient, and a gamma camera is used to detect areas of uptake. Somatostatin receptor imaging is highly sensitive and specific for the detection of metastatic thyroid cancer. A comprehensive search of relevant literature was done using online databases of PubMed, Embase, and Cochrane Library using the keywords "thyroid cancer," "nuclear imaging," "radioiodine imaging," "FDG PET/CT," and "somatostatin receptor imaging" to identify relevant studies to be included in this review. Nuclear imaging plays an important role in the diagnosis, staging, and management of thyroid cancer. The use of radioiodine imaging, thyroglobulin imaging, FDG imaging, and somatostatin receptor imaging are all valuable tools in the evaluation of thyroid cancer. With further research and development, nuclear imaging techniques have the potential to improve the diagnosis and management of thyroid cancer and other endocrine malignancies.

Detection of RAS p.Q61R by Immunohistochemistry in Practice: A Clinicopathologic Study of 217 Thyroid Nodules with Molecular Correlates.

RAS p.Q61R is the most prevalent hot-spot mutation in RAS and RAS-like mutated thyroid nodules. A few studies evaluated RAS p.Q61R by immunohistochemistry (RASQ61R-IHC). We performed a retrospective study of an institutional cohort of 150 patients with 217 thyroid lesions tested for RASQ61R-IHC, including clinical, cytologic and molecular data. RASQ61R-IHC was performed on 217 nodules (18% positive, 80% negative, and 2% equivocal). RAS p.Q61R was identified in 76% (n = 42), followed by RAS p.Q61K (15%; n = 8), and RAS p.G13R (5%; n = 3). NRAS p.Q61R isoform was the most common (44%; n = 15), followed by NRAS p.Q61K (17%; n = 6), KRAS p.Q61R (12%; n = 4), HRAS p.Q61R (12%; n = 4), HRAS p.Q61K (6%; n = 2), HRAS p.G13R (6%; n = 2), and NRAS p.G13R (3%; n = 1). RASQ61R-IHC was positive in 47% of noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP; 17/36), 22% of follicular thyroid carcinomas (FTC; 5/23), 10% of follicular thyroid adenomas (FTA; 4/40), and 8% of papillary thyroid carcinomas (PTC; 9/112). Of PTC studied (n = 112), invasive encapsulated follicular variant (IEFVPTC; n = 16) was the only subtype with positive RASQ61R-IHC (56%; 9/16). Overall, 31% of RAS-mutated nodules were carcinomas (17/54); and of the carcinomas, 94% (16/17) were low-risk per American Thyroid Associated (ATA) criteria, with only a single case (6%; 1/17) considered ATA high-risk. No RAS-mutated tumors recurred, and none showed local or distant metastasis (with a follow-up of 0-10 months). We found that most RAS-mutated tumors are low-grade neoplasms. RASQ61R-IHC is a quick, cost-effective, and reliable way to detect RAS p.Q61R in follicular-patterned thyroid neoplasia and, when malignant, guide surveillance.

Application of Afirma Gene Sequencing Classifier in assessment of Cytologically Indeterminate Thyroid Nodules: A Middle Eastern Population Study

Application of Afirma Gene Sequencing Classifier in assessment of Cytologically Indeterminate Thyroid Nodules: A Middle Eastern Population Study

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.