We have studied 144 patients with anaplastic thyroid carcinoma (ATC) to evaluate the utility of a select panel of immunohistochemical stains for diagnosis and to better define their spectrum of histologic features. There were 97 women and 47 men, aged 48 to 103 years (mean: 67.8). The tumors were seen against a background of papillary thyroid carcinoma in 33 cases, follicular thyroid carcinoma in 28, poorly differentiated carcinoma in 5, and thyroid nodular disease in 31. Histologically, two basic patterns of growth were observed, one predominantly composed of spindle and pleomorphic cells, and one composed of round epithelioid cells. Several unusual morphologic features were also observed focally that can introduce difficulties for diagnosis, including tumors with squamous differentiation (47 cases; 32.6%), clear cells (17; 11.8%), paucicellular (17; 11.8%), inflammatory (16; 11%), pseudoangiosarcomatous (11; 7.6%), rhabdoid (9; 6.2%), and osteoclastic giant cells (8; 5.5%). Immunohistochemical staining was performed in 107 cases: AE1/AE3 cytokeratin stains were positive in 63 cases (58.8%) and CK8/18 in 46 (37.3%); PAX8 was positive in 35 cases (32.7%); TTF1 was only focally positive in 4 cases (3.7%); p40 was positive in 22 cases (20.5%), mostly in the areas of squamous differentiation. Strong CD10 positivity was also seen in 97 cases (90.6%). Our study shows that anaplastic carcinoma has the potential for simulating a large variety of tumors and underscores the difficulties for making the diagnosis using immunohistochemistry; cytokeratins, PAX8 and TTF1 were of limited utility and showed inconsistent results emphasizing the importance of clinicopathologic correlation for the diagnosis.

Redefining Thyroid Nodule Evaluation: Demographics, Misleading Symptoms, and Diagnostic Challenges. Insights From a Multicenter Study.

Background: Thyroid disorders represent some of the most common endocrine conditions worldwide, and considerable proportions require surgical intervention. Their burden remains particularly relevant in countries with a history of or ongoing iodine deficiency, where nodular thyroid disease continues to be widespread. Objective: This study aimed to describe the epidemiological and clinical characteristics of patients undergoing thyroid surgery at a tertiary referral center in Albania. Methods: A retrospective descriptive study was conducted, including 211 patients managed at the “Mother Teresa” University Hospital Center in Tirana. Data were analyzed regarding age, sex, residence, symptoms, family history, clinical presentation, preoperative diagnosis, and hospital stay. Results: Among 211 patients, 88.1% were female, with a mean age of 46.4 years. The most frequent diagnosis was nodular goiter. Neck swelling was the main complaint in over 60% of cases. Total thyroidectomy was performed in 86% of patients. Thirty percent had a family history of thyroid disease. Most patients lived in urban areas, mainly Tirana. Conclusions: Nodular thyroid disease remains highly prevalent with a marked female predominance. Neck swelling is the most frequent presenting symptom. Despite preventive strategies, iodine deficiency continues to play a role as a contributing factor. Early diagnosis, appropriate surgical management, and structured follow-up are essential to improve outcomes.

BACKGROUND Insulin autoimmune syndrome (IAS) is a rare cause of spontaneous hyperinsulinemic hypoglycemia, characterized by high titers of insulin autoantibodies in the absence of prior insulin exposure. It is most frequently reported in Asian populations and is often associated with other autoimmune conditions. Reports in White patients remain uncommon. CASE REPORT We describe a 63-year-old White woman presenting with recurrent symptomatic hypoglycemia, with plasma glucose as low as 27 mg/dL. Episodes were accompanied by sweating and transient loss of consciousness. Several weeks before the first episode of hypoglycemia, she experienced a single episode of a pruritic rash, which resolved spontaneously. The patient had no prior exposure to insulin therapy or sulfhydryl-containing drugs. Laboratory evaluation revealed markedly elevated insulin concentrations (reaching 19 300 μU/mL), increased C-peptide levels, and insulin autoantibody titer of 99.9%. Abdominal MRI excluded insulinoma. Continuous flash glucose monitoring demonstrated frequent nocturnal and postprandial hypoglycemic episodes. Additional testing confirmed Hashimoto's thyroiditis and a benign thyroid nodule. Management included dietary modification with frequent small meals and carbohydrate restriction. Because these measures were insufficient, prednisolone was initiated, resulting in rapid improvement in glycemic stability. Corticosteroid dose was tapered over 4 months, and the patient remained euglycemic. CONCLUSIONS IAS should be considered in patients with unexplained hyperinsulinemic hypoglycemia to avoid unnecessary invasive evaluation for insulinoma. When dietary measures alone are inadequate, prednisolone therapy is effective. Given the frequent coexistence of IAS with other autoimmune disorders, systematic screening is advisable, and incidental thyroid findings in the setting of autoimmune thyroiditis warrant careful assessment to exclude malignancy.

Background/Objectives: Thyroid nodules exhibit substantial histopathological variability, and systemic markers that differentiate benign from malignant patterns remain poorly defined. This study evaluated clinical, biochemical, hormonal, and histopathological characteristics in patients undergoing total thyroidectomy for nodular thyroid disease. Methods: A retrospective cohort of 926 patients operated between 2017 and 2024 was analyzed. Patients were classified as: Group 1-benign lesions; Group 2-benign-malignant associations; Group 3-multiple malignant lesions. Demographic, biochemical, hormonal, and histopathological data were assessed using the Kruskal-Wallis and Mantel-Haenszel chi-square tests. Thyroid-specific tumor and autoimmunity markers (calcitonin, thyroglobulin, anti-thyroglobulin antibodies, and thyroid peroxidase antibodies) were not included in the comparative analyses due to their non-uniform availability across the retrospective cohort. Results: Most clinical and biochemical parameters showed no significant differences among the three groups, including TSH (p = 0.122), FT3 (p = 0.560), glycemia (p = 0.829), creatinine (p = 0.193), fibrinogen (p = 0.535), and thyroid dimensions (length p = 0.401, width p = 0.183, thickness p = 0.667, and total thyroid mass p = 0.109). Neutrophil count differed in the overall comparison (p = 0.021), although absolute differences were small, and lymphocyte counts were modestly lower in patients with multiple malignant lesions compared with benign disease (p = 0.009). Comorbidities and BMI were similarly distributed across groups (all p > 0.05). Overall, routinely available clinical, biochemical, and hormonal parameters demonstrated limited discriminatory value between patients with different histopathological patterns. Conclusions: Standard clinical, biochemical, and hormonal markers showed minimal ability to reflect underlying histopathological patterns in patients with thyroid nodules, underscoring their limited utility for preoperative risk stratification.

This study aims to evaluate the predictive performance of preoperative blood lipid profiles combined with thyroid ultrasound features for postoperative nausea and vomiting (PONV) after thyroid lobectomy, and to develop a nomogram for individualized risk assessment. This retrospective study included 269 patients who underwent thyroid lobectomy for nodular thyroid disease at the People's Hospital of Pingyang between January 2022 and December 2024. Study participants were divided into non-PONV (n = 102) and PONV (n = 167) groups. Preoperative clinical details, thyroid ultrasound parameters, and lipid profiles were compared between the two groups. Statistically significant variables (p < 0.05) from the univariate analysis were included in the multivariate logistic regression to identify independent risk predictors. A nomogram was constructed and internally validated using bootstrap resamples (1000 iterations). Multivariate analysis identified Apfel score, thyroid volume, maximum nodule diameter, presence of diffuse changes, total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) as independent risk predictors of PONV. The nomogram showed favorable discriminative performance with an area under the receiver operating characteristic curve of 0.804 (95% CI: 0.749-0.859) and a bias-corrected area under the curve (AUC) of 0.794 (95% CI: 0.737-0.850) after bootstrap validation. Additionally, the model demonstrated favorable calibration and superior clinical utility, as assessed using the decision curve analysis. Multivariate analysis identified that preoperative blood lipid profiles and thyroid ultrasound features are independently associated with PONV. Incorporating these indicators along with established clinical risk factors into a nomogram enables accurate individualized prediction and may support targeted prophylactic interventions.

Evaluating the link between metabolic syndrome components and benign nodular thyroid disease

&amp;lt;p&amp;gt;The aim of this review article is to provide an overview of available literature data on serum basal calcitonin (bCT) and stimulated calcitonin (sCT) cut-off values, highlighting them as a valuable diagnostic tool in everyday thyroidology practice. During the diagnostic evaluation of thyroid nodular disease, mildly elevated bCT values ​​are frequently encountered. If bCT values ​​remain above the reference range but are &amp;amp;amp;lt;100 pg/ml on repeated measurements, further evaluation is warranted. In addition to the usual diagnostic procedure for thyroid nodular disease (medical history, family history of thyroid malignancy, clinical examination, thyroid function tests, and thyroid ultrasonography), a stimulation test, most often a calcium test, is performed to assess the response by measuring the sCT levels. A precise diagnostic threshold, the so-called cut-off for clinically significant pathological values ​​of bCT and sCT that indicate medullary thyroid carcinoma (MTC), is still lacking. However, there are studies that recommend appropriate cut-off values ​​for bCT and sCT that allow a clear and safe distinction between healthy individuals and individuals with C-cell hyperplasia (CCH) from those with MTC. The aim of this review article is to present the latest literature data on existing cut-off values ​​for bCT and sCT in blood, which can certainly be useful to clinicians in everyday practice.&amp;lt;/p&amp;gt;

Background: Headache is a common symptom in acromegaly, but its pathophysiology is complex and often overlooked, leading to diagnostic delays. This can reduce the effectiveness of therapies, which currently have a response rate around 50%. Acromegaly induces systemic inflammation and endothelial dysfunction through elevated GH and IGF-1 levels, contributing to headache development. Timely hormonal therapy might prevent or reduce headache severity. When headache persists, specific preventive treatments should be considered. Methods: A 54-year-old female smoker presented with migraine worsening after menopause and becoming chronic daily in recent months despite well-controlled arterial hypertension. The post-menopausal headache exacerbation was apparently unexplained. She had a history of menstrual migraine since age 35. Additional complaints included insomnia and snoring, with no other significant symptoms. Medical history included bilateral carpal tunnel surgery at age 16, melanoma removal in July 2024, and nodular thyroid disease under endocrinological care. A brain MRI performed to exclude secondary headache revealed a pituitary macroadenoma extending into the cavernous sinus without optic chiasm compression. Visual field testing showed nasal hemifield defects (OS &gt; OD). Endocrinological workup revealed previous galactorrhea and elevated GH and IGF-1 levels. Lanreotide therapy was initiated. Results: After two Lanreotide injections, migraine-like headache completely resolved, with only mild, episodic pressing pain in the left occipitotemporal regions responsive to paracetamol, which also resolved after the next dose. She underwent neurosurgery in April 2025 and currently remains under endocrinological and neurosurgical follow-up. Notably, weight gain and finger enlargement -key signs of acromegaly starting in 2019 - were not initially reported and were only uncovered during a structured follow-up interview. Conclusion: In patients presenting with worsening or chronic migraine, especially when clinical features are atypical or unexplained, secondary causes like acromegaly should be considered. Headache in acromegaly is not solely due to the mechanical effects of the adenoma but it is strongly influenced by the biochemical effects of GH and IGF-1, which promote systemic inflammation and endothelial dysfunction. Early recognition and hormonal therapy can lead to resolution of headache symptoms. Comprehensive history-taking, including probing for subtle signs of acromegaly, and appropriate neuroimaging are essential to reduce diagnostic delays and improve patient outcomes.

The global rise in obesity, metabolic syndrome (MetS), insulin resistance (IR), and type 2 diabetes mellitus (T2DM) is reshaping the epidemiology of thyroid disorders, particularly thyroid nodular disease and differentiated thyroid cancer (DTC). This review summarizes emerging evidence linking metabolic dysfunction to thyroid nodule growth and tumorigenesis. Chronic hyperinsulinemia in IR states activates mitogenic pathways, including PI3K/AKT/mechanistic target of rapamycin (mTOR) and MAPK/ERK. These effects are amplified in thyrocytes overexpressing insulin receptor isoform A (INSR-A) and insulin-like growth factor 1 receptor (IGF1R). Dysfunctional adipose tissue further increases risk through enhanced leptin signaling, reduced adiponectin-mediated AMPK activation, and persistent systemic inflammation and oxidative stress. Environmental factors such as endocrine-disrupting chemicals and gut microbiota alterations add additional susceptibility. Clinical evidence supports these mechanistic links: patients with thyroid nodules consistently show higher HOMA-IR values, and large cohort studies identify MetS as an independent predictor of thyroid nodularity. Female-specific susceptibility appears to be mediated by estrogen receptor activity, adipokine profiles, and postmenopausal fat redistribution. Therapeutically, metformin shows promise via AMPK activation and mTOR inhibition, exerting both metabolic and antiproliferative effects, although randomized trials specific to thyroid cancer outcomes remain limited. Concerns about GLP-1 receptor agonists and thyroid safety are largely theoretical; current data suggest their established cardiometabolic benefits may outweigh potential risks. Converging epidemiological, molecular, and translational evidence underscores the complex interplay between metabolic dysfunction and thyroid diseases. Integrating metabolic health into prevention, risk stratification, and treatment strategies will be essential for advancing precision management of thyroid nodules and DTC.

Disclosure: J. Prim: None. V.Q. Mai: None.Background: Neurofibromatosis Type 1 (NF1) is an inherited neurocutaneous disorder caused by mutations in the neurofibromin gene on chromosome 17. Clinical manifestations of NF1 include the development of neurofibromas, gliomas, and malignant peripheral nerve sheath tumors. We report a rare case of the simultaneous development of ovarian carcinoma and nodular thyroid disease in a patient with NF1.Case Presentation: A 64-year-old woman with a history of NF1 presented for evaluation of thyroid nodules found incidentally on CT imaging. Her medical history was significant for a recent diagnosis of high grade serous ovarian carcinoma for which she had undergone total abdominal hysterectomy, bilateral salpingo--oophorectomy, omentectomy and tumor debulking, and was undergoing chemotherapy with carboplatin and paclitaxel. Previous genetic testing confirmed a pathogenic full gene deletion of NF1 with no other identified mutations known to be associated with gynecologic or thyroid neoplasm risk. Physical exam showed skin freckling, café au lait spots, cutaneous neurofibromas, and palpable left and right-sided thyroid nodules. Thyroid ultrasound confirmed 3 dominant nodules including a 1.3 x 0.8 x 1.1cm solid, hypoechoic LUL nodule; a 2.4 x 2.6 x 2.6cm mixed cystic and solid, isoechoic LLL nodule; and a 3.2 x 2.2 x 3.4cm solid, isoechoic RLL nodule. TSH level was normal. FNA showed nondiagnostic cytology for the LUL thyroid nodule and benign cytology for the LLL and RLL nodules. Discussion: The NF1 gene regulates the Ras oncogene cellular signal transduction pathway with effects on cell growth, division, and survival. There is increasing recognition that the overactive intracellular signaling characteristic of NF1 predisposes to neoplasms of many organs, including an increased risk of benign and malignant neoplasms of the endocrine system. Cases of ovarian serous carcinoma in patients with NF1 are rare, occurring in only 0.5% of patients with NF1 in one large cohort study. However, molecular analysis of tumors identified NF1 mutations in 22% of cases of serous ovarian carcinoma, implicating a role of Ras pathway activation in the pathogenesis of this type of malignancy. Nodular thyroid disease has also been described in NF1, including papillary thyroid cancer. This case study adds to the growing literature identifying cases of neoplastic disease not previously commonly associated with NF1. These findings support the concept that patients with NF1 should be monitored for the development of cancers of endocrine tissues.Presentation: Sunday, July 13, 2025

Disclosure: M.P. Reyes: None. P. Ginier: None. M. Koteles: None.Introduction: Iodine-induced hyperthyroidism (Jod-Basedow phenomenon) occurs when excessive iodine triggers thyrotoxicosis in individuals with nodular thyroid disease. Repeated iodinated contrast exposure can cause severe complications. Identifying high-risk patients and monitoring thyroid function post-contrast exposure is essential. Clinical Case: A 75-year-old male with no prior thyroid disease underwent two iodinated contrast-enhanced CT scans: an abdominal/pelvic CT on 11/29/24 for abdominal pain and vomiting, and a CTA chest on 12/3/24 to rule out pulmonary embolism due to new-onset atrial fibrillation. Combined, these delivered ∼80 g of iodine. The patient was asymptomatic prior to imaging but subsequently developed palpitations, tremor, weight loss, and heat intolerance.On presentation, he had atrial fibrillation with rapid ventricular response. Urinary iodine levels were significantly elevated, with a spot urine iodine of 1512 µg/L on 12/12/24 and 684 µg/L on 12/18/24, reflecting recent high iodine exposure from contrast-enhanced imaging. A follow-up 24-hour urinary iodine test on 12/20/24 showed a level of 972 µg, further confirming ongoing iodine excess. Laboratory tests showed TSH <0.01 µIU/mL, free T4 4.7 ng/dL, and free T3 7.4 ng/dL. Thyroid antibodies were negative. A 2.2 cm left-lobe thyroid nodule was found on ultrasound. Due to recent iodine exposure, radioactive iodine uptake was not performed, as iodine saturation would have rendered the test uninterpretable. RAIU typically becomes reliable four to six weeks post-exposure.A presumptive diagnosis of Jod-Basedow hyperthyroidism was made. Methimazole 40 mg/day and beta-blockade were started, leading to partial improvement. He was readmitted with recurrent atrial fibrillation after missing a beta-blocker dose. Follow-up thyroid function tests showed a shift to hypothyroidism (TSH 10.53 µIU/mL, free T4 0.38 ng/dL), necessitating methimazole discontinuation. Further evaluation of the thyroid nodule via fine-needle aspiration and assessment of abdominal lesions were deferred until stable euthyroidism. Clinical Lessons This case illustrates how high-dose iodinated contrast can unmask thyroid autonomy, causing severe hyperthyroidism. The patient’s course, marked by new-onset atrial fibrillation, readmission, and hypothyroidism, highlights the importance of thorough risk assessment and post-contrast thyroid function monitoring. Baseline thyroid testing and ultrasound should be considered in high-risk individuals. Monitoring with thyroid function tests at two and four weeks post-exposure is crucial for detecting iodine-induced dysfunction. Careful antithyroid medication titration is necessary to avoid overtreatment and iatrogenic hypothyroidism. Recognizing Jod-Basedow hyperthyroidism in high-risk patients is vital to prevent arrhythmias and optimize thyroid management.Presentation: Monday, July 14, 2025

Warburg effect in malign thyroid tissue evidenced using FTIR spectroscopy.

Abstract Most studies on thyroid nodules in Libya have been conducted on histopathological samples. This study was conducted on patients attending endocrine clinics in Benghazi, Libya. This article aims to describe the clinical, radiological, biochemical, and pathological aspects and outcome of nodular thyroid disease in Benghazi, Libya. A total of 227 patients with nodular thyroid disease who attended the endocrine clinics of Benghazi Medical Center and 7th October Hospital during the year 2023 were included in the study. Records were reviewed regarding age, sex, clinical presentation, history of previous head and neck radiotherapy, number and size of nodules, presence and site of lymphadenopathy, thyroid ultrasound features, thyroid-stimulating hormone (TSH), fine-needle aspiration cytology (FNAC) results, outcome (surgery and its type or follow-up), results of histopathology, and final diagnosis. Most of the studied group was females, 213 (93.8%). The mean age ± standard deviation (SD) was 52.3 ± 13.5 years. Multinodular goiter represented the highest percentage and accounted for 142 (62.6%). Mean nodule size ± SD was 2.4 ± 1.5 cm, and the median TSH level was 1.7 mIu/L. Regarding FNAC, most of the cases (110, 44.1%) were benign/colloid goiter, follicular neoplasm, or malignant (19, 8.3%). Among the 54 patients who had a histopathological diagnosis, 26 (48.1%) were proven to have thyroid carcinoma, and most of them had papillary carcinoma (24/26, 92.3%). Among 28 benign cases, 13 (24.5%) had Hashimoto's thyroiditis. Nodular thyroid disease was more common in females; most cases had multiple nodules. FNAC was benign colloid in more than half of the cases, and malignancy or suspicious for malignancy was found in 10% of the cases. Half of the cases with histopathological diagnosis had thyroid carcinoma, and most of them were papillary thyroid carcinoma.

This article examines the clinical effectiveness of modern ultrasound diagnostics and the TI-RADS (Thyroid Imaging Reporting and Data System) classification in assessing malignancy risk in thyroid nodules. Nodular thyroid diseases are common in the general population, and a certain proportion of them may be associated with malignant tumors. Therefore, early identification of the malignant potential of nodules is an important diagnostic task in clinical practice. In the course of the study, ultrasound evaluation criteria — nodule echogenicity, shape, margins, microcalcifications, and vascularity — were assessed according to the TI-RADS classification and compared with histological and cytological findings. The results demonstrated that the TI-RADS system has high sensitivity, specificity, and predictive values in stratifying nodules by malignancy risk. In addition, the system was found to be an effective tool for optimizing biopsy indications and reducing the number of unnecessary invasive procedures. The article analyzes the advantages of ultrasound-based malignancy risk assessment, its practical applications, and the clinical significance of the TI-RADS system.

Background: Thyroid nodules are common in the general population, and most are benign. Thyroidectomy remains the most common treatment for symptomatic benign thyroid nodular disease. The objective of this study is to determine if a novel, cell-specific, nonthermal modality called nanosecond pulsed field ablation (nsPFA) can provide a safe and effective treatment for symptomatic thyroid nodules. Methods: In this clinical feasibility trial (NCT06117085), an nsPFA percutaneous electrode was used to ablate benign thyroid nodules under ultrasound guidance. In Cohort 1 (5 patients), ablations were created during a thyroidectomy procedure (treat-and-resect), so that initial ablation zone characterization could be assessed histologically. In Cohort 2 (20 patients), up to 4 isolated ablations were created in the in situ thyroid for dose-ranging and to allow for estimation of ablation zone volume. In Cohort 3 (5 patients), the entire nodule was ablated with therapeutic intent using multiple, overlapping ablations for resolution of symptoms. Results: For Cohort 1, the mean ablation zone measured 1.7 cm long by 0.7 cm wide post-ablation. For Cohort 2, the mean ablation zone was estimated to be 2.7 cc in volume at 90 days post-ablation (based on nodule size reduction from baseline). Transient dysphonia (<24 hours) was seen in two patients treated at the highest ablation setting (93 mJ/mm2). For Cohort 3, treated nodules had a mean volume reduction of 48.2% as early as 2 weeks, and 71.1% at 1 month and 85.8% at 1 year. Patients could typically resume normal activities on the same day. There was no transient dysphonia in this group. Noticeable volume reduction and relief of symptoms were seen as early as 2 weeks post-treatment. No fibrosis or scars were seen on follow-up ultrasounds. No serious adverse events were reported for any cohorts. Conclusions: This first-in-human study supports the initial safety/efficacy profile of the nsPFA electrode system in treating benign thyroid nodules. The minimally invasive and nonthermal nature of nsPFA energy has the potential to reduce risk of major complications in treatment of benign thyroid nodules as compared with thyroidectomy or thermal ablation and to improve healing through rapid reduction ofablated areas and lack of postprocedural scarring.

Despite their high prevalence and generally benign nature in most cases, the investigation of thyroid nodules still presents potential diagnostic pitfalls, especially in cases with indeterminate cytology results. The performance of molecular markers of thyroid cancer may vary across centers and populations. This study aimed to verify the prevalence of mutations in the BRAF, and RAS genes, and RET/PTC rearrangements in patients undergoing fine-needle aspiration biopsy (FNAB) for thyroid nodule evaluation in a real-world public health service population. Point mutations and rearrangements were detected by Sanger DNA sequencing. A total of 231 thyroid nodules in 220 patients were evaluated, being 86.8% females and a mean age of 55.6 ± 13.9 years. For molecular analysis, high-quality DNA and RNA were obtained from 200 samples. Mutations or rearrangements in target genes were identified in 14% of the 200 samples evaluated. The frequency of the BRAF-like mutations was 5.5%, detected in 9 out of 17 malignant nodules (52.9%) and one in a benign nodule (0.7%). Fourteen RAS-like mutations were identified in benign nodules (57.1% HRAS, 21.5% NRAS and 21.5% KRAS) and only one was present in a malignant nodule (5.9%). Considering only nodules with indeterminate cytology (Bethesda III and IV, n = 53), 9 mutations were detected, 6 in benign histology (all RAS-like), 1 in malignant histology (BRAF-like), and 2 still unoperated, therefore without a histopathological diagnosis. This research concludes that the presence of the BRAF V600E mutation could be useful in supporting the diagnosis of thyroid cancer, due to its high positive predictive value, since 89% of nodules with BRAF V600E mutation were malignant. Additionally, clinical criteria should be established to determine which nodules with RAS-like mutations require closer follow-up, particularly those with indeterminate cytology.

Despite their high prevalence and generally benign nature in most cases, the investigation of thyroid nodules still presents potential diagnostic pitfalls, especially in cases with indeterminate cytology results. The performance of molecular markers of thyroid cancer may vary across centers and populations. This study aimed to verify the prevalence of mutations in the BRAF, and RAS genes, and RET/PTC rearrangements in patients undergoing fine-needle aspiration biopsy (FNAB) for thyroid nodule evaluation in a real-world public health service population. Point mutations and rearrangements were detected by Sanger DNA sequencing. A total of 231 thyroid nodules in 220 patients were evaluated, being 86.8% females and a mean age of 55.6 ± 13.9 years. For molecular analysis, high-quality DNA and RNA were obtained from 200 samples. Mutations or rearrangements in target genes were identified in 14% of the 200 samples evaluated. The frequency of the BRAF-like mutations was 5.5%, detected in 9 out of 17 malignant nodules (52.9%) and one in a benign nodule (0.7%). Fourteen RAS-like mutations were identified in benign nodules (57.1% HRAS, 21.5% NRAS and 21.5% KRAS) and only one was present in a malignant nodule (5.9%). Considering only nodules with indeterminate cytology (Bethesda III and IV, n = 53), 9 mutations were detected, 6 in benign histology (all RAS-like), 1 in malignant histology (BRAF-like), and 2 still unoperated, therefore without a histopathological diagnosis. This research concludes that the presence of the BRAF V600E mutation could be useful in supporting the diagnosis of thyroid cancer, due to its high positive predictive value, since 89% of nodules with BRAF V600E mutation were malignant. Additionally, clinical criteria should be established to determine which nodules with RAS-like mutations require closer follow-up, particularly those with indeterminate cytology.

Achalasia, characterized by impaired esophageal motility, presents a challenge in diagnosis and management. Emerging evidence suggests a potential association between achalasia and thyroid disorders (TD). Understanding the prevalence and treatment response of achalasia in Iranian patients with TD compared to euthyroid counterparts is crucial for optimizing clinical care and informing further research efforts. This study aimed to investigate and compare the response rate to treatment in euthyroid and TD achalasia patients and to determine the prevalence rate of autoimmune TD in individuals with achalasia. This cross-sectional study was conducted on 393 achalasia patients. Initially, the patients underwent thyroid tests to identify any TD. Following these tests, they were treated for achalasia and followed up at 1, 6, and 12 months. The collected data were analyzed to assess the outcomes. The study examined data from 393 patients with achalasia and found no statistically significant correlation between the response rate to treatment in patients with normal thyroid function and those with TD (p = 0.176). Of all the participants, 292 (74.3%) underwent anti-TPO testing, revealing that 60 patients (20.5%) had autoimmune thyroiditis. The analysis showed a notable link between autoimmune thyroiditis and the patients' age (p = 0.024). Achalasia is linked to various TD, including hyperthyroidism, hypothyroidism, and thyroid nodular diseases. Patients with autoimmune TD and esophageal issues should undergo a thorough examination, especially for excessive weight loss. Autoimmune diseases may contribute to inflammation in the esophageal myenteric plexus.

An Updated Review on the Use of Fine Needle Aspiration Biopsy in Pediatric Thyroid Disease.