Thyroid最新文献

Background: Thermal ablation is a minimally invasive treatment for benign thyroid nodules, but its impact on subsequent thyroidectomy and pathological evaluation is uncertain. This study investigates whether preoperative ablation complicates thyroidectomy and poses challenges for pathological diagnosis. Study Design: This retrospective cohort study used prospectively collected institutional registry data on patients with benign thyroid nodules who underwent thyroidectomy after prior radiofrequency ablation. Perioperative outcomes, including thyroidectomy difficulty scale (TDS) and macroscopic adhesion score (MAS), were compared with a control group without prior ablation. Histopathological and cytological changes within the ablated zone and periphery were also evaluated. Results: This study included 165 patients, with 145 in the nonablation group and 20 in the postablation group (17 females, mean age 53.4 years, mean nodule size 4.4 cm, mean interval between ablation and thyroidectomy 29.5 months). Compared with the nonablation group, the ablation group had longer operative time (99.5 vs. 69.5 minutes, p < 0.05), higher TDS (9 vs. 6, p < 0.05), more severe MAS (anterior 50.0% vs. 16.6%, p < 0.05; posterior: 35.0% vs. 16.6%, p < 0.05), and increased incidental parathyroidectomies (10.7% vs. 1.6%, p < 0.05). Histopathologically, the ablated area showed acellular hyalinization (95%), coagulative necrosis (60%), and chronic inflammation (85%). Both central and peripheral regions displayed cytological alterations (nuclear enlargement, focal chromatin clearing, and clear-cell change). Challenges in defining tumor capsule integrity were noted in eight follicular neoplasms, complicating the diagnosis of three follicular carcinomas and two follicular tumors of uncertain malignant potential. Conclusions: Thermal ablation of thyroid nodules may be associated with increased surgical difficulty and adhesion formation during subsequent thyroidectomy. Additionally, ablation-induced tissue alterations can potentially complicate pathological diagnosis. However, due to the small number of study cases, further confirmatory research is needed.

Background: The global incidence of thyroid cancer has increased over the past several decades. While this increase is partially due to increased detection, environmental pollutants have also emerged as a possible contributing factor. Our goal was to perform a systematic review to assess the relationship between environmental air pollution and thyroid cancer. Methods: Systematic literature search was performed using PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases for original articles published prior to March 2024, investigating outdoor air pollution and thyroid cancer/nodules (PROSPERO CRD42024517624). Inclusion criteria included quantitative reporting of pollutant levels and effect size. Specific pollutants included ozone (O₃), particulate matter less than 2.5 (PM_2.5) or 10 microns in diameter (PM₁₀), sulfur dioxide (SO₂), nitric oxides (NO_x), carbon monoxide (CO), and polyaromatic hydrocarbons (PAHs). Study design, sample size, pollution assessment method, covariates, and strength/direction of associations between pollutants and thyroid cancer/nodule detection were extracted, and descriptive synthesis was utilized to summarize pertinent findings. Risk of bias was assessed using the National Heart, Lung, and Blood Institute quality assessment tool. Results: Of 1294 identified studies, 11 met inclusion criteria. Over 6 million patients from diverse regions were represented across studies. Pollutants studied included O₃ in 5 studies; PM_2.5, PM₁₀, SO₂, and NO_x in 3 studies; unspecified PM and CO in 2 studies; and PAHs in 1 study. Primary outcome was thyroid cancer diagnosis among 9 studies and thyroid nodule detection in 2. All studies examining NO_x and O₃ reported increased risks ranging from 1.03 to 1.5-fold and 1.1 to 1.3-fold, respectively. Both studies assessing PM_2.5 reported 1.18 to 1.23-fold increased odds of thyroid cancer diagnosis, and the magnitude of association increased with increasing duration or concentration of PM_2.5 Inconsistent results were observed for levels of CO, PM₁₀, and SO₂. Conclusion: While an emerging body of literature suggests a potential association between air pollution and thyroid cancer, the quality of evidence is limited by study design constraints, variability in exposure assessment, and inconsistent adjustment for potential confounding factors. The heterogeneity in study designs and methodologies present challenges in interpreting results, underscoring the need for standardized approaches in future research.

Background: Higher center and surgeon volume correspond to better outcomes for patients with thyroid cancer. This study aims to investigate how a hospital's safety-net burden, the proportion of a hospital's patients who are insured by state Medicaid plans or are uninsured, influences the outcomes of high-volume (HV) surgeons. Methods: We performed a retrospective cohort study of all patients who underwent surgery for thyroid cancer in California from 1999 to 2017. We stratified treating facilities by the proportion of Medicaid-type and indigent payors into safety-net burden quartiles. We compared the perioperative and oncologic outcomes of HV surgeons (annual case volume ≥10) for patients undergoing total thyroidectomy across safety-net burden quartiles. A mixed-effects regression model controlled for surgeon random effects and fixed effects of patient and tumor characteristics. Results: Our sample comprised 42,347 patients (78% female, median age 50), of whom 13,848 (32%) were treated by HV surgeons (n = 276). Compared to patients of lower-volume surgeons, patients of HV surgeons were more likely to be White, from the upper quartiles of socioeconomic status and well insured (all p < 0.001). HV surgeons in each hospital's safety-net burden quartile displayed similar case number distributions. Compared to patients treated by HV surgeons at Q1 (lowest safety-net burden) hospitals, those treated by HV surgeons at Q4 (highest safety-net burden) hospitals had higher absolute risks of endocrine complications (+7%, p = 0.007), airway complications (+6%, p = 0.004), disease-specific mortality (+1.3%, p = 0.046), and all-cause mortality during the study period (+3%, p = 0.046) in multivariable analysis. Conclusion: The performance of HV thyroid cancer surgeons differs by a hospital's safety-net burden, with patients treated at high safety-net burden hospitals experiencing higher rates of operative complications, disease-specific mortality, and all-cause mortality. Having a HV surgeon alone may be insufficient to provide optimal short- and long-term outcomes for patients with thyroid cancer.

Background: Isthmic thyroid nodules are more likely to be malignant and isthmic differentiated thyroid cancer demonstrates less favorable behavior compared with lobar locations. The goal of this study was to assess molecular differences of thyroid nodules and carcinomas from the isthmus relative to the lobes. Methods: The Afirma thyroid nodule database (n = 177,227) was assessed for cytologic and molecular differences between isthmus and lobar nodules in this observational cohort study. Genome-wide differential expression analysis was conducted to decipher transcriptomic differences. Histopathology reports (n = 583) of papillary thyroid cancer (PTC) (n = 389) and infiltrative follicular subtype of PTC (IF-PTC) (n = 194) from Afirma discovery cohorts and from thyroid cancer patients managed at an integrative endocrine surgery community care practice were analyzed for molecular differences between isthmic and lobar cancers. Results: In the Afirma database, 8527 (4.8%) isthmus nodules were identified. Bethesda V-VI nodules were almost twice as prevalent from the isthmus as compared with the lobes (8.2% vs. 4.3%, p < 0.0001). Isthmus nodules had twice the frequency of BRAFp.^V600E (21% vs. 10.6%, p < 0.0001), an increased frequency of ALK/NTRK/RET fusions (4.6% vs. 2.5%, p < 0.0001) and SPOP variants (1.5% vs. 0.8%, p < 0.0001), and a lower frequency of NRAS mutations (7.8% vs. 13.2%, p < 0.0001), and PAX8::PPARy fusions (1.1% vs. 2.3%, p < 0.0001) than lobar nodules. Transcriptome analysis of molecular signatures and genome-wide analysis showed that isthmus nodules have higher BRAF-like scores, ERK activity, follicular mesenchymal transition scores (FMT), and lower inflammation activity scores. Pathway enrichment analysis revealed genes downregulated in isthmus tumors are enriched in immune response regulation. IF-PTC from the isthmus (n = 13) were more BRAF-like and had increased ERK and FMT scores compared with those from the lobes (n = 181) (p < 0.01 for all). Conclusions: These data suggest isthmic nodules are more likely to have malignant cytology and increased rates of higher risk molecular alterations compared with lobar nodules. IF-PTC from the isthmus is molecularly different compared with IF-PTC from the lobes. More data are needed to know if a change in surgical therapy is warranted in isthmic thyroid cancers relative to lobar cancers and if this molecular data should influence isthmic thyroid cancer management and monitoring.

Background: Recurrence is a key outcome to evaluate the treatment effect of differentiated thyroid carcinoma (DTC). However, no consistent definition of recurrence is available in current literature or international guidelines. Therefore, the primary aim of this systematic review was to delineate the definitions of recurrence of DTC, categorized by total thyroidectomy with radioactive iodine ablation (RAI), total thyroidectomy without RAI and lobectomy, to assess if there is a generally accepted definition among these categories. Methods: This study adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. In December 2023, a systematic literature search in MEDLINE and EMBASE was performed for studies reporting on the recurrence of DTC, from January 2018 to December 2023. Studies that did not provide a definition were excluded. Primary outcome was the definition of recurrence of DTC. Secondary outcome was whether studies differentiated between recurrence and persistent disease. Two independent investigators screened the titles and abstracts, followed by full-text assessment and data extraction. The study protocol was registered in PROSPERO, CRD42021291753. Results: In total, 1450 studies were identified. Seventy studies met the inclusion criteria, including 69 retrospective studies and 1 randomised controlled trial (RCT). Median number of patients in the included studies was 438 (range 25-2297). In total, 17 studies (24.3%) reported on lobectomy, 4 studies (5.7%) on total thyroidectomy without RAI, and 49 studies (70.0%) with RAI. All studies defined recurrence using one or a combination of four diagnostic modalities cytology/pathology, imaging studies, thyroglobulin (-antibodies), and a predetermined minimum tumor-free time span. The most common definition of recurrence following lobectomy was cytology/pathology-proven recurrence (47.1% of this subgroup), following total thyroidectomy with RAI was cytology/pathology-proven recurrence and/or anomalies detected on imaging studies (22.4% of this subgroup). No consistent definition was found following total thyroidectomy without RAI. Nine studies (12.9%) differentiated between recurrence and persistent disease. Conclusion: Our main finding is that there is no universally accepted definition for recurrence of DTC in the current studies across any of the treatment categories. The findings of this study will provide the basis for a future, international Delphi-based proposal to establish a universally accepted definition of recurrence of DTC. A uniform definition could facilitate global discussion and enhance the assessment of treatment outcomes regarding recurrence of DTC.

Background: Thyroid nodules are challenging to accurately characterize on ultrasound (US), though the emergence of risk stratification systems and more recently artificial intelligence (AI) algorithms has improved nodule classification. The purpose of this study was to evaluate the performance of a recent Food and Drug Administration (FDA)-cleared AI tool for detection of malignancy in thyroid nodules on US. Methods: One year of consecutive thyroid US with ≥1 nodule from Duke University Hospital and its affiliate community hospital (649 nodules from 347 patients) were retrospectively evaluated. Included nodules had ground truth diagnoses by surgical pathology, fine needle aspiration (FNA), or three-year follow-up US showing stability. An FDA-cleared AI tool (Koios DS Thyroid) analyzed each nodule to generate (i) American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) descriptors, scores, and follow-up recommendations and (ii) an AI-adapter score to further adjust risk assessments and recommendations. Four groups were then compared: (i) Koios with AI-adapter, (ii) Koios without AI-adapter, (iii) clinical radiology report, and (iv) radiology report combined with AI-adapter. Performance of the final recommendations (FNA or no FNA) was determined based on ground truth, and comparison between the four groups was made using sensitivity, specificity, and receiver-operating-curve analysis. Results: Of 649 nodules, 32 were malignant and 617 were benign. Performance of Koios with AI-adapter enabled was similar to radiologists (area under the curve [AUC] 0.70 for both, [CI 0.60-0.81] and [0.60-0.79], respectively). Koios with AI-adapter had improved specificity compared to radiologists (0.63 [CI: 0.59-0.67] versus 0.43 [CI: 0.38-0.48]) but decreased sensitivity (0.69 [CI: 0.50-0.83) versus 0.81 [CI: 0.61, 0.92]). Highest performance was seen when the radiology interpretation was combined with the AI-adapter (AUC 0.76, [CI: 0.67-0.85]). Combined with the AI-adapter, radiologist specificity improved from 0.43 ([CI: 0.38-0.48]) to 0.53 ([CI: 0.49-0.58]) (McNemar's test p < 0.001), resulting in 17% fewer FNA recommendations, with unchanged sensitivity (0.81, p = 1). Conclusion: Koios DS demonstrated standalone performance similar to radiologists, though with lower sensitivity and higher specificity. Performance was best when radiologist interpretations were combined with the AI-adapter component, with improved specificity and reduced unnecessary FNA recommendations.

Background: The impact of thyroid dysfunction (TD) on the female reproductive system has been extensively documented. While there is evidence suggesting that alteration in female reproductive status may affect thyroid function, conflicting results have prevented definitive conclusions. This study aimed to investigate the associations of parity, spontaneous abortion (mentioned as abortion throughout this study), and menopause status with the prevalence and incidence of TD. Methods: From the Tehran thyroid study population, 2711 participants were included in the cross-sectional analysis to explore associations between female reproductive status and TD. Overall, 2191 participants with euthyroid were included in the survival study and followed up in 3-year intervals. Multinomial logistic regression was adopted in cross-sectional analysis and multivariable Cox proportional hazard model was used to determine associations between the incidence of TD with parity, abortion, and menopause status, adjusting for age, smoking, body mass index, and thyroid peroxidase antibodies positivity. Results: At the baseline, multiple parities (≥4) were significantly associated with overt hypothyroidism (odds ratio [OR] = 1.12; confidence interval [CI] 1.0-1.26) and subclinical hyperthyroidism (OR = 1.11 [CI 1.03-1.21]). Furthermore, multiple abortions were associated with overt hyperthyroidism (OR = 2.09 [CI 1.02-4.26]). Over the course of the study, multiple parities were significantly associated with the incident subclinical and clinical hypothyroidism. Conversely, a history of abortion was associated with a reduced risk of incident overt hypothyroidism. We found no significant association between menopause status and the prevalence or incidence of either hypothyroidism or hyperthyroidism. Conclusions: Our results suggest that the female reproductive system may be associated with thyroid function. Parity and abortion are associated with the occurrence of TD. A deeper understanding of the underlying mechanisms of the cellular and molecular alterations in signaling cascades during pregnancy is necessary to fully elucidate these associations.

Background: In this narrative review, we assess published data on subclinical hyperthyroidism (SCHyper) and its association with cardiovascular disease (CVD) in the general population. Summary: We present data on the risk of SCHyper in relation to CVD outcomes, including atrial fibrillation (AF), heart failure, stroke, coronary heart disease (CHD), major adverse cardiac events (MACE), CVD mortality, and all-cause mortality. Evidence indicates that SCHyper is associated with an elevated risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. SCHyper appears to have little association with stroke risk and has shown conflicting results regarding CHD risk. Regarding the degree of serum TSH suppression, evidence shows a higher risk of CVD in SCHyper individuals with suppressed TSH (<0.1 mIU/L) compared with those with low TSH (0.1-0.4 mIU/L). Despite evidence that older individuals are inherently at a higher risk for CVD, no studies have yet demonstrated an age-related increase in the relative risk of CVD in SCHyper. Conclusion: The studies indicate that SCHyper is associated with an increased risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. Considering the importance of the degree of serum TSH suppression and age as risk factors for CVD, treatment decisions should be individualized based on their specific risk factors.

Background: Previous Mendelian randomization (MR) studies showed an association between hypothyroidism and cataract and between high-normal free thyroxine (FT4) and late age-related macular degeneration (AMD), but not between FT4, thyroid stimulating hormone (TSH), or hyperthyroidism and diabetic retinopathy or cataract. These studies included a limited number of genetic variants for thyroid function and did not investigate autoimmune thyroid disease (AITD) or glaucoma, include bidirectional and multivariable MR (MVMR), and examine sex differences or potential mediation effects of diabetes. We aimed to address this knowledge gap. Methods: We examined the causality and directionality of the associations of AITD, and FT4 and TSH within the reference range with common age-related eye diseases (diabetic retinopathy, cataract, early and late AMD, and primary open-angle glaucoma). We conducted a bidirectional two-sample MR study utilizing publicly available genome-wide association study (GWAS) summary statistics from international consortia (ThyroidOmics, International AMD Genetics Consortium, deCODE, UK Biobank, FinnGen, and DIAGRAM). Bidirectional MR tested directionality, whereas MVMR estimated independent causal effects. Furthermore, we investigated type 1 diabetes (T1D) and type 2 diabetes (T2D) as potential mediators. Results: Genetic predisposition to AITD was associated with increased risk of diabetic retinopathy (p = 3 × 10^-4), cataract (p = 3 × 10^-3), and T1D (p = 1 × 10^-3), but less likely T2D (p = 0.01). MVMR showed attenuated estimates for diabetic retinopathy and cataract when adjusting for T1D, but not T2D. We found pairwise bidirectional associations between AITD, T1D, and diabetic retinopathy. Genetic predisposition to both T1D and T2D increased the risk of diabetic retinopathy and cataract (p < 4 × 10^-4). Moreover, genetically predicted higher FT4 within the reference range was associated with an increased risk of late AMD (p = 0.01), particularly in women (p = 7 × 10^-3). However, we neither found any association between FT4 and early AMD nor between TSH and early and late AMD. No other associations were observed. Conclusions: Genetic predisposition to AITD is associated with risk of diabetic retinopathy and cataract, mostly mediated through increased T1D risk. Reciprocal associations between AITD, diabetic retinopathy, and T1D imply a shared autoimmune origin. The role of FT4 in AMD and potential sex discrepancies needs further investigation.