Thyroid Gland

Per- and polyfluoroalkyl substances (PFAS) may disrupt thyroid hormones although the literature shows mixed evidence of this effect and exposure to mixtures of PFAS remains poorly understood. We used the Michigan PFAS Exposure and Health Study cohort to examine linear and nonlinear associations between serum PFAS concentrations, both alone and as a mixture, and serum thyroid hormone concentrations. Study participants included 728 adolescents and adults living in an area with past PFAS contamination of drinking water. We quantified 39 individual PFAS and four thyroid hormones in serum from participants between the years 2020 and 2021. Linear regression, weighted quantile sum (WQS) regression, supervised Principal Component Analysis (PCA), and Bayesian Kernel Machine Regression (BKMR) were used. When analyzed individually, a 1% increase in PFUnA serum concentrations was associated with a 0.023% decrease in TT3 concentration (95% CI: -0.04%, -0.01%, p < 0.05). All three mixture analyses consistently indicated an inverse relationship between PFAS mixtures and TT3 concentrations: (1) a one standard deviation increase in the WQS of the PFAS mixture was associated with a 2.0% decrease in TT3 concentration (95% CI= -4%, 0%, p < 0.05) adjusting for covariates, (2) using PCA, one standard deviation increase in a PFAS mixture was associated with a 1.2% decrease in TT3 (95% CI: -2.1%, -0.4%), and (3) BKMR similarly suggested a negative association between the PFAS mixture and TT3. We observed cross-sectional associations between a mixture of serum PFAS concentrations and thyroid hormone dysregulation, largely manifesting as decreased TT3 serum concentrations.

Micronutrients and environmental factors are key exogenous agents influencing thyroid DNA integrity. Micronutrients act as cofactors in DNA replication, repair, and antioxidant defence, while environmental exposure, such as radiation, heavy metals, and endocrine-disrupting chemicals, can directly damage DNA, leading to genomic instability. Although many studies have confirmed the link between micronutrient status and thyroid health, the effects of nutrient imbalances and environmental stressors on thyroid DNA remain underexplored. This narrative review examines how these factors may compromise thyroid genome stability and contribute to disease development. The analysis focused on the roles of iodine, selenium, iron, zinc, copper and vitamins D, B9, and B12 as well as environmental exposures such as radiation, heavy metals, and endocrine-disrupting chemicals. The findings suggest that both micronutrient imbalance and environmental stress can impair DNA integrity in thyroid cells. Understanding these complex relationships is critical for developing effective strategies to maintain thyroid health and mitigate the risk of thyroid diseases associated with compromised genomic integrity. Methodology: This narrative review was based on 254 articles retrieved through a manual search of the PubMed and Google Scholar databases, covering the years 2000-2025 and focusing on the influence of micronutrients and environmental factors on thyroid DNA integrity and repair. Several seminal earlier publications, fundamental to a comprehensive understanding of the topic, were also included.

Thyroid nodules represent a common clinical challenge, with 20-30% of fine-needle aspiration biopsies yielding indeterminate cytology results that complicate management decisions. While fine-needle aspiration cytology (FNAC) remains the gold standard for initial evaluation, up to 30% of cases produce indeterminate results, often leading to unnecessary diagnostic surgeries. This comprehensive review examines the transformative role of molecular diagnostics in thyroid pathology, focusing on their clinical utility, prognostic implications, and future directions. Molecular testing platforms, including Afirma GSC, ThyroSeq v3, and ThyroidPrint, have transformed the management of indeterminate thyroid nodules through gene expression profiling, mutation analysis, and microRNA signatures. The third-generation tests exhibit high sensitivity (91-100%) and negative predictive values (90-100%), thereby enabling surgical avoidance rates of 50.3-68.6% for patients with indeterminate cytology. The platforms employ both "rule-out" strategies (high sensitivity/NPV) and "rule-in" approaches (high specificity/PPV) to guide clinical decision-making. The paradigm of classifying thyroid tumors based on BRAF-like and RAS-like molecular profiles is becoming increasingly entrenched in clinical and diagnostic practice, affording pathologists and clinicians the ability to render diagnoses that are both more precise and reproducible. Within this molecular framework, the identification of markers such as TERT promoter and TP53 mutations, along with gene fusions, provides not only refined prognostic information but also facilitates the selection of patients for targeted therapeutic regimens including BRAF/MEK inhibitors and RET inhibitors. Nevertheless, the implementation of these advances is not without its impediments. The field continues to grapple with platform heterogeneity, economic constraints, and geographic disparities affecting access to comprehensive molecular diagnostics-factors that necessitate ongoing efforts to standardize testing and expand global availability. The future of this field is marked by several key developments, including the expansion of next-generation sequencing, the advancement of liquid biopsy technologies, the integration of artificial intelligence, and the adoption of multi-omic approaches. International guidelines are increasingly recommending molecular testing for advanced thyroid cancers and indeterminate nodules. These guidelines emphasize the need for standardized protocols and equitable access to such testing. Molecular diagnostics should be embraced as complementary tools within multidisciplinary care to optimize patient outcomes while reducing unnecessary interventions in thyroid nodule management.