Signal transducer and activator of transcription 3 (STAT3) is a signaling molecule that functions downstream of various cytokine and growth factor receptor signaling pathways to regulate cell growth, survival, and differentiation. Constitutive activation of STAT3 is relevant to cancer development and progression in many types of malignancies. In this study, the relationship between STAT3 activation and the prognosis of papillary thyroid carcinoma (PTC) was retrospectively examined using immunohistochemical staining with an anti-STAT3 antibody.

Patients with resistance to thyroid hormone β (RTHβ) show elevated thyroid hormone concentrations with non-suppressed thyroid-stimulating hormone (TSH) concentrations and large phenotypic variability. Triac therapy has been successfully applied in some patients. Mosaic mutations causing mild RTHβ have been reported three times so far.

Thyroid hormones (TH) are well-known regulators of the immune system. However, the precise immunomodulatory mechanisms of TH action in immune cells remain elusive. In a previous study, an essential role of the TH receptor α (TRα) in regulatory T cell (Treg) immunity was demonstrated, affecting Treg activation at steady state. The present study therefore aimed to unravel the biological relevance of altered TRα action in protective immune responses during disease.

This review examines the emerging roles of DICER1 and DGCR8, key components of the miRNA biogenesis pathway, in thyroid pathogenesis, with a particular focus on their association with oncocytic morphology. Recent findings have expanded our understanding of DICER1 syndrome and DGCR8-related thyroid disorders, revealing a broader spectrum of thyroid lesions associated with mutations in these genes than previously recognised. We analyse the current literature on DICER1 and DGCR8 mutations in thyroid pathology, synthesising data from both basic science and pathological studies. The review explores recent findings on oncocytic features in some DICER1-mutated thyroid lesions, acknowledging that this association remains under investigation. The manuscript details the molecular mechanisms underlying DICER1 and DGCR8 mutations, including their impact on miRNA processing and subsequent effects on gene expression and cellular function. We discuss the diverse range of thyroid lesions associated with these mutations, from benign follicular nodular disease to aggressive carcinomas. The clinical implications of these findings are significant, as recognising DICER1 and DGCR8-related thyroid lesions can lead to improved patient management, including genetic counselling and surveillance for other associated malignancies. We propose an algorithm for identifying DICER1-related thyroid lesions, with a focus on oncocytic tumours, to aid clinicians and pathologists in recognising these entities. This emerging field promises to refine the diagnosis, management, and treatment of thyroid disorders associated with miRNA biogenesis pathway alterations, potentially leading to novel diagnostic and therapeutic approaches.

Cryo-EM studies indicate that full-length human TSH receptor (TSHR) is a monomer consisting of a leucine-rich repeat (LRR) domain (LRD), hinge region (HR) and transmembrane domain (TMD). Receptor autoantibodies (TRAb) bind to the extracellular domain (LRD plus HR). In the cell membrane, TSHR transitions between inactive and active states, involving rotation of the LRD about the HR, with the active state LRD further from the membrane. Cryo-EM structures of the TSHR in complex with different human monoclonal autoantibodies provide a detailed understanding of how they interact with the receptor. Stimulating monoclonal autoantibody M22™ binds to the entire LRD (LRR 1-11) concave surface and cannot interact with the inactive state receptor, as this would result in a clash between antibody and membrane. No clash occurs when M22™ binds the active state, and once bound, M22™ holds the receptor in the active state, resulting in prolonged activation. K1-18™, a different stimulating monoclonal autoantibody, interacts with LRR 1-11 in a similar way to M22™. Blocking type monoclonal autoantibody K1-70™ only interacts with LRR 1-7, positioning itself clear of the cell membrane when interacting with inactive or active receptor states. Once bound, binding of TSH and other TRAb is prevented. Monoclonal autoantibody 5C9™ interacts differently, binding the inactive conformation from LRR 3 to the HR. Its heavy chain CDR3 interacts with the HR, locking the receptor in the inactive state, causing inhibition of constitutive activity, activating mutation activity and blocking receptor binding by TSH and TRAb. Elucidation of the structure of the TSHR and mechanisms of its activation and inactivation by TRAb is of great importance for the development of new TSHR-specific drugs.

Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are both rare and aggressive thyroid cancers. Advances in targeted therapy and immunotherapy have changed treatment strategies and improved prognosis in these patients.

Previous studies showed that dynamic risk stratification (DRS) was also useful in differentiated thyroid carcinoma patients with lobectomy or total thyroidectomy without radioactive iodine. The aim of this study was to evaluate the DRS system in patients with follicular thyroid carcinoma (FTC) who underwent lobectomy alone.

Subclinical hyperthyroidism (SHT), a low serum thyroid-stimulating hormone (TSH) and normal free thyroxine (FT4) concentration, has potential health implications yet the epidemiology and factors influencing its natural course in a primary care setting remain unclear.

Autoimmune hypothyroidism occurs rarely before three years of age. Two siblings were diagnosed with autoimmune hypothyroidism at age five and 16 months, presenting with classic symptoms of hypothyroidism, abnormal thyroid function tests (TSH 200 and 660 mU/L; reference 0.73-8.4 mU/L; Free T4 5.9 and <1.3 pmol/L; reference 11.9-25.6 pmol/L), and high thyroid peroxidase antibody levels. Thyroxine medication alleviated their symptoms. Apart from mild infections, the siblings exhibited no other major disorders. Whole exome sequencing identified a pathogenic STAT3 gain-of-function variant, most commonly associated with infantile-onset multi-organ autoimmune disorder. Genetic testing for early-onset hypothyroidism may reveal specific etiologies, impacting follow-up and treatment.

This study aims to analyze the genes that influence PTC progression, and investigate the role of MAPK13 in PTC.

In 2021 the European Group on Graves' Orbitopathy (EUGOGO) published clinical practice guidelines for the management of GO, and in 2022 the American and European Thyroid Associations published the ATA/ETA consensus statement on the same topic.

To compare the diagnostic test accuracy of Afirma GSC and ThyroSeq v3 in cytologically indeterminate thyroid nodules.

Papillary thyroid carcinoma (PTC) has an excellent prognosis, yet recurrence remains a clinical concern. Patients at intermediate risk may benefit from additional prognostic markers. We aimed to evaluate whether tumor desmoplasia predicts recurrence in intermediate-risk PTC patients and to assess its prognostic clinical utility.

Observational studies in adults suggest that incidental PTC (iPTC) and non-incidental PTC (niPTC) are distinct entities. We examine the incidence of iPTC in pediatric patients undergoing thyroidectomy for benign conditions and compare clinical and histopathologic findings, and outcomes, of iPTC with those of niPTC.

Persistent Graves' disease (GD) after total thyroidectomy is sporadic and may be explained by incomplete total thyroidectomy, GD in ectopic thyroid tissue (ETT) or struma ovarii.

Thyroid cancer is the most prevalent endocrine malignancy. Distinct genetic alterations drive the development and progression of thyroid tumors of follicular cells with remarkable genotype-phenotype correlation. In most tumors of follicular cell origin, the primary molecular events are RAS or RAS-like (follicular-patterned tumors) and BRAF p.V600E or BRAF V600E-like (conventional papillary carcinomas) alterations. Progression of thyroid tumors to advanced and less-differentiated carcinomas requires additional oncogenic alterations, including TP53 and TERT promoter mutation, and aberrant PI3K-PTEN-AKT signaling. Understanding the genetic landscape of thyroid carcinoma of follicular cells is essential to optimize clinical management and to identify molecular targets to treat cases with aggressive disease refractory to standard radioactive iodine therapy. What follows is a comprehensive and updated outline of the main somatic genetic and molecular alterations in thyroid carcinoma of follicular cells.