BACKGROUND: Among differentiated thyroid carcinoma (DTC) cases, patients classified into the intermediate and high postoperative risk groups for recurrence account for over at least 35% of all cases. However, the optimal management strategy, the clinical utility of radioiodine therapy (RAIT), and the factors determining its efficacy remain insufficiently elucidated. Although the prognostic significance of mutations in BRAF, TERT, TP53, and RAS genes has been well described, their impact on the functional activity of the sodium–iodide symporter (NIS), the degree of cellular differentiation, and the relationship with RAIT responsiveness has not been clearly established.

AIM: To assess the relationship between the mutational profile of the primary tumor and clinical outcomes after RAIT in patients with intermediate/high-risk DTC, and to identify candidate genes associated with poor therapeutic response.

MATERIALS AND METHODS: Next-generation sequencing (NGS) was performed on DNA extracted from formalin-fixed paraffin-embedded (FFPE) samples of primary DTC tumors (N=28). Clinical and anamnestic data of patients meeting inclusion criteria were retrospectively analyzed. The MEDLINE, Google Scholar, and STRING databases were searched for candidate genes implicated in NIS regulation and poor RAIT response. Of the 68 potential genes, 51 distinct mutations were identified in the analyzed samples. Statistical analysis was conducted to evaluate the correlation between clinical characteristics and molecular profiles using Statistica v.12 software (TIBCO Software Inc., USA).

RESULTS: The median follow-up duration was 22.5 [16; 62] months. The median number of somatic variants per patient detected by the targeted sequencing panel was 4.5 [3; 8] (range 1–22). The most frequent variants involved BRAF, PTEN, PIGU, and TG. In the subgroup with unfavorable outcomes, clustering of mutations was observed in BRAF, COL5A1, CTNNB1, DUOX2, AKT1, ALK, ERBB2, GLI1, HORMAD2, IYD, NOTCH3, SLC5A8, SMAD3, and TSHR. The difference in the total number of somatic variants between outcome groups did not reach statistical significance (p=0.755). The presence of distant metastases (M1) emerged as a strong predictor of poor outcome (p<0.001), while coexisting autoimmune thyroiditis had no significant impact (p=0.309).

CONCLUSION: The absence of a significant difference in the number of somatic variants between patients with favorable and unfavorable responses (p=0.755), together with the clustering of pathogenic mutations in specific genes in the radioiodine-refractory group, suggests that the activation of specific oncogenic signaling pathways, rather than overall genomic instability, is a key determinant of tumor behavior in this solid tumor type. Resistance or incomplete response to radioiodine therapy may result from the concurrent activation of multiple oncogenic signaling pathways, including MAPK, PI3K/AKT/ mTOR, TSH–TSH receptor, TGF-β/SMAD3, Sonic Hedgehog, and β-catenin/Wnt signaling. Further evaluation of candidate genes implicated in aggressive disease behavior in differentiated thyroid cancer is warranted in larger patient cohorts, with particular emphasis on transcript-level expression analyses.

BACKGROUND: Ensuring adequate iodine intake in lactating women is critically important for infant brain development. The WHO classifies them as a high-risk group for developing iodine deficiency disorders (IDD). Previously, we identified mild iodine deficiency in pregnant women in the Voronezh region.

AIM: To assess the thyroid status and iodine intake levels in lactating women residing in districts of the Voronezh region with varying levels of iodine consumption among women.

MATERIALS AND METHODS: A cross-sectional cohort study of 100 lactating women (September–October 2024) included a questionnaire, physical examination, and measurement of thyroid-stimulating hormone (TSH), anti-thyroid peroxidase antibodies (Anti-TPO), selenium, and zinc in blood, urinary iodine (cerium-arsenite method), and breast milk iodine (mass spectrometry), as well as rapid testing of salt for iodine.

RESULTS: Iodized salt was used by 17% of households; 16% of women used it regularly; iodine supplements were taken by 12%; iodine-rich foods were consumed by 9%. The median urinary iodine concentration (mUIC) was 62.9 μg/L (normal ≥100 μg/L). The median breast milk iodine concentration was 37.77 μg/L (normal 100–200 μg/L). The median TSH was 1.425 mIU/L; thyroid dysfunction was found in 7%; Anti-TPO positivity in 14%. Selenium and zinc levels were in the lower tertile of normal. A moderate positive correlation was found between urinary and breast milk iodine (ρ=0.48; p=0.032).

CONCLUSION: Lactating women in the Voronezh region exhibit pronounced iodine deficiency and critically low breast milk iodine content, posing a threat to infant cognitive development. Systemic iodine prophylaxis measures are urgently needed.

Graves’ disease is a systemic autoimmune process characterized by persistent breakdown of immune tolerance and continued presence of thyrotropin receptor autoantibodies (TRAb), even after radical thyroidectomy. This review examines the role of the “gut–thyroid axis” as a key regulator of systemic immune homeostasis. Particular attention is paid to short-chain fatty acids (SCFAs) — microbial metabolites that act as potent epigenetic modulators. The mechanisms of histone deacetylase (HDAC) inhibition by butyrate and propionate are described in detail, which promote stabilization of Foxp3 gene expression in regulatory T cells and suppression of B-lymphocyte differentiation factors (AID, Blimp-1). The interplay between intestinal dysbiosis, increased barrier permeability, and uncontrolled autoantibody production is analyzed. In conclusion, prospective targeted therapeutic strategies are discussed, fecal microbiota transplantation (FMT), and the use selective HDAC inhibitors aimed at restoring immune control in refractory forms of the disease.

In June 2025, updated clinical guidelines for the diagnosis and management of thyrotoxicosis were released in the Russian Federation, developed on the basis of current scientific evidence, real-world clinical practice, and international standards. The document highlights the most significant and conceptual shifts — both in diagnostic algorithms and therapeutic strategies — including priorities in pharmacological treatment, and criteria for surgical intervention and radioiodine therapy. A comparative analysis reveals the evolution of clinical reasoning and the ongoing standardization of care for patients with thyrotoxicosis in contemporary endocrinology.

The aim of this review is to enhance clinicians’ awareness and promote a critically informed, balanced, and personalized approach to implementing these clinical guidelines in the diagnosis and treatment of thyrotoxicosis.