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.
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.
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.
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.
This review focuses on the regulation and practice of iodine supplementation (IS) use with a focus on Eastern/Central European and Central Asian (ECE-CA) countries, based on new evidence on the benefits and harms of IS use depending on the salt iodization status. Information on IS use was analyzed for population groups particularly vulnerable to iodine deficiency: pregnant and lactating women, infants aged 6–36 months, and preschool and school-age children. The review preparation process included several repeated searches using PubMed and other sources. Open access articles published in English, Russian, and Romanian over the past 10–15 years were included in the analysis. Analysis of available sources showed that 9 ECE-CA countries had official recommendations on IS use in different population groups, usually pregnant and lactating women. However, in 5 of them, the median urinary iodine concentration in pregnant women was below the optimal level (150 μg/L). Experience in the ECE-CA region shows that mandatory salt iodization ensures adequate iodine intake for all population groups. Further efforts should be aimed at increasing the use of iodized salt to cover more than 90% of households and expanding the use of iodized salt in food production. However, IS may still be necessary for individuals at risk of iodine deficiency due to dietary and lifestyle factors (vegan/vegetarian and other restrictive diets). Such targeted use of IS requires the development of official guidelines to assess the effectiveness of this approach and methods for monitoring its implementation.
The article comments on the possible cause for the discrepancy between low knowledge about the use of iodized salt in households and the optimal iodine status of schoolchildren in Novosibirsk, Russia, and discusses possible hidden sources of iodine in the diet.
Today, replacement therapy with sodium levothyroxine (L-T4) is the main method of treating hypothyroidism. Replacement therapy with tablet forms of L-T4 is simple, understandable and convenient. However, a significant proportion of patients are in a state of iatrogenic thyrotoxicosis or uncompensated hypothyroidism. The reasons for unsatisfactory compensation are both violations of the pill regimen, including missed doses, and lifestyle, comorbid conditions or drugs received by the patient that interfere with the selection of the optimal dose. Today, not only tablets are used in the world, but also other forms of L-T4, for example, an oral solution and gel capsules. In March 2024, a liquid levothyroxine drug was registered in Russia. In this article, we will consider the practical features of prescribing this drug and its differences from tablet forms.
In the summer of 2024, the next issue of The Thyroidologist magazine was published. In order to keep readers up to date with the latest research in the field of thyroidology, Luca Persani (editor-in-chief of the European Thyroid Journal) has selected several recent articles for publication in The Thyroidologist journal. These articles will be discussed in this publication.
BACKGROUND: For thyrotoxicosis, thyroid enlargement and the presence of nodules are considered to be the leading clinical criteria. The ultrasound method allows to assess these two criteria and additionally the echogenicity of the gland. AIM: to find out the state of three ultrasound criteria - echogenicity, size and structure of the thyroid gland in thyrotoxicosis. MATERIALS AND METHODS: The data of echogenicity, size and structure of thyroid gland in 3633 patients with thyrotoxicosis were analysed. The mean age was 48.10±14.08 years, men — 721, women — 2912. Ultrasound studies were performed in B-mode. The upper criterion of the norm of the gland size for women was considered to be the volume of 18 cm3, for men — 25 cm3. The sizes exceeding the specified volumes were considered as pathological. Echogenicity of the gland was compared with parotid salivary gland and divided into normal and pathological criterion. The structure of the thyroid gland was divided into normal and pathological. The criterion of structure pathology was the presence of single or multiple volumetric formations. Ultrasound criteria were divided into simple and combined types. If one criterion was classified as pathological, while the other two remained normal, this situation was considered as a simple type of pathology. If two or three criteria changed simultaneously, the pathology type was labelled as combined. RESULTS: a simple type of echogenicity pathology was observed in 19.5% of cases, size in 0.8%, and structure in 1.2%. Combined pathology of echogenicity and size was observed in 69.1% of cases, echogenicity and structure in 29.1%, size and structure in 24.6%. Combined pathology of all three criteria was observed in 23.0% of cases. In 1.3% of thyrotoxicosis cases, all three ultrasound indicators remained within normal limits. A subtype of echogenicity pathology is characterized by diffuse (56.7%) and localized (38.1%) reductions. The mean area of localized echogenicity reduction was 37.12±12.43%. CONCLUSION: the leading ultrasound manifestation of thyrotoxicosis was changed in echogenicity, followed by changes in size, and then structure.
Levothyroxine (L-T4) is a drug with a narrow therapeutic range. Even a small change in the dose can lead to its deficiency or overdose. Existing tablet forms of L-T4 with a wide range of dosages ensure the achievement and maintenance of euthyroidism in many patients. At the same time, patients with hypothyroidism are often decompensated. Today, not only tablets are used in the world, but also other forms of L-T4, including gel capsules and liquid form. The presented review discusses the pharmacokinetics, advantages and disadvantages of the different forms of L-T4. Factors affecting the bioavailability of L-T4 drugs are also discussed.
The history of radionuclide diagnostics began with the first experiments on radioactive isotopes at the beginning of the 20th century. The introduction of radioactive isotopes of iodine and technetium into thyroid diagnostics and treatment was the start of the development of all nuclear medicine and theranostics. The hardware for nuclear medicine has come a long way from simple Geiger-Muller counters to modern machines with molecular imaging capabilities PET and SPECT. Nuclear thyroidology today is an important applied tool for high-tech diagnostics and treatment of thyroid diseases.
Multiple endocrine neoplasia syndrome type 1 (MEN-1) is an inherited disorder associated with mutations in the MEN1 gene and characterized by the «classic triad»: involvement of the parathyroid gland, pancreatic islet cells and anterior pituitary. The penetrance of primary hyperparathyroidism (PHPT) in MEN-1 reaches 90-100% with age. Primary hyperparathyroidism in MEN-1 is associated with polyglandular lesions, and tumors do not always develop synchronously, leading to a high incidence of disease recurrence after surgery. In MEN-1-associated PHPT, hyperplasia is most common and multiple adenomas are less common. The growth of hyperplastic cells may be diffuse, nodular or diffuse-nodular, which complicates the differential diagnosis between adenoma and diffuse-nodular hyperplasia with the presence of a single dominant nodule. Carcinomas and atypical tumors in MEN-1 are casuistically rare. We present the unique case of a young patient with a germline mutation in the MEN1 gene (c.684dup) and clinically «aggressive» course of PHPT due to atypical parathyroid tumors.
Papillary Microcarcinoma of the Thyroid Gland (PMTC) is the most common type of malignant thyroid neoplasm, characterized by its small size and generally favorable prognosis. The increased detection rate of PMTC is associated with advancements in high-precision diagnostic methods such as ultrasound and fine-needle aspiration biopsy. Diagnostic approaches include the use of the EU-TIRADS and Bethesda systems for risk assessment, as well as the analysis of molecular markers, such as BRAF gene mutations and promising studies on the role of microRNAs in predicting tumor progression.Optimal management of patients with PMTC requires an individualized therapeutic approach due to differences in disease progression. This article analyzes current diagnostic and treatment methods for PMTC, including the use of molecular-genetic markers, minimally invasive technologies, and active surveillance strategies, with an emphasis on a personalized approach to prognosis and therapy.
Thyroiditis in children are important issues of pediatric endocrinology due to their widespread occurrence. They differ in etiology, pathogenesis, and their clinical manifestations. Updated clinical guidelines in 2024 are the main working tool of physicians. They briefly and structurally present the main information about epidemiology and modern classification of thyroiditis, methods of diagnosis and treatment based on the principles of evidence-based medicine.
The lack of systemic mass iodine prophylaxis in the Russian Federation is the main reason for the annual increase in the inci dence of thyroid pathologies throughout the country. Despite the set of measures aimed at implementing the Strategy for Improving the Quality of Food Products in the Russian Federation (RF) until 2030, approved by the RF Government Decree of 29.06.2016 No. 1364, including providing for the supply of iodized salt to retail organizations, food units of healthcare institu tions, kindergartens, schools and other institutions, the prevalence of thyroid pathologies in the regions remains high. The arti cle presents the results of the study assessing the severity of iodine deficiency and the prevalence of thyroid pathology among the population of the Tula region, conducted by specialists of the “Endocrinology research center” of the Ministry of Health of Russia together with the Ministry of Health of the Tula Region.BACKGROUND: The relevance of research on the assessment of iodine status and the study of the structure of thyroid pathol ogy among residents of certain territories of the Russian Federation, which are characterized by natural iodine deficiency and past technogenic radiation contamination, is associated with the need to clarify the mechanisms of development of thyroid pathology, including comorbid conditions, and will allow the implementation of scientifically justified preventive measures. AIM: To conduct a comprehensive study to assess the current iodine sufficiency of the population of the Tula region — an area affected by the Chernobyl nuclear power plant accident in 1986, analyze the actual prevalence and structure of thyroid pathol ogy compared to official statistics, and formulate conclusions about necessary preventive measures.MATERIALS AND METHODS: During the study in the Tula region, 589 people were examined, including 303 school-age chil dren (7–11 years old) and 286 adults (18 years and older). The epidemiological part of the study was conducted among the child population using the cluster method in three districts of the region (Tula — 90 children, Arsenyevsky district — 118 children, Yasnogorsky district — 95 children) and included: collection of anamnesis and questionnaires, measurement of anthropomet ric indicators (height, weight), examination by an endocrinologist with palpation of the thyroid gland, thyroid ultrasound with volume calculation, determination of iodine concentration in urine, examination of samples of table salt from households for the presence of iodine in them. A cross-sectional cohort survey of the adult population was conducted from June 8 to 10, 2022, in three districts of the Tula region: Yasnogorsk (n=79), Arsenyevsky (n=70), Shchekinsky (n=137) and included: collection of anamnesis and questionnaires, examination by an endocrinologist, thyroid ultrasound, determination of thyroid-stimulating hormone (TSH) and thyroid peroxidase antibodies (TPO-AT) in the blood serum, as well as a study of samples of table salt from households for the presence of iodine. RESULTS: According to the results of the epidemiological study in the Tula region, mild iodine deficiency (ID) was established (median urinary iodine (mUI) — 69.1 μg/l, share of diffuse goiter in children according to ultrasound data — 8.5%), with the allocation of the Arsenyevsky district, in which the mUI of 41.5 μg/l indicates moderate ID and a large proportion of goiter in children was detected — 13.5%. The share of households in the Tula region using iodized salt is very low — 18.5%. The results of the examination of the adult population of the Tula region confirmed the high prevalence of thyroid pathology in the region (ultrasound signs of structural changes in the thyroid gland were detected in 52.8% of those examined), which is mostly rep resented by nodular forms of goiter (76.8%). The combination of ultrasound signs of autoimmune and nodular thyroid pathol ogies occurs in 11.3% of cases of the overall prevalence of structural changes in the thyroid gland. When comparing with the data from previously conducted expeditions, a negative dynamics has been noted in the form of an increase in the prevalence of diseases of the thyroid glands detected by ultrasound in the study areas, from 26% in 1995 to 65–85.7% in 2022.CONCLUSION: Monitoring of the epidemiological situation in the Tula region has demonstrated a persisting inadequate level of iodine sufficiency among the population, which is reflected in the increasing prevalence of thyroid diseases and indicates the inefficiency of episodic measures for preventing iodine deficiency disorders (IDD). Taking into account the ecological status of the region, from the standpoint of medical and social significance, it is extremely important for regional health authorities to take urgent measures, namely, the development and implementation of a regional target program for the prevention of IDD with an emphasis on mass prevention using iodized salt.
