Given the socio-economic, political and epidemiological changes in the regions of the Russian Federation, the issue of modernizing the training of medical personnel and planning to provide medical organizations with qualified specialists has remained extremely important for several years. The analysis of the survey showed that at present the highly topical issue of staffing the population with endocrinologists and pediatric endocrinologists does not have an unambiguous effective solution. The above measures to reorganize the educational environment require additional revision and correction for the most effective work in the field of medical education. Ultimately, these activities will have an impact on improving the level of training of specialists, improving the personnel situation in the constituent entities of the Russian Federation and improving the quality of medical care for the population of the country.

BACKGROUND: The diagnostic value of calcitonin measurement in fine-needle aspiration biopsy wash-out fluid is a promising tool in the diagnosis of medullary thyroid cancer.

AIMS: We assessed the potential usefulness and the diagnostic significance of Ct-FNAB alone in comparison with cytology in the diagnosis and localization of primary or metastatic MTC.

MATERIALS AND METHODS: For this purpose, we retrospectively examined data from 67 patients with suspicious thyroid nodules and/or lymph nodes who ultimately underwent surgical treatment at the Endocrinology Research Centre in 2015–2020. The primary endpoint of the study was to evaluate the diagnostic accuracy of Ct-FNAB when compared to cytological examination. The secondary endpoint was to determine the optimal diagnostic level for use in clinical practice.

RESULTS: The obtained results showed that high Ct-FNAB concentrations were present in all histologically proven MTC, either in thyroid gland (sensitivity 92.5%, specificity 100%) or neck masses (sensitivity 88.5%, specificity 100%). The optimal diagnostic threshold for Ct-FNAB values from thyroid nodes was > 122 pg/ml, from lymph nodes >35.8 pg/ml.

CONCLUSIONS: Our findings suggest that Ct-FNAB is a highly reliable diagnostic procedure to identify primary and recurrent/metastatic MTC. The actual relevance of this technique in the management of MTC needs further longitudinal studies in a larger number of patients.

BACKGROUND: Clinical diagnostic laboratories (CDL) have at their disposal various automated systems for the measurement of biochemical parameters and markers such as prolactin. Each of the test systems manufactures offers its own alternate design of the method, which makes standardization difficult. In endocrinological practice, the problem of result discrepancies often arises. In hormonal assays, the clinical picture of patients sometimes does not correspond to the reference values provided by the manufacturers, which determines the need to develop the method-specific reference values for a specific population. The difficulty in interpreting basal prolactin levels is not only due to a transient increase in the hormone levels caused by stress or excessive physical exertion, but also due to a significant variability of indicators in the same patient, even if all recommendations for blood sampling are followed.

AIM: The aim of the study to determine the reference values in serum samples of women, men and children of different age groups for the VITROS Immunodiagnostic Systems and compare the results with the “expected prolactin levels” recommended by the method manufacturer

MATERIALS AND METHODS: The monocentric study included 879 serum samples of apparently healthy subjects who were admitted to the Endocrinology Research Center. Measurements were performed using the VITROS ECi 3600 automatic chemiluminescence analyzer (Ortho-Clinical Diagnostics, Great Britain).

RESULTS: For adult men and women reference values were 66–436 and 94–500 mIU/l respectively. When comparing the results of prolactin determination in women and men of the studied cohort with the “expected values” of the VITROS ECi 3600 manufacturer a systematic shift towards an increase in lower and upper limits of the reference values was found in both ­cohorts.

CONCLUSION: The obtained reference values of prolactin can be use in the determination of prolactin in the Russian population for VITROS ECi 3600 Immunodiagnostic Systems.

BACKGROUND: Sporadic multiple parathyroid gland disease is ¼ cases of primary hyperparathyroidism (PHPT). However, a single tactic for diagnosing and operating volume in patients with this variant of PHPT has not yet been developed. One of the possible directions in the search for pathogenetically substantiated methods of diagnosis and treatment is the study of the molecular genetic features of the disease and associated clinical and laboratory factors.

AIM: To study the features of the expression of calcium sensitive (CaSR) and vitamin D (VDR) receptors on the surface of parathyroid cells in primary hyperparathyroidism with solitary and multiple lesions of the parathyroid glands, as well as its changes under the influence of a decrease in the filtration function of the kidneys.

MATERIALS AND METHODS: In a single center observational prospective study with retrospective data collection, there were patients who during 2019–2021. operated on for PHPT, secondary hyperparathyroidism (SHPT) and all cases of tertiary hyperparathyroidism (THPT) operated during 2014–2021. The expression of CaSR, VDR and its relationship with the main laboratory parameters, the clinical variant of hyperparathyroidism, and the morphological substrate were studied.

RESULTS: The study included 69 patients: 19 with multiple and 25 with solitary PTG near PHPT, 15 with SHPT, 10 with THPT. A statistically significant decrease in the frequency of detection of normal expression of CaSR and VDR receptors occurs in any morphological variant of hyperparathyroidism and is observed in 93–60% of drugs. A decrease in the normal expression of CaSR in hyperplasia is detected statistically significantly less frequently than in adenoma (p≤0.01). The median expression intensity in adenoma was 2.5 (2:3), in hyperplasia 3.5 (3–4) (p≤0.01). The difference in the molecular mechanisms of the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma (PHPT with solitary adenoma) or hyperplasia (SHPT and PHPT with multiple PTG lesions) is realized in the frequency of maintaining normal CaSR expression in the PTG tissue. These mechanisms are implemented at the local level, their variability does not change under the influence of RRT. A common molecular genetic mechanism for the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma or hyperplasia has been found to reduce the frequency of maintaining normal VDR expression in PTG (up to 7–13%), p<0.01. This mechanism is implemented at the local level, its variability changes under the influence of RRT, reaching statistically significant differences in patients with THPT.

CONCLUSION: The study demonstrates the features of changes in the expression of CaSR and VDR in PHPT with multiple lesions of the parathyroid glands. The relationship between the expression of these receptors and the clinical variant of hyperparathyroidism, the morphological substrate, the main laboratory parameters, and renal function was shown.

BACKGROUND: The content of regulatory T cells (Treg) at different stages in formation of effector subpopulations and the level of CD25 expression on the membrane of their various fractions in Graves’ disease can determine the long-term autoimmune process persistence and be the target of immunotropic therapy of the disease.

AIM: To study the features of regulatory T-blood cells subpopulation and the level of CD25 expression in patients with Graves’ disease in dynamics after radioactive iodine therapy (RIT) to identify the specific Treg subpopulations for potential immunotropic therapy targets of the disease.

MATERIALS AND METHODS: A single-center, prospective, cohort, open, controlled study was conducted with the participation of women with laboratory-confirmed Graves’ disease. The features of regulatory T-blood cells subpopulation and the level of expression (MFI) CD25 surface receptor were studied by flow cytometry using direct immunofluorescence using monoclonal antibodies.

RESULTS: The study included 36 women with recurrent Graves’ disease, middle age 46.34±14.32 years. In patients with Graves’ disease before and during the entire period after RIT a low percentage of naive (CD45R0-CD62L+) and terminally differentiated (CD45R0-CD62L-) Treg was established relative to the control, and on 3 and 6 months after RIT a significant decrease of cells with this phenotype was revealed relative to the values detected in patients before and 1 month after RIT (p<0.001). Against the background of compensated hypothyroidism the most significant changes of expression CD25 receptor in patients with Graves’ disease were found on 3 and 6 months after RIT: reduced levels of MFI CD25 on surface of naive and terminally differentiated Treg.

CONCLUSION: A decrease in the level of naive Treg was found (apparently due to a violation of differentiation processes in thymus) and terminally differentiated Tregs (due to maturation and survival processes), which are supplemented by a reduced expression of the CD25 receptor on the surface of these cells and do not depend on hyperthyroidism compensation, the titer of TSH receptor antibodies, previous conservative therapy with thiamazole and RIT. The obtained new data reveal the role of naive and terminally differentiated Treg subpopulations in immunopathogenesis and help to outline further ways to develop approaches for immunotropic therapy.

Prolactinomas are the most common secreting adenomas of the pituitary. In 20% of cases resistance to dopamine-agonists treatment is observed. Medical therapy resistance causes progression of pathological symptoms of hyperprolactinemia and negative topographic and anatomical changes of prolactinoma. The causes of ineffectiveness of dopamine agonists therapy are not fully understood as well as approaches to managing patients require clarification. Current concepts of resistance are based on the data obtained as a result of surgery or after a period of long-term ineffective therapy. Thus, it is very important to find methods of assessing the sensitivity of prolactin-secreting adenomas to drug therapy before surgical treatment. Genetic and immunohistochemical studies find special place among these methods, making it possible to predict adenoma’s response to drug therapy at early diagnostic stage. Obtained results will allow us to form personalized algorithm for managing patients.

Multiple sclerosis (MS) is a severe chronic autoimmune demyelinating disease of the central nervous system, mediated by Th1/Th17 lymphocytes as well as B lymphocytes, macrophages and other immune cells. Some patients with MS are treated with alemtuzumab, a monoclonal antibody against CD52+ cells, which belongs to the disease-modifying therapies (DMTs). The main effect of alemtuzumab is related to changes in immune recruitment. Alemtuzumab therapy can induce secondary autoimmunity against the background of immune rebalancing. The thyroid gland is generally involved in the autoimmune process. Graves’ disease (GD) develops most often, followed by autoimmune thyroiditis.

We present a clinical case of a patient with GD developed after alemtuzumab therapy for MS. The patient was referred to a radiologist at the Department of Radionuclide Therapy of Endocrinology Research Centre for radioiodine therapy (RAIT) due to relapse of thyrotoxicosis after anti-thyroid drug therapy for GD. The goal of treatment was achieved in 2 months, thyroid hormone therapy was initiated, against the background of this, there was compensation of thyroid function.

BACKGROUND: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is characterized by bilateral benign adrenocortical lesions, which in some cases lead to Cushing syndrome (CS). Due to the low detection, non-specific, erased clinical picture and slow, long-term progression, it is difficult to assess the true prevalence of PBMAH. This also leads to fairly limited literature data. A detailed analysis of biochemical, imaging parameters, the clinical presentations, in particular, an assessment of the course of comorbidities (arterial hypertension (AH), diabetes (DM), osteoporosis), is necessary to develop an algorithm for managing patients with PBMAH.

AIM: Analysis of clinical and laboratory characteristics of patients with various forms of PBMAH.

MATERIALS AND METHODS: A single-center, retrospective, observational, cross-sectional study was carried out. This study included 110 patients with PBMAH who got referred to the National Research Center for Endocrinology in the period from 2013–2023. We carried out comparative and correlation analysis of hormonal (plasma cortisol concentrations after 1 mg dexamethasone (1-mg DST), urinary free cortisol (СКМ), ACTH), biochemical (glycated hemoglobin), radiological data (nodular tissue volume), course of comorbidities (metabolic syndrome, DM, AH, osteoporosis) in three groups of patients: with overt CS, mild autonomous cortisol excess (MACE) and comorbid diseases, and patients with PBMAH without hormonal activity.

RESULTS: Among 110 patients 79.1% were women, median age — 60 [51; 68]. The proportion of hormonally inactive forms of PBMAH was 37.3%, the overt CS and MACE was detected in 25.4 and 37.3% consequently. According to the hormonal ­examination data: the cortisol level during 1-mg DST was 173.8 nmol/l [86.0; 441.0], ACTH — 3.35 pg/ml [1.00; 8.00], СКМ — 445.5 [249.0; 900.0]. Statistically significant positive moderate correlations were found between the volume of nodular tissue and the level of cortisol after PDT1 (r=0.40, p<0.001), СКМ (r=0.29, p<0.004), as well as a negative moderate correlation between the volume and the level of ACTH (r=-0.40, p<0.001). When analyzing the prevalence and clinical severity of comorbid conditions, DM was diagnosed in 22 (53.7%), AH in 36 (87.8%), obesity and osteoporosis — 23 (56%) and 3 (7.3%) patients. There was no statistically significant difference in the prevalence of CS-associated diseases among the above groups (p=0.56).

CONCLUSION: PBMAH is a heterogeneous pathology with different clinical, hormonal, and imaging characteristics. A correlation was found between the volume of nodular tissue and the degree of hormonal activity of PBMAH. The obtained results emphasize the difficulty in determining clear indications for surgical treatment in the group of patients with MACE. The radicality of proposed surgical procedure should be weighed against its potential complications.

Overweight and obesity are a worldwide common problem and are diagnosed with a body mass index (BMI) value in the range of 25.0–29.9 kg/m² and ≥30.0 kg/m², respectively. Obese patients are at high risk of developing concomitant diseases, such as hypertension, type 2 diabetes mellitus (DM2), hyperlipidemia, stroke and even some types of cancer. In the Russian Federation in 2016, the proportion of overweight people was 62.0%, with obesity — 26.2%. The authors performed an electronic search in the PubMed information database. Two search elements were used: «Semaglutide» and «Obesity». The search included studies published from the date of foundation of the database to August 2022. The search was limited only to the results of clinical trials. The authors obtained 26 results, but only the studies of SUSTAIN, PIONEER (Peptide Innovation for Early Diabetes Treatment) and STEP were considered, since they were original, randomized, controlled clinical trials conducted before the approval of semaglutide for the treatment of DM2 and obesity.

The article presents a clinical observation of a patient with congenital adrenal dysfunction (CHD), a salt-losing form of 21-hydroxylase enzyme deficiency (homozygous mutation I 172N), and also with morbid obesity, due to long-term use of high doses of glucocorticosteroids, who underwent bariatric surgery — laparoscopic sleeve resection of the stomach. A feature of the presented case is the elimination of one of the causes of decompensation of the disease, namely, overweight, as well as insulin resistance, which requires the intake of large doses of glucocorticoids, which in turn leads to a worsening of the course of obesity, thereby causing a vicious circle. 7 months after surgical treatment, the goal was achieved — a reduction in the dose of Prednisolone by 25%, with a decrease in body weight by 72.1% of overweight.

The presented case clearly demonstrates the possibility of performing bariatric surgery for the treatment of morbid obesity in patients with CAH with the participation and control of a specialized multidisciplinary team. If there are indications for bariatric intervention, VDKN should not be an absolute contraindication to such operations, and the ratio of the safety profile and the efficacy profile testifies in favor of the need for their implementation.

BACKGROUND: Estrogenic deficiency is the basic condition of human ageing that leads to hypergonadotropic hypogonadism. The existence of correlation between hypergonadotropic hypogonadism, replicative (leukocyte telomere length) and biochemical data is widely supposed among females with physiological (menopausal) and pathological (primary ovarian insufficiency) estrogenic deficiency is not unreasonable.

AIM: To evaluate features of replicative (telomere length) and biochemical (metabolic syndrome) ageing markers among females with physiological (menopausal) and pathological (primary ovarian insufficiency) estrogenic deficiency.

MATERIALS AND METHODS: Research has been provided in collaboration between Endocrinology Research Centre of the Russian Ministry of Health and Lomonosov Moscow State University Medical Research and Educational Centre in the period since 10.01.2021 until 01.08.2022.

110 females (20-75y.o.) have participated in the present research.

Group 1: 26 females receiving menopausal hormonal therapy (MHT) ≥ 5 years with 0,5; 1; 2 mg estrogenic component.

Group 2: 27 females in physiological menopause without MHT

Group 3: 33 females with primary ovarian insufficiency and receiving sex-steroid replacement therapy.

Group 4: 24 healthy reproductive age females without sex-steroid replacement therapy.

Patients have undergone laboratory genetic (leucocyte telomere length), biochemical analyses.

DNA extraction — with Qiagen DNA blood mini kit (Germany). Biological material was cito conserved with Ficoll solution. Leukocyte telomere length — with real-time polymerase chain reaction PCR (Flow-fish).

Soft program IBM SPSS Statistics (version 26,0 for Windows) has been used for statical analysis.

RESULTS.

1.Menopausal females receiving MHT were inclined to highest HDL-P levels (p<0,006).

2.Females with primary ovarian insufficiency were inclined to relatively highest serum creatinine level (p<0,001).

3.Reproductive age females had relatively highest telomere length (p<0,001).

4.FSH level correlates negatively and moderately (ρ= - 0,434) leukocyte telomere length (р<0,001) among females.

CONCLUSION: Females with premature ovarian insufficiency are most sensible to ageing due to features of replicative and biochemical markers.

The article discusses various pathophysiological conditions and processes that lead to the development of tumors in diabetes mellitus. These include obesity, hyperglycemia, hyperinsulinemia, inflammation, and oxidative stress. The data of epidemiological studies are given, in which it was found that diabetes mellitus (both type 1 and type 2) increases the risk of developing the female reproductive system tumors, such as ovarian cancer, endometrial cancer, while for cervical cancer, vaginal cancer and vulvar cancer, such a relationship has not been clearly identified.

In 2023 it would have been 100 years since the birth of a prominent Soviet endocrinologist, Honored Scientist of the RSFSR, chief endocrinologist of the USSR Ministry of Defense (1962-1982), head of the Department of Therapy No. 1 for the improvement of doctors of the Military Medical Academy. CM. Kirov (1972-1982), Professor and Major General of the Medical Service Dorofei Yakovlevich Shurygin.