Gynecological endocrinology (also known as endocrine gynecology) is the unique integrative area of reproductive medicine. It was established circa 50 years ago due to breakthrough discoveries in the gynecology, endocrinology and internal medicine. According to Russian legislation there is no such specialization as endocrinologist-gynecologist but there is a lack of appropriate doctors due to complicated residenture post-diploma system in Russian national healthcare. Nowadays 80% gynecological disorders are related to endocrinopathies in opposite to 20% caused by sexually transmitted infections and orphan diseases. The aim of the present article is to present modern condition of female healthcare and actuality of endocrine gynecology service development in the Endocrinology Research Centre (Moscow, Russia).

The article is dedicated to the 100^th anniversary of the National Research Centre for Endocrinology of the Russian Ministry of Health.

AIM. To study the role of iodine, selenium and zinc in the pathogenesis of iodine deficiency and autoimmune thyroid diseases and scientifically substantiate the choice of security biomarkers and analytical methods for determination.

MATERIALS AND METHODS. Serum iodine (I), selenium (Se), and zinc (Zn) concentrations were measured using inductively coupled plasma ionization tandem mass spectrometry (Agilent 8900 ICP-MS Triple Quad); by chemiluminescent immunoassay on an automatic analyzer Architect i2000 — TSH and AT-TPO in blood serum; by enzyme immunoassay — ZnT8A; biochemical method — ALP, SOD1 in 1150 people aged from 18 to 65 years (the average age of the subjects was 40±5 years). Ultrasound of the thyroid gland was performed in the supine position using a portable ultrasound machine LOGIQe with a multifrequency linear sensor 10–15 MHz; during the study, the volume of the thyroid gland, the presence of nodules and their characteristics according to the TIRADS classification, the structure of the thyroid gland and its echogenicity were assessed.

RESULTS. In our study, the median serum iodine concentration was 60.68 μg/L (n=1150), with no significant difference between sexes. In 2%, the level of iodine in the blood serum was less than 30 mcg/l. Among the samples obtained (n=57), 19% were found to have a reduced iodine content in the lipophilic fraction — less than 10% of the total. In these samples, additional studies were performed on TSH, total and free T3 and T4 fractions. As a result, all indicators fell within the normal range, which indicates that there was no effect on thyroid function from a decrease in iodine content in the lipophilic fraction. In a comparative analysis of our previously obtained results of determining iodine in urine using the cerium-arsenite method and the inductively coupled plasma mass spectrometry method, it was found that both methods are generally comparable. The median selenium concentration was 83.38 µg/l, which corresponds to the reference values. The proportion of individuals with serum selenium levels less than 40 μg/L was 2.2%. A comparative analysis of groups of patients with serum selenium concentrations of less than 100 µg/l and more than 100 µg/l was carried out; in the group with low-normal selenium levels, the incidence of autoimmune thyroid pathology is 5% higher than in the comparison group. 60.3% of the adult population had zinc levels less than 1000 μg/L. The median serum zinc concentration was 632.9 μg/L. In regions with zinc deficiency, the incidence of autoimmune diseases (AI) of the thyroid gland and nodular / multinodular goiter is on average 10% higher than in regions with optimal zinc supply. There was no relationship between the content of zinc in the blood serum and antibodies to the zinc transporter (ZnT8A), alkaline phosphatase (ALP) and superoxide dismutase (SOD1), including in comparison of the data obtained in carriers of AT-TPO and in the comparison group (among carriers of AT-TPO: the median concentration of zinc was 644.4 μg/l, SOD1 — 117.2 ng/ml, ALP — 70.3 U/l, antibodies to ZnT8A — 249.8; in the comparison group — median zinc concentration — 744.6 μg/l, SOD1 — 102.4 ng/ml, ALP — 66.1 U/l, antibodies to ZnT8A — 242).

Thus, based on the data obtained, the relationship between thyroid pathology and micronutrient deficiencies was confirmed. No convincing evidence has been obtained on the study of additional diagnostic markers of Zn deficiency, which casts doubt on the advisability of their determination in routine practice. The ICP-MS method made it possible to propose its own reference values for I, Se, Zn and is comparable to the cerium-arsenite method in sensitivity and specificity when studying I in urine. However, due to technical features and limitations in sample size, the study population requires further improvement.

Topical diagnosis can be severely complicated in patients with primary hyperparathyroidism (PHPT) due to the ectopic placement of parathyroid gland (PTG) formations. We report a clinical case of PHPT in an 84-year-old patient caused by ectopic PTG adenoma located behind the right internal jugular vein at the level of the right submandibular gland. The impossibility of surgery for a long time due to the absence of a topical diagnosis has necessitated conservative treatment was required to get the hypercalcemia under control. In view of the concomitant deficiency of vitamin D, an attempt was made to use therapy with saturating doses of cholecalciferol under dynamic monitoring of the indicators of phosphorus-calcium metabolism, which allowed to achieve a significant decrease in PTH levels while maintaining normocalcemia.

Congenital adrenal hyperplasia (CAH) is a defect in one of the enzymes or transport proteins involved in the synthesis of cortisol in the adrenal cortex. Virile form of CAH characterized by cortisol deficiency and hyperandrogenism. Klinefelter syndrome is one of the most frequent chromosomal diseases leading to the development of primary hypogonadism. The manifestation of these two diseases could cause difficulties in diagnosis and medical treatment that lead to adverse consequences and affect the quality of life.

A 43-years-old patient consulted a physician complaining about the lack of erections for 4 years, breast enlargement. At the age of 3 years based on experienced growth of pubic hair, decreased level of 17-ketosteroids in the urine and genetic analysis diagnosis of CAH, virile form was suspected. Prednisone 5 mg daily was prescribed. At the age of 5, based on phenotypic features and karyotyping Klinefelter Syndrome (XXY) was diagnosed. At the age of 13, stimulating hormonal chorionic gonadotropin drug with only one course of 10 injections was prescribed. At the age of 18, the patient independently canceled the use of prednisone. Further, he did not receive medication therapy for CAH and Klinefelter syndrome. At the age of 42, adrenal CT revealed formation of the left adrenal gland. According to the results of the hormonal activity examination, high levels of aldosterone and renin were detected. A diagnosis of left adrenal aldosteroma was made and a left-sided adrenalectomy was performed. Histological examination diagnosis of aldosteroma did not confirmed. On physical examination, BMI 30 kg/m², genoid type of obesity, right testicle isn`t palpated, left testicle is dense, reduced in size. Small penis size. Decreased level of total testosterone, normal level of SHBG, LH and FSH was revealed. Ultrasound of the scrotum organs revealed decrease in the size of the testicles and appendages, a volumetric formation of the right testicle. Thus, diagnosis of CAH, virile form and Klinefelter syndrome, primary hypogonadism, right-sided cryptorchidism was confirmed. Hydrocortisone 30 mg daily was prescribed. Hormone replacement therapy with testosterone preparations was not prescribed until surgical treatment of neoplasm of the right testicle will be performed. On the example of this clinical case, we have demonstrate a combination of two endocrine pathologies and serious mistakes were made in the management of this patient. The management of such patients requires a multidisciplinary approach, which will avoid mistakes and improve the prognosis and quality of life of these patients.

BACKGROUND: Obesity generally determines the metabolic basis for the development of type 2 diabetes. Therefore the analysis of glycemic variability in obese individuals, especially in its different phenotypes, acquires particular relevance.

AIM: To investigate the features of glycemic variability in men with different adipose tissue distribution topography within usual dietary conditions.

MATERIALS AND METHODS: The study enrolled 43 men aged 25-65 years. Group 1 (n=17) represented obese men with subcutaneous fat distribution (SFD) while group 2 (n=16) consisted of obese men with abdominal fat distribution (AFD) and group 3 (comparator) included 10 male subjects with normal body weight (NBW). A 2-day continuous glucose monitoring (CGM) under condition of usual diet, work and physical activity was performed in each study subject. A number of parameters, indices and ratios had been assessed describing glycemic variability (GV) for daytime (6.00–23.59) and night (0.00–5.59) hours.

RESULTS: Comparative analysis of key parameters and indices describing daytime and night GV in NBW and obese men without fat distribution adjustment did not reveal statistically significant differences. After fat distribution adjustment  significantly higher mean glucose levels, standard deviation of glycemic levels and coefficient of variation were found in AFD group; also statistically significant differences were revealed in CONGA index and J-index. An analysis of the LBGI and HBGI indices that are respectively reflecting the risks of hypo- and hyperglycemia showed that the LBGI index was higher in obese men with SFD while the НBGI index was higher in men with AFD. A comparative analysis of GV parameters showed that daytime indicators values were significantly higher relative to nighttime. However the ambiguous changes in the mean glucose levels was found between study groups. Specifically in NBW men daytime and nighttime glycemia didn’t differ, whereas in AFD group there was a trend to decrease in night glucose levels (p = 0.08) while in men with SFD night decrease in glycemia became statistically significant (p=0.005).

CONCLUSION: Results of glycemic variability assessment in obese men suggest that abdominal and subcutaneous types of fat distribution are associated with specific features of carbohydrate metabolism and determine different risk levels for developing type 2 diabetes in patients with AFD and SFD.

BACKGROUND: Self-monitoring of blood glucose (SMBG) is the main tool to achieve carbohydrate metabolism targets in patients with type 1 diabetes mellitus (DM). Remote monitoring of SMBG in Russia appeared relatively recently and needs to be evaluated for effectiveness.

AIM: To evaluate the effect of remote monitoring of SMBG on carbohydrate metabolism and quality of life in patients with type 1 DM in order to form new therapeutic approaches.

MATERIALS AND METHODS: Patients with type 1 DM with glycated hemoglobin (HbA1c) from 8.0 to 12.0% were divided into the main (n=107) and control group (n=20). Patients from the main group performed SMBG using glucometers with the possibility of remote data transmission, patients from the control group continued the traditional SMBG. The dynamics of HbA1c, derived time spent in the target ranges, recognition of hypoglycemia (GOLD scale, Clarke questionnaire), quality of life according to the SF-36 questionnaire were evaluated. The statistical analysis was carried out in the SPSS Version 26.0 program (IBM, USA).

RESULTS: In the main group (n=88) the HbA1c was statistically significant decreased after 6 months from 9.0% [8.4; 9.9] to 8.1% [7.4; 9.2] (p<0.001), with SMBG more than 4 times a day - up to 7.3% [7.0; 7.8] (p=0.001). In the control group (n=20), by the 6th month, HbA1c increased to 10.1% [8,9; 11,2] (p=0,010). Derived Time In Range in the main group increased to 69.9±13.0 (95% CI 65.73–74.03; p<0.001); derived Time Above Range significantly decreased to 9.5% [6.4; 15.0] (p<0.001), derived Time Below Range — to 6.7% [2.8; 12.2] (p=0.044); Coefficient of Variation reached 36.3±7.9 (95% CI 33.7–38.8; p<0.001). According to the results of SF-36, the physical and psychological components of the quality of life in the main group significantly improved (p<0.001). Recognition of hypoglycemia improved in the intervention group (-4.5% of patients (p=0.046) according to the Clarke questionnaire; -8% (p=0.008) on the GOLD scale).

CONCLUSION: Remote monitoring of SMBG is a prospective therapeutic approach due to its positive effect on carbohydrate metabolism and quality of life in patients with type 1 DM.

In a review of the generalized results of foreign and domestic studies on the development mechanism and pathogenesis of vascular calcification. The etiopathogenetic, pathophysiological and histomorphological features of mediacalcinosis, which reveal changes in the vascular bed in patients with DM, are considered. The role of risk factors for diseases, such as increased glycemia, changes in insulin levels, impaired lipid metabolism, obesity, arterial hypertension, CKD and aging, is indicated. The role of procalcifying and anticalcifying factors in colonic vascular remodeling is discussed. Identification of informative molecular markers and factors of CS will allow in the future to develop effective strategies for drug management of the risk of their progression and individual prevention programs to improve the quality and life expectancy in patients with cardiovascular diseases.

Disorders of sex development (DSD) represent a group of congenital conditions in which there is a discrepancy between the chromosomal and (or) gonadal sex and the structure of the genitals. Within the DSD there is a subgroup of 46,XX testicular DSD (46,XX TDSD), which may be caused by the translocation of the SRY gene, and more rarely — due to other causes (SRY-negative forms). In this report, we present an observation of a patient with SRY-negative 46,XX TDSD, in whom the condition was initially regarded as a virile form of congenital adrenal hyperplasia, then as idiopathic intrauterine virilization in a girl. Due to the development of virilization at the age of 11, the presence of testicular tissue was suspected. Molecular genetic analysis (whole exome sequencing with Sanger validation) revealed a de novo variant in exon 9 of the WT1 gene (chr11:32413528T>C), which, according to predictions, did not lead to a change in the amino acid sequence (p.Thr479=, NM_024426.6), but disrupted splicing, resulting in a previously described in 46,XX TDSD a change in the C-terminal domain of WT1. After verification of the diagnosis, a gonadectomy was performed and estrogen replacement therapy was prescribed. Thus, we have described a patient with a rare form of 46,XX TDSD caused by a variant in the WT1 gene. The presented observation illustrates the difficulties of differential diagnosis of intrauterine virilization syndrome in female karyotype.

This article describes the first experience of successful use of growth hormone (GH) in combination with an aromatase inhibitor (AI), in a 14-year-old boy. At the age of 7, he presented with headaches, nausea and vomiting, and MRI revealed a craniopharyngioma (CP). An Ommaya system was implanted, and radiation therapy was performed. As a result of treatment, GH deficiency and secondary hypothyroidism developed. At age 9 years, signs of puberty appeared. Growth rate remained satisfactory until the age of 14 years. At the age of 14 growth rate slowed down, which was the reason for appointment. Upon examination, the bone age was 16 years and the projected final height without therapy was 162 cm. Given the poor growth prognosis, IA anastrozole in combination with GH was prescribed. During two years of therapy the growth gain amounted to 12.5 cm. This observation demonstrates that normal growth rates in patients with CP do not indicate preserved somatotropic function of the pituitary gland. With preserved sexual function, early or premature puberty may be observed. In such cases, IA can be prescribed in addition to GH — these are medications that inhibit the closure of growth. GH therapy in combination with IA is highly effective and safe in patients with GH deficiency after treatment of KF during puberty and allows to achieve good growth parameters.

Differentiated thyroid carcinoma (DTC) is the most common endocrine cancer, accounting for 90–95% of thyroid malignancy and predominant in the female population of all age groups. Surgery is the standard primary treatment for patients with DTC, followed by radioactive iodine therapy (RAIT) when indicated. After the main treatment, patients receive thyroid hormone therapy in a variety of regimens, either as a replacement therapy or as a therapy intended to suppress secretion of thyroid-stimulating hormone (TSH).

The impact of RAIT on the health of individuals with DTC has been studied for years. The accumulation of ¹³¹I in organs and tissues, as well as some organs’ direct involvement in the metabolism of ¹³¹I-containing substances and its excretion, can lead to secondary complications. Reproductive health in the context of RAIT has also been a popular research topic because DTC is frequently found in young individuals.

We may identify a direction for future study in this field and the requirement for adjustments in patient management thanks to the data summarized in this review on the effect of RAIT for DTC on female reproductive health.

BACKGROUND. Functional hypothalamic amenorrhea (FHA) and polycystic ovary syndrome (PCOS) are pathologies most common in women of reproductive age. Menstrual irregularities (oligo/amenorrhea) are the most common symptom of these diseases. FHA develops against the background of stress or excessive physical exertion, and is characterized by inhibition of neuroendocrine regulation of the hypothalamic-pituitary-ovarian axis with a subsequent decrease in the production of sex steroids. For PCOS, the most important pathogenetic links are insulin resistance and hyperandrogenism. The pathology of neuroendocrine regulation in ovarian hyperandrogenism is accompanied by excessive pulsatile secretion of gonadotropin-releasing hormone (GnRH), promoting increased production of luteinizing hormone (LH). Both FHA and PCOS lead to multiple complications from other organs and systems: cardiovascular pathology, decreased bone mineral density with prolonged amenorrhea and contribute to the development of infertility.

OBJECTIVE. To analyze the works studying the problems of differential diagnosis of FHA and PCOS.

METHODS. Using PubMed, eLibrary, CyberLeninka.ru, a systematic search was conducted for articles published over the past 6 years that met the following criteria: the research that describe methods and develop criteria for the differential diagnosis of FHA and PCOS. Selected impactive publications within 1998–2018 were also included in the review.

RESULTS. This review highlights the differential diagnostic criteria for FHA and PCOS. The features of clinical, laboratory and instrumental studies are also described. Publications describing the coexistence of these pathologies in women are analyzed, and methods that allow differentiating these nosologies are described in detail.

CONCLUSION. A correct and timely diagnosis facilitates the prescription of appropriate treatment regimens, reduces the incidence of complications and improves the quality of life of women. In light of recent advances in the description of the mechanisms of neuroendocrine regulation of the reproductive system, it is necessary to further conduct research to study the role of neuropeptides in the development of FHA and PCOS, which may serve to create more accurate diagnostic markers of diseases.

On September 27, 2024, a discussion-based working meeting on the issue of vitamin D deficiency in patients with overweight and obesity was held in Vladikavkaz.The meeting aimed to evaluate the relationship between vitamin D deficiency, overweight, and associated comorbidities, as well as to explore modern strategies and practical approaches for managing such patients in endocrinology practice. The resolution of the meeting was developed by its participants, comprising leading endocrinologists.