Problemy endokrinologii最新文献

Congenital hypogonadotropic hypogonadism (СНH) is a group of diseases caused by impaired synthesis or secretion of gonadotropin-releasing hormone (GnRH) and gonadotropin hormones. At present, more than twenty genes involved in the development of СНН have been described. In the structure of HGH, the most common forms of the disease are caused by pathogenic variants in genes involved in the ontogenesis, migration and survival of GnRH neurons, whereas pathology of genes involved in the action/transmission of GnRH signals in normally developed GnRH neurons is less common. This article describes a rare variant of СНН as a result of pathogenic variants in the POLR3B gene, occurring in 1.1% of cases of СНН, which is a component of hypomyelinating leukodystrophy 4H and includes hypomyelination, CHН, hypodontia. Identification of the genetic nature of the disease in this patient made it possible not only to establish the cause of CНН, but also to diagnose comorbid conditions.

The basis of the vital activity of each cell of the body is energy metabolism, necessary for the implementation of physiological needs in norm and pathology. The most important pathways for the synthesis of adenosine triphosphate are glycolysis, the tricarboxylic acid cycle and oxidative phosphorylation. Glucose, free fatty acids and amino acids can be used as a substrate for obtaining energy. As the disease develops, reprogramming occurs in cells with the ability to switch between energy pathways and the choice of its sources, forming a specific metabolic phenotype that ensures cell survival and the formation of clinical characteristics of the disease. The availability of information on pathophysiological changes at the level of cell metabolism is of scientific and practical interest in relation to the development of methods for accurate diagnosis and the choice of personalized tactics in each specific case. This review describes the characteristics of energy metabolism in normal and tumor cells. It also provides information on modern methods for assessing energy metabolism in the body.

Background: Recurrent hypoglycemia occurs during insulin therapy in patients with diabetes mellitus and is a significant cause of brain dysfunction in these patients. The functioning of the hematocerebrospinal fluid barrier and the production of cerebrospinal fluid (CSF) are of great importance in ensuring brain activity. The main volume of CSF is formed by the choroid plexus of the lateral ventricles (LV) of the brain and the glymphatic system of the brain. The role of the choroid plexus in the development of brain dysfunction in hypoglycemia has not been sufficiently studied.

Objective: The aim of this work was to determine the structure of the choroid plexuses of the lateral ventricles of the brain during recurrent hypoglycemia.

Materials and methods: The object of the study were rats that had undergone 9 hypoglycemic states after insulin administration (with an interval of 3 days, the blood glucose level of 1.4-1.8 mmol/L) and intact animals. The volume of the LV and volume fractions of the choroid plexuses in the LV were estimated: the relative volume and total fraction of vessels, fractions of cells and connective tissue. Morphological changes in the epithelium of the choroid plexus and nervous tissue of the periventricular spaces were also recorded.

Results: In animals that had undergone a series of hypoglycemias, the maximum cross-sectional area of the LV, the relative volume of the choroid plexuses of the LV and the volume fraction of vessels per volume of the choroid plexus of the LV increase. The volume fraction of cells per volume of the choroid plexus of the ventricles decreases in rats with recurrent hypoglycemia. Morphological examination of these animals reveals dystrophic changes in the epithelial cells of the choroid plexus and zones of dystrophic changes in the brain tissue surrounding the ventricles.

Conclusion: Thus, recurrent hypoglycemia leads to an increase in the maximum cross-sectional area of the LV and the relative volume of the choroid plexuses, as well as dystrophic changes in the epithelial cells of the choroid plexuses and neurons of the periventricular spaces. Since hypoglycemia is repeatedly observed during the treatment of patients with diabetes mellitus, the identified changes may cause cognitive impairment and the development of dementia in these patients.

Menopausal symptoms can disrupt the lives of women at the peak of their careers and family life. Currently, the most effective treatment for these symptoms is menopausal hormone therapy (MHT). The presence of cardiovascular and metabolic diseases does not preclude the use of MHT to relieve menopausal symptoms and improve quality of life. However, physicians' concerns about causing more harm than good often hinder the use of this type of hormone therapy. Caution is especially important when it comes to women with comorbidities. Moreover, it should be acknowledged that high-quality studies on the safety of MHT for major chronic noncommunicable diseases and common comorbid conditions are insufficient. This consensus document analyzes all currently available data from clinical trials of various designs and develops a set of eligibility criteria for prescribing MHT to women with comorbid cardiovascular and metabolic diseases. Based on this document, physicians of various specialties who consult with women in menopause will receive an accessible algorithm that will allow them to avoid potentially dangerous situations and appropriately prescribe HRT in clinical practice.

Von Hippel-Lindau syndrome (FHL) is a rare autosomal dominant disease that leads to the formation of multiple organ tumor syndrome. The pathology is primarily caused by the inactivation of the VHL gene, which is located on chromosome 3 (3p25/26) and encodes ubiquitin ligase, which destroys hypoxia-induced factor-1α (HIF-1α). The genetic defect leads to the accumulation of HIF-1a protein, activating key carcinogenic pathways, and activated cytokines cause abnormal proliferation of tumor cells and oncogenesis. To date, more than 500 mutations have been registered in VHL. FHL syndrome is characterized by various tumors, including hemangioblastomas of the retina and central nervous system, pheochromocytomas, clear cell renal cell carcinoma, cystic adenoma and others. In the presented clinical description, pheochromocytoma was initially diagnosed in the patient's mother, and 2 months later in the eldest son. Subsequently, the results of a molecular genetic study made it possible to verify the diagnosis, since in the gene in exon 3 of VHL, a single nucleotide was replaced in the heterozygous state of C.500 G>A, leading to the replacement of the amino acid p.R167Q. Identification of the VHL gene mutation required genetic counseling of all family members, during which a similar mutation was identified in the younger brother. Surgical treatment is the main method of treating FHL syndrome, but advances in genetic research technologies provide new opportunities for the treatment of tumors associated with this syndrome.

Background: Currently, alternative minimally invasive methods for assessing the steroid profile in patients with congenital adrenal hyperplasia (CAH) are being actively developed. Saliva has proven to be a promising medium in a series of international studies. The use of saliva as an alternative minimally invasive biological material not only reduces the stress associated with venipuncture but also decreases the workload for medical staff, as saliva collection can be performed at home.

Aim: Evaluate the correlation between concentrations of steroid hormones in the blood and saliva in prepubertal and pubertal groups of patients with congenital adrenal hyperplasia using high-performance liquid chromatography with tandem mass spectrometric detection (HPLC-MS/MS).

Materials and methods: A prospective intervention study for diagnosing and disease compensation in 45 patients aged 3 to 17 years undergoing a routine inpatient examination with an established diagnosis of CAH (classic 21-hydroxylase deficiency). All children underwent a one-stage laboratory test at the National Medical Research Center of Endocrinology of the Ministry of Health of the Russian Federation in October 2024.

Results: In the prepubertal group (N=14), a strong positive correlation was found between serum and saliva for the concentration of 17OH-progesterone (p=<0.01; r=0.88), androstenedione (p=<0.001; r=0.84) and dehydroepiandrosterone (p=0.001; r=0.78). In the pubertal group (N=31), a strong positive correlation was found between serum and saliva for the concentrations of 17OH-progesterone (p=<0.01; r=0.94), androstenedione (p=<0.01; r=0.94), testosterone (p=<0.01; r=0.94), and progesterone (p=<0.01; r=0.79), as well as a moderate correlation for 21-deoxycortisol (p=0.003; r=0.52).

Conclusion: Most steroids used for diagnosis and monitoring the therapy in patients with CAH have a strong or moderate correlation between serum and saliva.

Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder associated with a lifelong increased risk of tumor development. Comprehensive monitoring of patients with NF1, involving a multidisciplinary team of specialists and the implementation of screening programs, is crucial for the early detection of associated pathological conditions that contribute to disability and reduced life expectancy. This article presents a clinical case of an adolescent female patient with tumor manifestations of NF1, in whom both diagnosed neoplasms - plexiform neurofibroma and pheochromocytoma, had a symptomatic course, significantly affecting her physical health and quality of life. A multidisciplinary approach and correct treatment led to favorable outcomes, enabling the patient to resume a normal lifestyle, despite the continuation of targeted therapy.

Background: Secondary amenorrhea is a pathological condition that may develop as a result of either functional hypothalamic amenorrhea (FHA) or primary ovarian insufficiency (POI). In recent years, metabolomic studies in gynecology have gained importance for improving diagnostics, optimizing pharmacological treatment, and monitoring therapeutic outcomes. It is well established that cortisol production increases in response to chronic stress and relative energy deficiency syndrome. Therefore, it is reasonable to expect elevated cortisol levels in patients with functional amenorrhea associated with weight loss, which may adversely affect menstrual function.

Objective: To investigate and compare the parameters of the multicomponent blood steroid profile (multisteroid analysis), including androstenedione, corticosterone, testosterone, cortisol, cortisone, and dehydroepiandrosterone (DHEA), in patients with secondary amenorrhea of different origins (FHA, POI), and to identify alterations in target markers using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS).

Materials and methods: A single-center cross-sectional comparative study was conducted involving two populations of women aged 18-39 years: (1) patients with secondary amenorrhea of various origins (FHA, POI) (n=120), and (2) healthy women (n=34). Blood steroid profile parameters were assessed using HPLC-MS/MS.

Results: A total of 154 women were examined. The lowest corticosterone levels were observed in the POI group - 3.95 nmol/L [2.4; 5.7] (p<0.0001). No statistically significant differences were found between other groups. Hypercortisolemia was not detected in any of the study participants, nor were there significant differences in cortisol, cortisone, or DHEA levels between groups.

Conclusion: In this study, based on a targeted quantitative analysis of steroid hormones, their precursors, and metabolites using HPLC-MS/MS technology, we characterized the features of the blood steroid profile in patients with secondary amenorrhea. The profile demonstrated similar characteristics across all amenorrhea types, regardless of etiology, suggesting a common underlying mechanism. However, the observed decrease in corticosterone levels in POI patients and the absence of hypercortisolemia in FHA women are of particular interest and warrant further investigation.

Introduction: Among the disorders of sex development (DSD) with karyotype 46,XY, there is a group of diseases caused by defects of androgen synthesis. The last stage of in the synthesis of androgens is the conversion of testosterone into a more active androgen dihydrotestosterone, which occurs under the influence of the enzyme 5α-reductase type II (SRD5A2). SRD5A2 deficiency is a rare disease with autosomal recessive inheritance.

Aim: To give a clinical and molecular genetic characterization of 14 new cases with confirmed molecular diagnosis of SRD5A2 deficiency, as well as 4 cases of DSD 46,XY, where monoallelic changes in the SRD5A2 gene were detected.

Materials and methods: The study included 310 patients with DSD 46,XY. Molecular genetic analysis was performed using the NGS method using a targeted panel for multiplex amplification and subsequent sequencing of the coding regions of the following genes: AKR1C2, AKR1C4, AMH, AMHR2, AR, ARX, ATRX, CBX2, CYB5A, CYP11A1, CYP17A1, DHCR7, DHH, EMX2, ESR2, FGD1, FGF9, FGFR2, FKBP4, FOXF2, FOXL2, HOXA13, HSD17B3, HSD3B2, ICK, LHCGR, LHX1, LHX9, MAMLD1, MAP3K1, MID1, NR0B1, NR5A1, POR, PTGDS, SOX9, SRD5A2, SRY, STAR, SUPT3H, TSPYL1, WNT4, WT1, ZFPM2.

Results: By molecular genetic analysis 16 different variants were identified in the SRD5A2 gene (2 in several families), 4 of which had not been previously described.

Conclusion: The study highlights the importance of molecular genetic analysis in the differential diagnosis of DSD 46,XY.

On June 26, 2025, a meeting of the expert working group was held in Moscow. The discussion focused on the personalized approach of tirzepatide («Tirzetta®») and semaglutide («Velgia Eco®») in patients with excess body weight, obesity, and type 2 diabetes. Following the meeting, the objective was set to develop a consensus-based algorithm for prescribing these drugs to ensure their effective use in Russian clinical practice.