Pharmateca

Ожирение является не только эстетической проблемой, но также ведет к ухудшению прогноза в отношении продолжительности жизни. Появляются инновационные стратегии, позволяющие контролировать вес, а значит, улучшать качество и повышать продолжительность жизни пациента. Этой теме был посвящен симпозиум «Технологии будущего для управления здоровьем сегодня», который прошел при поддержке компании «Промомед» 29 марта 2025 г. в рамках XXI Московского городского съезда эндокринологов «Эндокринология столицы – 2025».

Background. Currently, the criteria for vitamin D deficiency, as well as the recommended doses for its intake, remain controversial. The variety of recommendations for the intake of cholecalciferol are associated with different purposes of use: obtaining a sufficient daily intake, preventing rickets and osteomalacia, reducing the risk of fractures, or reducing cardiovascular risks and mortality. There are also controversial issues regarding the classification of vitamin D status and the terminology associated with the serum 25(OH)D concentration. The current classification of vitamin D status does not take into account changes in individual sensitivity to the action of vitamin D, which may be attributable to genetic, epigenetic, nutritional factors, concomitant diseases, or medications. Despite the active study and implementation of D-deficiency prevention, the prevalence of vitamin D deficiency remains high in the Russian Federation, including in young people.

Objective. Evaluation of the dynamics of the blood serum 25(OH)D level in young people without chronic and acute diseases aged 18 to 35 years while taking cholecalciferol preparations.

Materials and methods: 84 people aged 18 to 35 years were examined, including 49 (58.3%) men and 35 (41.7%) women with vitamin D deficiency. All participants with vitamin D deficiency were recommended cholecalciferol at a dose of 5000–7000 IU/day, depending on the level of D-deficiency for 3 months to replenish (“saturate”) the deficiency. Determination of blood serum 25(OH)D level was performed by the immunochemical analysis method upon inclusion in the study, and then after 3 and 6 months (if necessary) while taking cholecalciferol. The study was conducted from 03/09/2023 to 05/06/2024.

Results. After 3 months of «saturation therapy», 75% of participants (63 of 84) achieved the target blood level of vitamin D (≥30 ng/ml), including 38 (77.55%) men and 23 (65.71%) women. After 6 months of treatment, 68 (80.96%) participants achieved the target blood level of vitamin D (≥30 ng/ml, including 43 (87.76%) men and 25 (71.43%) women. Replenishment of vitamin D deficiency with saturating doses of cholecalciferol was generally effective. In men, the dynamics of D-deficiency treatment was more favorable than in women: the average blood vitamin D level increased from 13.13 to 35.33 ng/ml, an increase of 257%; in women, the average blood vitamin D level increased from 5.45 to 32.16 ng/ml, an increase of 122%. Student’s t-test for independent samples showed that the differences in the dynamics of vitamin D deficiency treatment between men and women are statistically significant (t=2.62; p=0.01). However, not all study participants achieved the adopted target levels, which suggests that an individual approach with the selection of the dose and duration of «saturation therapy» will be required.

Conclusion. In general, loading doses of cholecalciferol in most people contribute to the restoration of vitamin D levels in case of its initial deficiency. However, there are those who do not achieve the adopted target values when taking saturating doses of cholecalciferol. Probably, in such cases a personalized approach with individual selection of the dose and duration of treatment taking into account various factors are required.

At the present stage, the non-infectious epidemic of diabetes mellitus (DM) has awakened the interest of researchers, specialists, and analysts of various profiles in its complications. The problems of microvascular complications are designated as medical, social, and economic. Diabetic retinopathy (DR) is one of the severe microvascular complications, the number of which at the beginning of 2023 was 706,407 thousand people. A screening study conducted in 16 regions of Russia showed that the actual number of patients with diabetes with eye complications is significantly higher than the official registry data. Many specialists are puzzled the scale of prevalence of negative outcomes of DR (disability and blindness), the complexity of pathology management. Taking into account the above, this review is devoted to the characteristics and assessment of the current state of diabetic retinopathy. Most researchers focus on the clinical and diagnostic aspects of the problem, which is quite justified. The publications describe modern methods of treatment and their effectiveness, prove the effectiveness of early diagnostics, the influence of risk factors. A number of works emphasize the negative aspects of organizational issues. Official statistics do not contain data on diabetic retinopathy, which makes it difficult to assess the level, dynamics of the forecast of epidemiological indicators necessary for taking effective measures to change the situation. This problem is solved with the help of the Federal Register of SD (FRSD). Meanwhile, the long-term work of legislators and government agencies on the development of regulatory legal acts, the creation of interdisciplinary approaches suggests the effectiveness of the steps taken.

Objective. Substantiation of the use of intelligent mobile applications for glucometers for more effective remote management of diabetes mellitus (DM) as a real alternative to continuous glycemic monitoring (CGM) for diabetic patients with DM.

Key provisions. Achieving adequate control of DM is impossible without self-monitoring by the patient. Guidelines for managing patients with DM are regularly updated, more modern approaches to self-monitoring of glycemia are developed, innovative glucometers, systems with a mobile application, are introduced. Continuous glucose monitoring systems are increasingly used. The use of CGM and FMG technologies allows for real-time glycemia control. Meta-analyses of studies evaluating the effectiveness of these technologies show advantages in increasing the percentage of time glycemia is in the target range and reducing periods of hypoglycemia, and the use of a food diary in the form of an application contributes to more effective weight loss. The use of modern mobile applications to a glucometer or CGM allows for increasing patient motivation and expanding opportunities for disease management.

Objective. Evaluation of the impact of deintensification of the basal-bolus insulin therapy (BBIT) regimen and premixed insulin therapy (PMIT) in elderly patients with type 2 diabetes mellitus (DM2) on glycemic control, hypoglycemic events, functional and cognitive status.

Methods. A prospective, observational, uncontrolled study included 44 DM2 patients (Me age 70.5 [67–75] years) on BBIT or PMIT in combination with oral hypoglycemic agents or glucagon-like peptide-1 receptor agonists (PMIT +/- OHA/GLP-1RA) who discontinued bolus insulin and continued therapy with basal insulin preparations in combination with AHA and/or GLP-1 AR. An examination according to the algorithms for providing medical care to diabetic patients and comprehensive geriatric assessment were conducted.

Results. After deintensification of insulin therapy, the insulin dose decreased from 58 U [47–75] to 31 U [22–50] (p=0.001), the HbA1c level did not change: 8.7 [7.7–10.2]% vs. 8.8 [7.9–10.1]% (p=0.542). The proportion of patients experiencing mild hypoglycemia decreased from 67.6% to 32.6% (p=0.003), the frequency of mild hypoglycemia decreased from 1 [0–4] to 0 [0–2] per 1 patient (p=0.001). BMI decreased from 31.2 kg/m² [27.55–36.75] to 30.5 kg/m² [26.25–35.65] (p=0.005). The time to complete the Stand and Go test decreased from 10.6 sec [8.5–12.0] to 8.0 sec [7.0–9.0] (p=0.02). The proportion of patients with risk of falls decreased from 54.3% to 17.1% (p=0.02). The functional and cognitive status of patients did not change.

Conclusions. Deintensification of insulin therapy by discontinuing bolus insulin in elderly patients with type 2 diabetes mellitus reduced the incidence of hypoglycemic events without worsening glycemic control, led to weight loss, and was associated with an increase in walking speed and a decrease in the risk of falls.

Background: In order to intensify therapy, hypoglycemic drugs that provide not only optimal glycemic control, but also have non-glycemic properties can be used.

Objective. Evaluation of the glycemic and non-glycemic effects of the fixed combination (FC) of insulin glargine and lixisenatide in patients with type 2 diabetes mellitus (DM2) in everyday clinical practice over 24 months of follow-up.

Materials and methods. The study included 35 DM2 patients who did not achieve compensation of carbohydrate metabolism during previous hypoglycemic therapy. Patients were prescribed the FC of insulin glargine and lixisenatide. Anthropometric data, parameters of carbohydrate metabolism and lipid spectrum, and hemodynamic parameters were analyzed initially and after 24 months. Additionally, the frequency of symptomatic hypoglycemic states and severe hypoglycemia was assessed.

Results. After 24 months of treatment with FC of insulin glargine and lixisenatide, glycemic control parameters were improved without weight gain and hypoglycemic episodes, lipid metabolism parameters with a positive effect on systolic blood pressure.

Conclusion: FC of insulin glargine and lixisenatide not only provide optimal glycemic control, but are also capable of exerting a number of pleiotropic effects in the form of weight loss, improved lipid parameters and systolic blood pressure.

Background: One of the most common causes of congenital hypopituitarism is the occurrence of inactivating variant aberrations in the PROP1 gene. Encoding the transcription factor of the same name, PROP1 is a key regulator of the differentiation of pluripotent cells of the anterior pituitary gland into individual cell lines with characteristic secretory profiles. Homozygous and compound heterozygous variants of the PROP1 gene lead to the development of combined pituitary hormone deficiency, characterized by deficiency of somatotropic hormone (STH), thyroid-stimulating hormone (TSH), prolactin (PRL), and gonadotropic hormones. Deficiency of adrenocorticotropic hormone (ACTH) is a more variable symptom, in rare cases it can develop in childhood, more often in adolescence and older age, or it can be absent throughout the patient’s life. In 1998, cDNA of the human PROP1 gene was cloned by P. Duquesnoy et al. In the same year, O.V. Fofanova, together with S. Yamashita and other Japanese scientists were among the first to identify defects in the PROP1 genes in patients with multiple pituitary hormone deficiency. More and more data concerning the study of this problem are appearing in the foreign literature. In the domestic literature, there are descriptions of a small number of groups of patients with defects in the PROP1 gene. This work is aimed at expanding the understanding of the etiology, pathogenesis and characteristics of this rare disease.

Objective. Clinical, hormonal and molecular genetic characteristics of cases of monogenic hypopituitarism associated with variants in the PROP1 gene.

Materials and methods: A single-center, non-interventional, cross-sectional, non-comparative study was conducted, which included 54 patients with hypopituitarism associated with a variant substitution in the PROP1 gene. All patients underwent a comprehensive examination, including laboratory and instrumental diagnostic methods and NGS (next-generation sequencing).

Results: 54 children (30 girls, 24 boys) with variant substitutions in the PROP1 gene were examined. The frequency of variant substitutions in the PROP1 gene among children with monogenic hypopituitarism in the Russian population was 44% (95% CI: 34.5–52.7). All identified variants in the PROP1 gene were previously described in the world literature as pathogenic. The most common defect was the compound heterozygous variant c.301_302del/c.150del – detected in 23 (42.5%) cases. The age at the time of hypopituitarism diagnosis was 4.5 (3.0–5.6) years. All children had growth hormone deficiency and secondary hypothyroidism. In a smaller number of cases, hypopituitarism included corticotropic hormone deficiency (40.7%) and hypoprolactinemia (16.6%). Secondary hypogonadism was diagnosed in all children who reached puberty (n=17). According to the results of magnetic resonance imaging of the brain, changes typical for a defect in the PROP1 gene (hyperplasia of the pituitary gland and total changes in the structure of the pituitary gland) were detected in 46% of cases, pituitary hypoplasia – in 26% of cases.

Conclusion: The largest domestic study on the frequency of PROP1-associated hypopituitarism was conducted. In patients with the same aberration, the age and sequence of manifestation of tropic deficiencies can vary significantly. The high probability of developing secondary hypocorticism in this genetic defect postulates the extreme importance of monitoring patients throughout their lives, including the need for regular monitoring of serum cortisol levels.

Background: Recently, more and more attention has been paid to the study of acute and late consequences of cancer treatment. To date, a small number of studies on thyroid dysfunction in the acute period after radiation therapy (RT) to the neck and supraclavicular lymph nodes have been published in the literature.

Objective: Assessment of the prevalence of structural and functional changes in the thyroid gland in the acute period after RT for head and neck cancer (HNC) and breast cancer (BC).

Materials and methods: The prospective study included 35 patients, median age – 46 years [41; 49]: 14 patients with HNSCC (7 men and 7 women) and 21 patients with BC. The study of the TSH, free T4, thyroglobulin levels and thyroid ultrasound were performed before the start of RT, immediately after its completion and 6 months later.

Results: In three patients (8.57%), destructive thyroiditis was detected immediately after the completion of RT – subclinical thyrotoxicosis was registered in one patient with HNSCC and in one patient with BC. Another patient with BC had a hypothyroid phase of destructive thyroiditis. In all three cases, the patients did not present any complaints, and the laboratory parameters reached the reference values during the repeat examination after 6 months. When comparing the parameters over time, a significant decrease in the thyroid gland volume was noted immediately after RT compared to the volume before RT (p=0.043). After 6 months, 2 cases of hypothyroidism (5.71%) were noted: one case of subclinical hypothyroidism after treatment for BC and one case of manifest hypothyroidism after treatment for HNC.

Conclusion: In the early period after RT, destructive thyroiditis may develop, which has no clinical manifestations and resolves spontaneously within a few months. After 6 months, the risk of hypothyroidism increases, requiring replacement therapy.

Background: Type 2 diabetes mellitus (DM2) is one of the main causes of chronic kidney disease (CKD) and end-stage renal failure. The medical community continues to debate the possible impact of intestinal microbiota (IM) imbalances on CKD progression. IM is a collection of microorganisms that play an important role in maintaining the health of the macroorganism and participate in various physiological processes. One of the urgent problems is the study of the composition of IM in patients with CKD and DM2. Most studies of IM were conducted in patients with CKD stages 4-5. This article presents the results of a study of the state of IM in diabetic patients with CKD at pre-dialysis stages in combination with chronic pyelonephritis (CP), obtained by gas chromatography-mass spectrometry (GCMS) using the microbial marker mass spectrometry (MMMS) method.

Objective. Evaluation of the composition of IM in the Moscow population of patients with DM2 in combination with CP at pre-dialysis stages of CKD by GCMS of fecal samples using the MMMS method.

Materials and methods: The IM analysis was conducted from 2021 to 2024 in 69 patients (23 patients with DM2 and CKD stages 3-4; 9 with CKD stages 3-4 with DM2 in combination with CP; 23 with DM2 and CKD stage 2; 14 with DM2 and without CKD) and 26 healthy volunteers. Results: It was found that in patients with DM2 without CKD, compared with healthy volunteers, there was a significant decrease in the number of Prevotella spp., Propionibacterium jensenii and Bacteroides fragilis, as well as a significant increase in Bacillus megaterium (Priestia megaterium) (p<0.05). In the group of patients with DM2 and stage 2 CKD, compared with patients with DM2 only, an increase in the number of Fusobacterium spp./Haemophilus spp. (p<0.05) was found. Comparison of patients with DM2 and stage 3–4 CKD with patients with DM2 and stage 2 CKD showed a decrease in Lactobacillus spp. and Ruminococcus spp. in the group of DM2 and stage 3–4 CKD. At the same time, these patients showed a significant increase in Propionibacterium acnes (Cutibacterium acnes) and Actinomyces spp. (p<0.05). In patients with DM2 and stage 3–4 CKD with exacerbation of chronic pyelonephritis who received antimicrobial therapy, a significant increase in the number of Rhodococcus spp., total microbial load, total bacterial load, anaerobes and Peptostreptococcus anaerobius 18623 was found compared to patients with DM2 and stage 3-4 CKD without CP (all p < 0.05).

Conclusion: In this study, for the first time in the Moscow population, the composition of IM in patients with DM2 at various pre-dialysis stages of CKD was studied and compared. The results obtained determine the need for further study of the role of IM and the prognostic value of its changes in the progression of CKD.

Regular physical activity is an integral part of the life of patients with type 1 diabetes mellitus (DM1) due to their young age. Regular aerobic physical activity is associated with improved overall well-being and is a method of preventing cardiovascular diseases. An increased risk of nocturnal hypoglycemia after physical activity is a factor limiting physical activity, especially in young patients and children. Insulin degludec is an analogue of long-acting basal insulin (with a duration of action of more than 42 hours), which has a low variability of action. The ADREM study, conducted using continuous glucose monitoring systems, demonstrated that afternoon aerobic exercise in patients with DM1 treated with insulin degludec did not affect the risk of subsequent nocturnal hypoglycemia. This article reviews a case series of patients with DM1 treated with insulin degludec and regularly engaged in physical activity.

Background: Timely diagnosis of pheochromocytoma (PCC) is difficult due to the rare occurrence of this pathology (1:200,000 population) and variability of clinical symptoms. One of the manifestations of PCC is arterial hypertension (AH), which can be either paroxysmal in nature or manifest as persistent AH resistant to antihypertensive therapy.

Description of the clinical case: The article considers the clinical case of an elderly patient who, despite typical complaints for FCC and therapy-resistant hypertension, was followed-up for a long time with a diagnosis of arterial hypertension (AH). This led to uncontrolled hypertension and the development of acute cerebrovascular accident (ACVA). For the first time, the diagnosis of FCC was suspected during the treatment of COVID-19 after chest multispiral computed tomography (chest MSCT) and the detection of a formation in the left adrenal gland. Surgical removal of FCC led to normalization of blood pressure (BP) in the postoperative period without taking any antihypertensive drugs.

Conclusion: The presented clinical case shows the importance of the earliest possible diagnosis of FCC in patients with therapy-resistant hypertension in order to avoid the development of serious complications, including ACVA. The article summarizes the current recommendations for the diagnosis of pheochromocytoma, which suggest the determination of blood or urine methylated catecholamine levels (metanephrine, normetanephrine) as specific markers of this disease as first-line diagnostic tests.

Background: Due to the increasing incidence of primary hyperparathyroidism (PHPT) in combination with associated complications and the potential risk of their further progression, timely screening and diagnosis of this disease are becoming an increasingly important task in real clinical practice. Early therapy of identified PHPT will prevent the development and progression of its severe complications and increase the duration and quality of life of patients.

Description of the clinical case: Patient S., 55, was followed-up for several years due to recurrent urolithiasis. In 2022, transurethral endoscopic laser fibrocalicolithotripsy was performed on the right. During an examination by an endocrinologist in 2024 regarding multinodular goiter, primary hyperparathyroidism was suspected, and therefore an examination to clarify the state of phosphorus-calcium metabolism was prescribed. During the examination, primary hyperparathyroidism and hypercalcemia were detected. According to the ultrasound examination, no formations were detected in the projection area of the parathyroid glands. In November 2024, transurethral endoscopic laser ureterolithotripsy, installation of an internal ureteral stent on the right, and percutaneous nephrolithotripsy with lithoextraction were performed. For the purpose of topical diagnostics of parathyroid adenoma, scintigraphy with three-dimensional single-photon emission computed tomography (hybrid SPECT-CT technology) of the parathyroid glands was performed, an adenoma of the ectopic right lower parathyroid gland was detected in the superior mediastinum. In January 2025, parathyroidectomy was performed. In the postoperative period, normalization of phosphorus-calcium metabolism parameters was recorded.

Conclusion: Primary hyperparathyroidism is an interdisciplinary problem, since it has quite variable clinical manifestations. Physicians of all specialties should be involved in the timely detection of PHPT.