Vol 21, No 4 (2019)


Updated clinical guidelines “Standards of specialized diabetes care”, 9th Edition. What is important

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Interview with Marina V. Shestakova.
Consilium Medicum. 2019;21(4):9-13
pages 9-13 views

Iodine deficiency thyroid disease in the Russian Federation: the current state of the problem. Аnalytical review of publications and data of official state statistics (Rosstat)

Melnichenko G.A., Troshina E.A., Platonova N.M., Panfilova E.A., Rybakova A.A., Abdulkhabirova F.M., Bostanova F.A.


Russian Federation refers to countries with proven natural iodine deficiency. Iodine deficiency disorders are pathological conditions that develop because of iodine deficiency in the diet, which can be prevented by normalization of its intake. Many counties of the world achieved significant decline in the incidence of thyropathies, associated with iodine deficiency, through the legislative of universal salt iodization, but in Russian Federation, this problem remains relevant. The aim of this review was to complain epidemiological characteristics of iodine deficiency-associated thyropathies in various regions of Russia, based on the analysis of the latest publications on this topic and the data provided by official statistics (Rosstat); we formulated conclusions. In Russia again registered an increase in the frequency of cretinism (severe mental retardation), associated with severe intrauterine iodine deficiency. Calculations show that about 1.5 million people in Russia may have mental retardation and related disability due to iodine deficiency in diet. Thus, the relevance and consequences of the iodine deficiency problem are obvious.
Consilium Medicum. 2019;21(4):14-20
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Subclinical hypothyroidizm and essential arterial hypertension: features of daily profiles of arterial stiffness in comorbid patients

Andreeva L.A., Panchenkova L.A., Troshina E.A., Khamidova K.A., Gagieva A.M.


Aim. To identify the features of the daily dynamics of arterial stiffness in patients with essential arterial hypertension (EАH) and subclinical hypothyroidism (SH). Material and methods. The study involved 78 patients with EAH aged 50 [42; 54] years, divided into 2 groups: AH - 48 (61.5%) and AH+SН - 30 (38.5%). The control group (CG) consisted of 30 healthy individuals, comparable in age and sex. All subjects underwent 24-hour daily monitoring of blood pressure (BPLab Vasotens, Russia) with recording daily arterial stiffness indicators: pulse wave velocity, PWVao; reflected wave transit time, RWTT; arterial stiffness index, ASI. The time index of the normal PWV (Pulse Time Index of Norm - PTIN) was calculated as a percentage of the 24-hour period during which the PWV does not exceed 10 m/s. The calculation of vascular age was carried out according to the Framingham SCORE risk scale modified according to D’Agostino. The comorbidity index was determined on a Charlson scale. Results. Analysis of the daily dynamics of arterial stiffness in patients with EAH and the presence of endocrine pathology showed that SН have a negative effect on elastic properties of the arteries, which is confirmed by significantly higher values of PWVao and arterial stiffness index, ASI, including at night, as well as lower PTIN indices compared with patients with isolated EAH. It can also be assumed that the worsening of arterial stiffness in the group of patients with AG+SН is more pronounced, given the significantly higher vascular age in this group of patients, associated with an increase in the number of comorbid pathology, compared with the AН group. Conclusion. The most pronounced deterioration of diurnal arterial stiffness indicators in the group of comorbid patients with EAH and SН, as well as the excess of vascular age over chronological and reliable correlation with the comorbidity index, revealed during the study, suggests an assessment of these indicators in patients with cardioendocrine pathology to assess the true risk cardiovascular complications and the selection of adequate therapy.
Consilium Medicum. 2019;21(4):21-25
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Results of the first Russian multicenter non-interventional study of Contour® TS glucometer

Shestakova M.V., Bolotskaya L.L., Verbovaia M.V., Lukina M.R., Rykova E.G., Ten E.O., Kupriianova-Ashina N.V., Tiunova E.S., Zhdanova E.A., Shabanova L.I., Taradaiko N.I., Malishevskaia A.S., Vachugova A.A., Sogomonian K.V.


Aim. To evaluate fitness of Contour® TS glucometer (Contour® TS, Bayer/Ascensia*) - a system for blood glycemia level control, and its characteristics in everyday use for Russian patients with insulin dependent diabetes mellitus (DM) types 1 and 2 and endocrinologists. Study design. According to the inclusion criteria, 3759 patients were registered in the program, of which 3599 patients have completed the study as per 3 visits. The non-interventional study was conducted in 84 medical centers in RF during the period from October 2013 to June 2015. Age of insulin-dependent patients and patients on hypoglycaemic therapy was 18 years and older. Results. Observational program included - 1126 (31.29%) patients with type 1 diabetes mellitus and 2473 (68.71%) patients with type 2 diabetes mellitus. Following switch to Contour® TS, while insulin therapy regimens were maintained, it was noted that the rate of blood glucose measurement increased compared with Visit 1 (p<0.0001). Upon assessment of satisfaction with the device, virtually all questions were answered as “good” and “perfect” by more than 90% patients and 95% study doctors. Upon assessment of the quality of life by EQ-5D, increase of this parameter was noted in 6 months, at Visit 3 (p<0.0001). No glucometer-associated malfunction were registered during the study. Additional data from general clinical experience of each patient that allowed to establish significant reduction of the levels of glycosilated haemoglobin and pre-prandial blood glucose just in 3 months at Visit 2, significant reduction of reported hypoglycaemia episodes as calculated per one patient have been obtained during the study. Additional data on the prevalence of macro- and microvascular complications were obtained during the study, and the highest per cent was for non-proliferative retinopathy and nephropathy at the stage of albuminuria. The most common among concomitant diseases were arterial hypertension, dyslipidemia and coronary artery disease. Conclusion. Use of Contour® TS glucometer by the patients, while insulin therapy regimens were maintained, led to increase in the rate of blood glucose measurements by up to 4-6 times during the day and statistically significant improvement in blood glucose control.
Consilium Medicum. 2019;21(4):26-34
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Nephroprotective properties of glucose-lowering drugs

Pokrovskaya E.V., Trubitsyna N.P., Zaytseva N.V.


Diabetic nephropathy is one of microvascular complications of diabetes mellitus, which is the leading cause of end-stage renal disease, requiring renal replacement therapy (dialysis, kidney transplantation). The quality and life expectancy of patients on dialysis is very low, and treatment requires significant material costs, therefore, a high priority is accorded to the prevention of the development and the progression of diabetic nephropathy. Primary prophylaxis is aimed at maintaining the target level of glycemia and glycated hemoglobin, blood pressure, lipid spectrum, for the secondary prevention, in addition to the above-mentioned indicators, drugs from RAAS blockers group are used. Also, in recent years, several classes of new glucose-lowering drugs (iSGLT-2, aGLP-1, iDPP-4) have appeared, affecting not only glycemia and metabolic parameters, but also renal function. In this review, we analyzed the results of large-scale international randomized trials designed to assess the nephroprotective properties of glucose-lowering drugs from the iSGLT-2, aGLP-1 and iDPP-4 groups. In studies with iSGLT-2 group, it is possible to speak of a class effect on the reduction of cardiovascular and renal risks and recommend their use for proven CVD and CKD. In the group of incretin drugs, one may infer, that they are cardiovascular safe, and in some studies, a positive effect on renal function in the form of reduced AU has been shown. Based on the data obtained, there is great interest in the study of the direct nephroprotective effect of these drugs, which may have a fundamental role in preventing the development and the progression of diabetic nephropathy.
Consilium Medicum. 2019;21(4):35-39
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Dipeptidyl peptidase-4 inhibitors use in clinical practice

Morgunova T.B., Fadeyev V.V.


According to modern view treatment of patients with diabetes mellitus is aimed not only at reaching target glycemic control levels but also at preventing development and progressing of late diabetes mellitus complications, improvement of quality of life and increase of life expectancy of patients. The relevance of the diabetes treatment research is explained with growing disorder prevalence including its prevalence in older population. Over the last years new classes of antihyperglycemic medications came into use: dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 agonists, and sodium-glucose linked transporter-2 inhibitors. Long-term experience of DPP-4 inhibitors use allows to conclude not only of effectiveness of medications of this class but also of their safety. Several studies of DPP-4 inhibitors use in older patients with comorbid disorders and renal impairment have been conducted including studies in real clinical practice. Results of studies of cardiovascular safety of medications from DPP-4 inhibitors class in patients with diabetes mellitus type 2 have been published. The article discusses the issues of antihyperglycemic therapy choice and the place of DPP-4 inhibitors in clinical practice.
Consilium Medicum. 2019;21(4):40-44
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Patient management with diabetes mellitus in outpatient practice: prevention and treatment of vascular and neurological complications

Morozova T.E., Konyshko N.A.


Diabetes mellitus (DM) is an actual problem of modern medicine, which is determined, on the one hand, by its high prevalence, on the other, by a high risk of developing microvascular and macrovascular complications. Treatment of patients with DM should be comprehensive and include, along with individually selected glucose-lowering drugs, drugs that can influence the pathogenetic mechanisms of the development of microvascular complications. Microvascular dysfunction and neuropathy are key links in the pathogenesis of insulin resistance, b-cell dysfunction, hyperglycemia, clinical and laboratory manifestations, complications, and comorbid diabetes relationships. The use of drugs with antioxidant properties (dipyridamole, thioctic acid), having a pathogenetic effect and preventing the development of microvascular dysfunction in standard therapeutic doses is pathogenetically justified in patients with DM complicated by diabetic angiopathy and neuropathy.
Consilium Medicum. 2019;21(4):45-49
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Endocrinological aspects of bariatric surgery

Troshina E.A., Ershova E.V., Mazurina N.V.


In the last decades all over the world surgical methods are used more widely for severe obesity treatment. A tendency is evident both in increase of the amount of operations and in increase of the number of countries where bariatric surgery becomes more widely spread. Indications and contraindications for bariatric surgery are presented in the guidelines including specific ones - in patients with type 2 diabetes mellitus (DM2). Different types of bariatric surgical interventions and mechanisms of influence on body mass, carbohydrate and lipid metabolism as well as main results in obese patients including ones with DM2 are described. The requirements for bariatric surgical interventions and parameters of their effectiveness estimation including DM2 remission are presented. The causes of postbariatric hypoglycemia and predictors of post-operation prognosis in relation to metabolic control in obese patients with DM2 are analyzed.
Consilium Medicum. 2019;21(4):50-55
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Mini-gastric bypass: is it a new operation of choice in metabolic surgery in diabetes mellitus type 2?

Sklyanik I.A., Karmadonov A.V., Shestakova M.V.


Relevance. The prevalence of diabetes mellitus type 2 (DM2) and obesity takes a pandemic form. Substantial progress had been made in pharmacotherapy for these disorders but there still are patients who develop complications caused by these disorders. A positive effect of metabolic surgery in patients with DM2 and obesity is well known. The review discusses the influence of mini-gastric bypass (MGP) on DM2 course and the possibility of DM2 remission. Materials and methods. A literature search was performed in Medline, Scopus, Web of Sciences, and RSCI databases with the use of key words: mini gastric bypass, single anastomosis gastric bypass, omega loop gastric bypass, loop gastric bypass, MGB, LMGB, мини-гастрошунтирование, гастрошунтирование с одним анастомозом. The search was performed in English and Russian. The search was performed for publications over the years 2001-2019. Results. A considerable improvement in DM2 course after MGP was shown. In 75-90% of cases DM2 remission could be achieved. The acquired results were not different and in some cases were better than those of traditional gastric bypass and were much better than results of sleeve gastrectomy. An increased risk of complications development was found neither in early nor in late postoperative period. Conclusion. MGB appears an effective bariatric operation and can be an operation of choice in patients with DM2 and obesity. Nevertheless it is reasonable to perform more prospective randomized controlled trials to determine additional metabolic advantages of MGB.
Consilium Medicum. 2019;21(4):56-58
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Medically induced hypoglycemia: focus on medications not included in the group of antihyperglycemic medications

Ostroumova O.D., Akimova E.S., Kochetkov A.I., Pereverzev A.P.


Recently, doctors face the problem of patients with hypoglycemia conditions caused by the use of drugs that are not drugs for the treatment of diabetes. This is due to the increase in the number of multimorbid diseases in people of older age groups and, consequently, an increase in the number of drugs used simultaneously (polypharmacy). Hypoglycemia can complicate the course of concomitant diseases, contributes to the occurrence of arrhythmias, increases the risk of cardiovascular events, cognitive impairment, including dementia, increases the frequency and duration of episodes of myocardial ischemia. Risk factors for the development of drug-induced hypoglycemia include: elderly and senile age; reduced glomerular filtration rate, liver failure (reduced gluconeogenesis), reduced food consumption (insufficient glucose consumption); excessive alcohol consumption (reduced gluconeogenesis, insufficient food intake); simultaneous intake of several drugs that can lead to hypoglycemia. The most frequently drug-induced hypoglycemia develops against the background of the use of quinolones, pentamidine, quinine, β-blockers, angiotensin-converting enzyme inhibitors and insulin-like growth factor. The main vehicle to prevent drug-induced hypoglycemia is to stop its use and/or replace it with another drug that does not have this side effect. If it is impossible to completely abandon the drug, it is necessary to minimize the risk of hypoglycemia in the following ways: use long-term administration of the same concentration of the drug (if possible, prolonged forms), reduce the dose of the drug (use the lowest possible effective doses), control the concentration of glucose in the blood.
Consilium Medicum. 2019;21(4):59-56
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Pharmacoeconomic aspects of the development of myocardial remodeling in patients with type 2 diabetes mellitus

Koroleva E.V., Khokhlov A.L., Sirotkina A.M.


Aim. Determine the relationship between the treatment and the development of left ventricular myocardial remodeling; conduct a pharmacoeconomic assessment of therapy in patients with type 2 diabetes. Materials and methods. The study included 208 patients with diabetes: group A (retrospective) - 105 patients, group B (prospective) - 103 patients. All patients received hypoglycemic and antihypertensive therapy. To determine the economic feasibility of using the drugs, the cost-effectiveness ratio (CER) was calculated. Results. The frequency of changes in the geometry of the heart increased in the absence of insulin therapy or on the background of PSGP monotherapy, as well as in the absence of ACE inhibitors, ARA II as antihypertensive therapy. NNT analysis showed greater efficacy and safety of alogliptin and empagliflozin. Our clinical and economic study also confirmed the greater efficacy of these drugs, but they turned out to be less economically acceptable compared to biguanides. Conclusion. The results of our study clearly demonstrate the dependence of the development of structural changes in the heart on the treatment of both primary and comorbid pathology in patients with type 2 diabetes, the most effective drugs from the IDPP-4 and AHHP-1 groups, as well as the ACE inhibitor and ARA II.
Consilium Medicum. 2019;21(4):66-69
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Insulin-producing tumor of pancreas in a young patient: the search for germline mutations. Clinical case

Yukina M.Y., Nuralieva N.F., Troshina E.A., Kaldarov A.R., Soldatova T.V., Vorontsov A.V., Vladimirova V.P., Tarbaeva N.V.


Insulinoma is the most common functioning tumor of the pancreas. Approximately 5% of cases of the disease is associated with the syndrome of multiple endocrine neoplasia type 1 (MEN-1), caused by mutation in the gene MEN1. The MEN-1 is manifested by pituitary adenomas and adenomas of parathyroid glands, pancreatic neuroendocrine tumors, tumors of thyroid gland, adrenal glands, intestine, carcinoids of lungs and other organs. Patients with MEN-1 often have angiofibromas, collagenomas and lipomas. However, in 5-10% of patients with clinical manifestations of this syndrome, mutations in MEN1 cannot be detected. In such cases, the disease can be caused by various disorders (mutations, polymorphisms, etc.) in other genes. More than 10 genes, associated with insulin-producing pancreatic tumor, are described in the literature. In the presented clinical case, an extended genetic study was performed in a young patient with insulinoma and a suspicious phenotype of MEN-1. The article emphasizes the need to search for new genetic markers that predispose to the development of insulinoma, and the subsequent introduction of panel of genes sequencing in such patients. Genetic testing is indicated primarily for young patients with multifocal lesions, family history and associated pathology.
Consilium Medicum. 2019;21(4):70-74
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On the safety of glucosamine sulfate in patients with insulin resistance

Gromova O.A., Torshin I.I., Lila A.M., Naumov A.V., Rudakov K.V.


Aim. Insulin resistance, metabolic syndrome and type 2 diabetes mellitus (T2DM) stimulate the development of chronic inflammation and make it difficult to rehabilitate patients with any comorbid pathology. In particular, T2DM impairs cartilage metabolism, leading to osteoarthritis (OA). For the treatment of arthropathogenic effects of diabetes mellitus, non-steroidal anti-inflammatory drugs (NSAIDs), drugs based on glucosamine sulfate (GS) and chondroitin sulfate (CS) are used. Materials and methods. Computer analysis of texts 21 777 publications. Results. GS is one of the safest OA therapies. Nexperimental and clinical studies have shown that HS can safely be used to treat OA in patients with type 2 diabetes. The anti-inflammatory effects of GS and the CS inhibition of O-acetylglucosamination processes by the molecules indicate the possibility of preventing the complications of type 2 diabetes. Conclusion. Despite the presence of the root "gluco" in the name of the GS, this substance does not stimulate the formation or progression of insulin resistance.
Consilium Medicum. 2019;21(4):75-83
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Vitamin D in the prevention of bone and metabolic disorders

Pigarova E.A., Mazurina N.V., Troshina E.A.


The lecture is addressed to doctors of various specialties and devoted to the role of vitamin D in the prevention of bone and metabolic disorders. Modern data on the physiological effects of vitamin D confirm its multifactorial effect on the skeletal and muscular systems, both direct and indirect. The mutual influence of obesity and vitamin D deficiency is determined by several mechanisms, while the decrease in the bioavailability of vitamin D in obesity causes the development of secondary hyperparathyroidism. The existing algorithms for prevention and treatment of vitamin D deficiency involve not only the initial level of 25(OH)D, but also the patient's age, body mass index, and the presence of concomitant diseases. Modern clinical guidelines of the Russian Association of Endocrinologists on prevention and treatment of vitamin D deficiency are an effective instrument in patients’ management. For prevention and treatment of vitamin D deficiency in obese patients higher doses of colecalciferol are required. In adult patients it is recommended to start correction of vitamin D deficiency (lower than 20 ng/ml) and insufficiency (20-29 ng/ml) with a saturating colecalciferol dose with further switch to the use of maintenance doses. Saturation can be conducted with the use of various therapy regimens.
Consilium Medicum. 2019;21(4):84-90
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Polyglandular autoimmune syndrome in adults: molecular genetic and clinical characteristics (lecture)

Troshina E.A., Larina A.A., Terekhova M.A.


Endocrine system disorders (diabetes mellitus, thyroid gland pathologies, polyglandular autoimmune syndromes, adrenal insufficiency, autoimmune ophthalmopathy and others) in development of which immune response disorders play an important role are among the most severe chronic human diseases prevention and early diagnostics of which are often hampered by disease clinical course latent phases. Polyglandular autoimmune syndromes (PAS) comprise damage of two or more endocrine glands characterized with multiple organ failure. In Russian classification the syndrome is divided into 2 main subtypes: PAS type 1 (the prevalence varies from 1:9 thousands to 1 per 200 thousands population) and PAS type 2 (the prevalence is 1.4-4.5 cases per 100 thousands population). Other classifications comprise hidden (latent and potential) forms of the disorder. Patients with PAS are a special cohort that requires careful monitoring and regular screening for prognosis and detection of new components of PAS. High prevalence and incidence rates, disabling complications, and reproductive losses - all of these are common in autoimmune endocrinopathies and are an important challenge at present. The lecture summarizes key clinical and diagnostic characteristics of PAS, proposes practical approach to these syndromes treatment, and specifies key laboratory markers for the disorder dynamics monitoring.
Consilium Medicum. 2019;21(4):91-96
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Markers and genetic predictors of osteoporosis in routine clinical practice

Grebennikova T.A., Troshina V.V., Belaia Z.E.


The review aimed to provide information on main characteristics of calcium and phosphate metabolism, osteoporosis markers, genetic predictors of the disorder and their significance in clinical practice. Osteoporosis is a common problem of public healthcare that is often underestimated. The disorder is often diagnosed retrospectively after a fragility fracture. About 25% of fragility fractures are associated with secondary osteoporosis or with other causes of calcium and phosphorus metabolism disorders. Estimation of main indicators of calcium and phosphate metabolism: calcium and phosphorus is necessary for osteoporosis differential diagnosis. Markers of bone remodeling such as bone-specific alkaline phosphatase, osteocalcin, N-terminal propeptide of type 1 procollagen, and C-terminal telopeptide of type 1 collagen are important in dynamics assessment of osteoporosis treatment effectiveness and should be used more widely. The use of COL1A1, CALCR, VDR genes polymorphisms analysis for assessment of susceptibility to osteoporosis development is a question under consideration and requires further investigations. In order to write this review we analyzed Russian and foreign literature mostly published in the last 5 years and dedicated to the problem of osteoporosis. On the basis of literature study a deep understanding of specificities of the use of calcium and phosphate metabolism characteristics, osteoporosis markers and gene polymorphism in routine clinical practice was formed. Therefore, the presented material is quite practical for clinical physicians.
Consilium Medicum. 2019;21(4):97-102
pages 97-102 views

Chronic adrenal insufficiency in clinical practice

Biryukova E.V., Ganenkova E.S., Lovanova M.D.


Aim. To present causes, pathogenesis, clinical presentation, diagnostics and treatment of chronic adrenal insufficiency. Materials and methods. Data from 23 scientific sources published in Russia and abroad in years 1985-2017 are presented. Results. Although adrenal insufficiency is a rare endocrine system disorder, early diagnostics and treatment of adrenal insufficiency (AI) is of great importance in clinical practice because this is a life-threatening disorder when not treated. Depending on the level of hypothalamic-pituitary-adrenal system damage, primary (PAI), secondary (SAI) and tertiary adrenal insufficiency are distinguished. The main cause of PAI (80-90%) is an autoimmune destruction of adrenal cortex (autoimmune adrenalitis): isolated damage or a part of autoimmune polyglandular syndrome. Adrenal glands damage can also develop as a result of various factors: infections (tuberculosis, fungous and cytomegalovirus infections), tumors (malignant tumors or metastases), adrenalectomy, and adrenoleukodystrophy. The most frequent cause of SAI is glucocorticoids therapy in pharmacological doses, timorous and destructive processes in pituitary-hypothalamic area that result in ACTH production decrease and suppression. Clinical presentation is not a highly specific criterion of CAI diagnostics and requires confirmation with laboratory results. AI clinical manifestations aggravate in association with stressful situations, intercurrent diseases, high fever, and surgical interventions. A patient with chronic primary adrenal insufficiency needs constant replacement therapy with glucocorticoids and, in most cases with mineralocorticoids. Conclusion. Awareness of AI clinical presentation and modern diagnostic methods will allow diagnosing the disease on time and prescribing replacement therapy.
Consilium Medicum. 2019;21(4):103-108
pages 103-108 views

Adrenal vein sampling in differential diagnosis of primary aldosteronism on the example of a clinical case

Sitkin I.I., Romanova N.Y., Platonova N.M., Molashenko N.V., Troshina E.A.


Primary aldosteronism is the most common cause of endocrine hypertension, occurring in 5-10% of patients with hypertension. Convincing evidence has been obtained indicating that primary aldosteronism increases the risk of cardiovascular complications, respectively, early diagnosis and treatment of patients with the definition of further tactics is a key step to prevent the progression of cardiovascular complications. The choice of the most appropriate treatment method for patients with primary aldosteronism depends on the diagnosis of nosological subtypes - bilateral adrenal hyperplasia (also known as idiopathic aldosteronism), which recommends a conservative treatment or unilateral aldosteronism due to aldosterone-producing adenoma, in which surgical treatment (adrenalectomy) is the tactic of choice. In addition, the "obvious" adrenal adenomas may in fact turn out to be areas of focal hyperplasia - a diagnostic error in this case leads to the unreasonable implementation of adrenalectomy. In order to clarify the lateralization of aldosterone hyperproduction, adrenal venous sampling is used. However, this method requires constant radiography, qualified endovascular surgery and is carried out in centralized medical hospitals. In this clinical case, we want to demonstrate the importance of a diagnosis of primary aldosteronism step by step.
Consilium Medicum. 2019;21(4):109-113
pages 109-113 views

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