The first experience of using beta-hydroxybutyrate analysis of capillary blood in the diagnosis of non-diabetic hypoglycemia in adults

Background: The diagnostic threshold of β-hydroxybutyrate (BHB) at the moment of hypoglycemia in insulinoma was developed for venous blood many years ago, when there were no alternative ways to measure ketones. Number of works, mainly on patients with diabetes mellitus, found differences in the measurement of this indicator in venous and capillary blood, but the results were contradictory. Moreover, this study was not previously used in the diagnosis of non-diabetic hypoglycemia (NDH) in adults on the territory of the Russian Federation.Aim: To estimate the effectiveness of the method for determining BHB in capillary blood and its place in the diagnosis of NDH.Materials and methods: We conducted an experimental, cross-sectional, comparative study and included patients with suspected NDH who underwent a standard fast test. The BHB level in capillary blood was determined every 6 hours during the fast test and at its completion.Results: Based on the results of the fast test, the participants (n=154) were divided into groups: with hyperinsulinemic variant of NDH and IFRoma (n=98; group 1), with hypoinsulinemic variant of NDH /absence of NDH (n=56; group 2). When comparing the level of BHB at the moment of fasting completion, significant differences were obtained between groups 1 and 2 (p<0.001). According to the ROC analysis, the determination of BHB for differentiation the hyper- and hypoinsulinemic variants of hypoglycemia is characterized by excellent quality of model (AUC=99,1% [98,0%; 100,0%]). The BHB determination in capillary blood has the maximum diagnostic accuracy at a cut-off point of ≤ 1.4 mmol/L (Se 98.0%, Sp 96.4%, PPV 98.0%, NPV 96.4%, Ac 97.4%). Exceeding the diagnostic threshold of BHB was first recorded after 24h of fasting; at the same point, a significant difference was determined when comparing BHB indicators between two consecutive measurements (between 18h and 24h).Conclusion: The BHB determination in capillary blood is a highly sensitive and highly specific additional method for the differential diagnosis of NDH variants. The diagnostic threshold for BHB of capillary blood, which allows differentiating hyper- and hypoketonemic variants of NDH, is ≤1.4 mmol / L. It is advisable to initiate control of BHB in the blood no earlier than 18 hours after the start of the fast test

Transforming growth factor β1 (TGF-β1) in patients with endocrine ophthalmopathy and Graves’ disease: A predictor of treatment efficiency

Current therapeutic approaches to the treatment of endocrine ophthalmopathy (EOP) are based on nonspecific immunosuppression with glucocorticosteroids (GCs) and radiation therapy of the eye orbits. However, some patients exhibit resistance to the treatment. In a previous study, we have detected high levels of soluble cytokine receptors: sTNFα-R1, sTNFα-R2, sIL-2R, and the TGF-β1 cytokine in euthyroid patients with long-lasting non-treated EOP and Graves’ disease (GD). TGF-β1 level was significantly higher in the patients with EOP compared to healthy individuals, and increased with prolonged EOP duration, thus suggesting activation of the factors regulating immune system which promote suppression of the autoimmune process. The aim of this work was to study the dynamics of TGF-β1 and cytokine receptors: sTNFα-R1, sTNFα-R2, sIL-2R in the course of immunosuppressive therapy with high doses of GCs, as possible predictors of treatment efficacy. The study included 49 patients (98 eye orbits) with GD of euthyroid state and subclinical thyrotoxicosis, and the persons with EOP in active phase, who had not previously treatment for EOP. Concentrations of TGF-β1 cytokine, sTNFα-RI and sTNFα-R2, sIL-2R, antibodies to the thyroid-stimulating hormone receptor (rTSH), free fractions of thyroxine (fT4) and triiodothyronine (fT3), TSH in blood serum were determined in blood serum. Ultrasound examination of the thyroid gland (ultrasound of the thyroid gland), multi-layer computed tomography (MSCT)/magnetic resonance imaging (MRI) of the orbits were also performed. The patients were administered immunosuppressive therapy with high doses of HCs (methylprednisolone) in the course of pulse therapy, at a standard dosage of 4500-8000 mg, taking into account the severity and activity of the EOP clinical manifestations. The examination was carried out 3, 6, 12 months after starting the treatment. 3 and 6 months after the GC administration, more than 30% of patients remained resistant to treatment. The levels of TGF-β1 did not change significantly in the patients with positive EOP dynamics. In the patients resistant to GC treatment, the level of TGF-β1 was significantly decreased compared with patients who showed positive clinical dynamics. The level of sNFR1 and sNFaR2 did not change significantly. There were no significant differences in the levels of antibodies to rTSH, thyroid hormones in the patients resistant to GC treatment and with positive dynamics.Immunosuppressive therapy with high-dose of methylprednisolone in pulse therapy regimen showed high efficacy and good tolerability, while some patients remain resistant to treatment. Lower levels of TGF-β1 cytokine at initial time and during the treatment allow usage of TGF-β1 levels as a biomarker of the activity of the process, treatment efficiency, and prognosis of the disease. Activation of TGF-β1, a fibroblast growth factor, may contribute to the development of fibrosis, strabismus, and diplopia

Effect of glucocorticoids on bone metabolism in replacement therapy of adrenal insufficiency. Literature review

Adrenal insufficiency (AI) is a syndrome caused by disturbance in the synthesis and secretion of hormones of the adrenal cortex, which ensure the vital activity, energy and water-salt homeostasis. The widest hormonal deficiency is observed in primary hypocorticism, when the synthesis of not only glucocorticoids (GC) and adrenal androgens, but also mineralocorticoids is disrupted. Lifelong replacement therapy with GCs for this pathology may be associated with a risk of bone loss and osteoporosis. However, at present, there are no clear guidelines for diagnosis of bone condition, including and bone mineral density (BMD) monitoring during treatment with GCs in patients with AI. This review summarizes collected data on the key pathogenetic links of glucocorticoid-induced osteoporosis, incidence of decreased BMD and fractures in patients with AI. In this review factors that influence bone metabolism in this cohort of patients are considered: the type and the dose of prescribed GCs, the type (primary, secondary, HH in congenital adrenal cortex dysfunction) and the duration of AI, age, gender, and the presence of concomitant endocrine disorders (hypogonadism, growth hormone (GH) deficiency). In addition, the review presents data on the effect of adrenal androgen replacement therapy and recombinant GH therapy on bone metabolism in secondary AI

Опыт применения ритмической периферической магнитной стимуляции при пояснично-крестцовой радикулопатии

Introduction. Lumbosacral radiculopathy is а leading cause of long-term disability. Taking into a consideration the duration of treatment radiculopathy, the risk of developing adverse reactions when taking analgesics, non-steroidal anti-inflammatory drugs, the physiotherapeutic method — repetitive peripheral magnetic stimulation may become a promising method of therapy.Aim of the study. Assessment of the effectiveness of the complex treatment for patients with lumbosacral radiculopathy using the course of the repetitive peripheral magnetic stimulation.Materials and methods. Forty patients with lumbosacral radiculopathy were enrolled in the open non-randomized study, were divided into 2 parallel groups. The patients of the 1st group received a course of traditional treatment and a course of the repetitive peripheral magnetic stimulation. The patients of the 2nd group were treated with the traditional treatment without the course of the stimulation. A magnetic stimulator MagPro (Magventure, Denmark) was used for repetitive peripheral magnetic stimulation.Results. A significant difference (p <0.001) was registered regarding the reduction of pain syndrome and the improvement of the functional status after treatment in both groups. 14 (70 %) patients of the first group achieved a pain visual analogue scale relief by 50 % after 10 repetitive peripheral magnetic stimulation sessions, while 6 (30 %) patients did this after 15 repetitive peripheral magnetic stimulation sessions. We did not observed a statistically significant differences (p >0.05) in pain syndrome, functional status, anxiety level at the end of follow-up between the groups.Conclusion. We did not receive the benefits of the repetitive peripheral magnetic stimulation course in comparison with a traditional treatment of a lumbosacral radiculopathy. Further placebo-controlled studies to study the effect of repetitive peripheral magnetic stimulation on pain and anxiety in patients with back pain and radiculopathy are required.Введение. Пояснично-крестцовая радикулопатия является частой причиной стойкой и длительной утраты трудоспособности. Если принимать во внимание длительность лечения радикулопатии, риск развития нежелательных реакций при приеме анальгетиков и нестероидных противовоспалительных препаратов, перспективным направлением терапии становится применение физиотерапевтического метода — ритмической периферической магнитной стимуляции.Цель исследования – оценить эффективность комплексного лечения с применением курса ритмической периферической магнитной стимуляции у пациентов с пояснично-крестцовой радикулопатией.Материалы и методы. В открытом нерандомизированном исследовании приняли участие 40 пациентов с пояснично-крестцовой радикулопатией, которые были разделены на 2 группы. Пациенты 1-й группы получали курс традиционного лечения и курс ритмической периферической магнитной стимуляции. Больные 2-й группы — курс традиционного лечения без применения курса магнитной стимуляции. Для проведения стимуляции был использован магнитный стимулятор MagPro (Magventure, Дания).Результаты. Было показано достоверное различие (р <0,001) в отношении уменьшения интенсивности болевого синдрома, улучшения функционального статуса по окончании курса терапии в обеих группах. У 14 (70 %) пациентов 1-й группы уровень болевого синдрома уменьшился по визуально-аналоговой шкале на 50 % после 10 сессий ритмической периферической магнитной стимуляции, у 6 (30 %) больных — после 15 сессий. При оценке болевого синдрома, функционального статуса, уровня тревожности не было зарегистрировано статистически значимого различия (р >0,05) параметров между группами на момент завершения лечения.Заключение. Полученные результаты не показали преимущества курса ритмической периферической магнитной стимуляции у пациентов с пояснично-крестцовой радикулопатией в сравнении с курсом традиционной терапии. Требуются дальнейшие плацебо-контролируемые исследования для изучения влияния магнитной стимуляции на болевой синдром и уровень тревожности у пациентов с болью в спине и радикулопатией

Autoantibody levels in blood of <i>H. pylori</i>-infected patients with chronic gastritis

Helicobacter pylori (H. pylori) increases the risk of diseases associated with mucous membrane inflammation of gastrointestinal tract, in particular, gastritis, stomach ulcers, and duodenal ulcers. It may also induce a chronic immune response, causing damage to the mucous membrane and development of these diseases. In addition, the role of H. pylori in the initiation of a wide range of autoimmune diseases is discussed. The aim of this study was to assess the level of autoantibodies – markers of various autoimmune diseases in the blood of H. pylori-infected patients with chronic gastritis. We used samples of whole peripheral blood from 267 primary patients with chronic gastritis in the acute stage. The presence of H. pylori in gastric juice from patients was determined using real-time PCR. The level of autoantibodies to double-stranded and single-stranded DNA, autoantibodies to thyroglobulin, thyroid peroxidase, concentration of rheumatoid factor, IgG autoantibodies to the cyclic citrullinated peptide, IgM and IgG autoantibodies to beta(2)-glycoprotein were determined by the enzyme immunoassay. The average level of rheumatoid factor in blood serum was similar for H. pylori-infected and non-infected patients, and did not exceed the normal values. The level of antibodies to cyclic citrullinated peptide, one of the sensitive markers of rheumatoid arthritis, was increased in all patients, being, however, significantly lower in H. pylori-infected patients compared with non-infected persons. Autoantibodies to thyroglobulin, thyroid peroxidase are considered classic markers of autoimmune diseases of the thyroid gland. In blood of H. pylori-infected patients we have found an increased concentration of autoantibodies to thyroglobulin and thyroid peroxidase in comparison with non-infected ones, but the average level of these antibodies did not exceed the normal range. Any differences in the levels of systemic lupus erythematosus serological markers, i.e., autoantibodies to double-stranded and single-stranded DNA, were found between H. pylori-infected and non-infected patients. The levels of thrombosis risk marker in patients with systemic lupus erythematosus (IgG and IgM autoantibodies to beta(2)-glycoprotein) were also within the normal ranges. However, in H. pylori-infected patients, it even turned out to be statistically significantly lower than in non-infected ones. Thus, no data have been obtained on increased levels of the tested markers of autoimmune pathology in blood of H. pylori-infected patients with chronic gastritis at the acute stage. However, this does not allow us to make an unambiguous conclusion that the influence of H. pylori does not affect the development of immunological changes associated with autoimmune diseases

Russian clinical practice guidelines «congenital adrenal hyperplasia»

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases characterized by a defect in one of the enzymes or transport proteins involved in the cortisol synthesis in the adrenal cortex. The most common form of CAH, which occurs in more than 90% of cases, is a 21-hydroxylase enzyme deficiency. The latter is subdivided into nonclassical and classic (salt-losing and virilizing) forms. The prevalence of classic forms of 21-hydroxylase deficiency ranges from 1: 14,000 to 1:18,000 live births worldwide. According to the data of neonatal screening in the Russian Federation, the prevalence of the disease in some regions ranges from 1: 5000 to 1: 12000, in the country as a whole - 1: 9638 live newborns. The non-classical form of CAH occurs more often - from 1: 500 to 1: 1000 among the general population. In second place is the hypertensive form of CAH - a deficiency of 11β-hydroxylase, which, according to the literature, occurs in about 1 per 100,000 newborns. These clinical guidelines were compiled by a professional community of narrow specialists, approved by the expert council of the Ministry of Health of the Russian Federation, and updated the previous version published in 2016. The clinical guidelines are based on systematic reviews, meta-analyses and original articles, and scientific work on this issue in the Russian Federation and other countries. The purpose of this document is to provide clinicians with the most up-to-date, evidence-based guidelines for the CAH diagnosis and treatmen