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The pancreas belongs to the glands of mixed secretion and simultaneously performs both endo- and exocrine functions. Exocrine pancreatic insufficiency (EPI) is the general name for the malabsorption process caused by inadequate production and decreased activation of the enzymes of the pancreas acinar cells, such as amylase, lipase and protease, which are necessary for digestion. The prevalence of EPI in patients with type 1 diabetes, according to many authors, varies from 25 to 59%, which is determine by the data of pancreatic elastase-1. In this work, we present a clinical case of confirmed exocrine pancreatic insufficiency in a patient with a 6-year history of type 1 diabetes, which became the main cause of the development of episodes of hypoglycemia after meals. In the course of further studies, antibodies to lactoferrin and a reduced prostate volume, determined by MRI data, high levels of antibodies to glutamate decarboxylase and zinc co-transporter 8, as well as residual insulin secretion based on the level of C-peptide on an empty stomach detected.

BACKGROUND: Diabetic neuroosteoarthropathy (DNOAP, Charcot foot) is a relatively rare complication of diabetes mellitus (DM), which can lead not only to impaired support function of the lower limb in such patients, but also to high amputation. DNOAP is characterized by persistent aseptic inflammation of the bone structures of the foot, which creates significant ­difficulties in planning therapeutic measures. In the medical literature, there are data demonstrating the role of individual ­cytokines and neurohumoral factors in the prolongation of the inflammatory process in diabetes, however, there are currently very few studies that determine reliable markers of aseptic inflammation in DNOAP.AIM: To study the effect of neurohumoral factors and advanced glycation end products on the activity of aseptic inflammation in the bone structures of the foot in patients with type 2 diabetes mellitus (DM2) and diabetic neuroosteoarthropathy.MATERIALS AND METHODS. The study included 88 patients with type 2 diabetes (45 men, 43 women). Group 1 consisted of patients with DM2 and inactive DNOAP (n= 43), group 2 (n= 45) consisted of patients with DM2 and distal diabetic neuropathy without osteoarticular pathology. The diagnosis of diabetic neuropathy was based on the analysis of the clinical picture and indicators of peripheral sensitivity. Diagnosis of DNOAP and determination of its stage was based on clinical data, the results of infrared thermometry and radiology tests of the foot bones. General clinical assessment was used, radiology tests (X-ray, MRI), evaluation of CRP, calprotectin, copeptin, glutathione peroxidase 1 (GP1).RESULTS. According to the results of examination and palpation of the feet, as well as the analysis of the temperature gradient of the skin of the affected and contralateral limb (infrared thermometry), DNOAP was detected and the stage of this complication was determined. The diagnosis of the chronic stage of DNOAP was confirmed by the results of MRI and the clinical picture (no difference in skin temperature on the symmetrical areas of the feet). According to the results of laboratory analysis, a statistically significant difference in copeptin values was revealed — in group 1 — 0.232 µg/ml [0.147; 0.342], in group 2 — 0.115 µg/ml [0.065; 0.203] (p>0.05) and CRP — in group 1 — 7.113 mg/l [2.453; 16.505], in group 2 — 2.187 mg/l [1.131; 5.567] (p>0.05), leukocyte levels in the groups did not differ significantly: group 1 — 7.86 [6.40; 9.00]*10^9, group 2 — 7.00 [6.00; 8.15] (p>0.05). There was a trend towards an increase in the level of calprotectin and glutathione peroxidase-1 in the DNOAP group, however, the differences were not significant. calprotectin — in group 1 — 1.948 [1.229; 2.969], in group 2 — 1.692 [1.16; 2.514] μg/ml and glutathione peroxidase-1 in group 1 — 24.72 [20.1; 31.82], in group 2 — 22.98 [18.94; 31.2] ng/ml.CONCLUSION. In the study, statistically significant differences were obtained in the levels of copeptin and C-reactive protein: in patients with DNOAP, their values were significantly higher, which indicates the persistence of the aseptic inflammatory process in the bone tissue of patients even in the chronic stage of DNOAP. These data may help in deciding whether to use one or another method of unloading the affected joints, which will affect the clinical prognosis. The study of neurohumoral markers of arthropathy in the blood serum of patients with DM2 is carried out for the first time, and therefore it is difficult to compare with the results of other authors. It can be assumed that copeptin and CRP are significant markers of persistent inflammation of the osteoarticular structures of the foot in DNOAP.

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.

Backgraund: It believed that autoimmune process maintained only during the first 5 years of diabetes mellitus type 1 (T1D). Recently scientists discovered the high levels of islet autoantibodies (Ab) in long-standing T1D and some of these patients had residual insulin secretion, determined by the level of C-peptide. According to various sources, the prevalence of such observations ranges from 12 to 48%.Aims: The aim of our study was to assess the duration of autoimmune β-cells destruction markers persistence and residual fasting C-peptide secretion in the long-standing T1D, as well as to determine the possible causes and patterns of these processes.Materials and methods: In the study included 237 patients (91 men, 146 women) with T1D. Patients divided in 4 groups, according to disease duration: а — up to 1 year, n=69 (29%); b — 1–5 years, 52 (22%); c — 5–10 years, 57 (24%); d — more than 10 years, 59 (25%). Ab to glutamic acid decarboxylase (GADA), tyrosine phosphatase-like IA-2 (IA2) and zinc T8 (ZnT8A) were detected by Enzyme Immunoassay. Also detected C-peptide levels and retrospectively HbA1с.Results: Antibodies to antigens of β-cell components were detected in 26 (37%) patients in group A, in 17 patients (33%) in group B, in 15 (29%) in group C and in 14 (23%) — G.In the control group (n = 19), an increased level of antibodies was not revealed. Fasting C-peptide levels were as follows: in group «A» — 0.86 ng / ml [0.53; 1.4], «B» — 0.65 ng / ml [0.27; 0.98], « B «- 0.19 ng / ml [0.17; 0.33],» D «- 0.01 ng / ml [0.01; 0.01]. However, in 13 (22%) patients in group D, fasting C-peptide levels were more than 0.09 ng / ml.Conclusion: The data obtained indicate a long-term persistence of markers of the autoimmune process in patients with T1DM. In groups with a long (more than 5 years) course of T1DM, levels of fasting C-peptide more than 30 pmol/L (0.09 ng / ml or 0.03 nmol / L) were noted in 39 (33.6%) cases.

Rationale: In Russia, assessment of anti-P450c21 antibodies (AB) in the diagnosis of autoimmune adrenal insufficiency (AAI) has not been commonly used, and the disease screening has not been implemented.Aims: 1) To determine the sensitivity and specificity of anti-P450c21 AB determination in the AAI diagnosis; 2) To estimate the prevalence of anti-P450c21 AB carriage in patients without AAI.Materials and methods: Anti-P450c21 AB were assessed in 40 patients (group 1) with manifest AAI; 171 patients without established diagnosis of AAI, including 113 subjects with autoimmune thyroid disorders or type 1 diabetes mellitus (AID, group 2); 25 carriers of AB markers of thyroid AID and/or type 1 diabetes mellitus without any target organ dysfunctions (group 3); 33 patients with non-autoimmune endocrine disorders (group 4), and 25 healthy individuals (group 5).Results: Determination of anti-P450c21 AB for the diagnosis of AAI had 95% sensitivity, with specificity of 100%, predictive value of a positive result of 100%, and predictive value of a negative result 92.6%. Anti-P450c21 AB were inversely correlated with the duration of glucocorticoid replacement therapy (r=-0.222, p

Aim.To study an activity of the Renin-Angiotensin-Aldosterone System (RAAS) components in patients with primary hyperparathyroidism (PHPT) before and after parathyroidectomy (PTE). Materials and methods.A comparative study of patients with PHPT and control group. The first stage of the study included 56 patients with PHPT (group 1) before and on the third day after PTE. The second stage was carried out in 27 patients with remission of PHPT (group 2). All patients and healthy volunteers were tested for the main parameters of phosphorus-calcium metabolism and the RAAS parameters (plasma renin activity PRA, serum aldosterone, angiotensin II AT II). Results.Patients with active PHPT demonstrated changes in RAAS activity (lower PRA, higher AT II level) comparing to control group, that have statistical significance in group 1 (p0.001 for both parameters). There were no significant differences in aldosterone levels (p1=0.090;p2=0.140). On the third day after PTE (group 1), a decrease in aldosterone level (p=0.009) and a tendency to decrease in PRA (p=0.030) were detected. However, an increase in PRA (p=0.018), a decrease in AT II concentration (p=0.032) comparing to the initial values and their normalization were observed 12 months after surgery when permanent normal serum calcium and PTH levels had been achieved. There were controversial correlations between the parameters of phosphorus-calcium metabolism and RAAS. The influence of angiotensin-converting-enzyme inhibitors and AT II receptor blockers on phosphorus-calcium metabolism in patients with PHPT was not observed. Conclusion.In patients with PHPT, there were no сlear correlations of phosphorus-calcium metabolism parameters with RAAS, however an increase of AT II concentration was noted, that can take part in a development of hypertension for this endocrinopathy. PTE can have a positive effect on AT II level.

The steadily growing interest in studying of endocrine genetics is driven not only by the search for new pathologies but also by the most pressing need to develop methods for early diagnosis, treatment and management of patients. Though 20% of all the patients with von Hippel-Lindau syndrome do not have a family history of the disease; a genetic basis is a natural characteristic of the disease and determinates a phenotype. Despite the nonaggressive course, in general, a relative unpredictability of the syndrome signs onset and the lack of regular monitoring can increase the risk of surgery complications and cause a disability at a young age. The presented clinical case shows the need for a multidisciplinary approach to management of the patients with von Hippel-Lindau syndrome.