[Association between preoperative cholecalciferol therapy and hypocalcemia after parathyroidectomy in patients with primary hyperparathyroidism].

BACKGROUND: Primary hyperparathyroidism (PHPT) is a endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) from parathyroid gland tumors. Parathyroidectomy (PTE) is the main treatment for PHPT, but it can lead to hypocalcemia in up to 46% of cases. Hypocalcemia is associated with seizures and life-threatening cardiac arrhythmias, and vitamin D deficiency can exacerbate PHPT severity and contribute to «hungry bones syndrome,¼ resulting in severe and persistent postoperative hypocalcemia. AIM: To evaluate the association and determine the strength of the relationship between preoperative cholecalciferol therapy and the occurrence of hypocalcemia within 1-3 days after PTE in patients with PHPT. MATERIALS AND METHODS: The study was conducted at the Endocrinology Research Centre, during the periods of 1993-2010 and 2017-2020. The inclusion criteria consisted of patients diagnosed with PHPT who required PTE, had a serum 25-hydroxyvitamin D (25(OH)D) level below 20 ng/mL, and a serum total calcium level below 3 mmol/L. The exclusion criterion was the use of medications that affect calcium-phosphorus metabolism, including cinacalcet, denosumab, or bisphosphonates, either as monotherapy or as part of combination therapy. RESULTS: There were 117 patients, including 110 (94%) females and 7 (6%) males. The median age and interquartile range were 58 [49; 65] years. Among the participants, 21 (18%) received cholecalciferol supplementation for a duration of 2 weeks to 2 months prior to PTE, aiming to address vitamin D deficiency. The remaining 96 (82%) participants did not receive -cholecalciferol supplementation. Both groups, i.e., participants receiving cholecalciferol and those who did not, were similar in terms of anthropometric factors (sex and age at the time of surgery), preoperative clinical characteristics (BMD decrease), and laboratory parameters (PTH, total calcium, phosphorus, ALP, OC, CTX-1, and 25(OH)D levels). The occurrence of postoperative hypocalcemia was significantly lower in participants who received cholecalciferol supplementation (10% vs. 63%, p<0,001, FET2). Cholecalciferol intake showed a negative association with hypocalcemia development (RR=0,15, 95% CI (0,03; 0,51)). CONCLUSION: Preoperative cholecalciferol supplementation for 2 weeks to 2 months before PTE reduces the risk of postoperative hypocalcemia in patients with PHPT by 2-33 times.

[Comparative analysis of bone complications/manifestations in sporadic and MEN1-related primary hyperparathyroidism].

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) - is a rare syndrome with an autosomal dominant inheritance pattern caused by a mutation in the tumor suppressor gene (MEN1). Parathyroid involvement is the most common MEN1 manifestation resulting in primary hyperparathyroidism (mPHPT). Data on the prevalence and structure of bone disease in mPHPT compared to sporadic one (sPHPT) are often incomplete and contradictory. AIM: The purpose of this study was to compare the severity of bone involvement between mPHPT and sPHPT. MATERIALS AND METHODS: A single-center retrospective study was conducted among young patients in the active phase of PHPT and without prior parathyroidectomy in anamnesis. The analysis included the main parameters of calcium-phosphorus metabolism, bone remodeling markers, as well as an assessment of disease complications. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) at sites of lumbar spine, femur and radius. Trabecular bone score (TBS) was applied to estimate trabecular microarchitecture. All patients included in the study underwent genetic testing. RESULTS: Group 1 (mPHPT) included 26 patients, and group 2 (sSHPT) included 30 age-matched patients: the median age in group 1 was 34.5 years [25; 39], in group 2 - 30.5 years [28; 36], (p=0.439, U-test). Within group 1, the subgroup 1A (n=21) was formed with patients without other hormone-produced neuroendocrine neoplasms (NEN) in the gastrointestinal tract (GI) and the anterior pituitary gland. The duration of PHPT was comparable in both groups: mPHPT - 1 year [0; 3] versus sPHPT - 1 year [0; 1], (p=0.533, U-test). There were no differences in the main parameters of calcium-phosphorus metabolism, as well as in the prevalence of kidney complications. In the mPHPT group, bone abnormalities were observed significantly more often compared to sPHPT: 54 vs 10% (p=<0.001; F-test). Statistically significant differences were revealed both in BMD and in Z-score values of the femoral neck and total hip, which were lower in the mPHPT group. These differences remained significant when comparing subgroup 1A with sPHPT. CONCLUSION: MEN1-associated PHPT may be accompanied by a more severe decrease in BMD in the femoral neck and total hip compared to sPHPT regardless of the other hormone-producing NEN. Clarifying the role of mutation in the MEN1 gene in these processes requires further study.

[Predicting the presence of MEN1 gene mutation based on the clinical phenotype of patients with primary hyperparathyroidism].

BACKGROUND: Timely referral of patients for genetic testing to rule out MEN1-associated primary PHPT is important factor in determining treatment strategy and prognosis. In the context of the limited availability of genetic testing, the search for clinical markers indicative of MEN1 gene mutations remains an extremely relevant task. AIM: To determine the diagnostic value of clinical features of primary PHPT in young patients for predicting the presence of MEN1 gene mutations. MATERIALS AND METHODS: A single-center, prospective study was conducted at the Endocrinology Research Centre, involving 273 patients with PHPT in the period 2015-2022. Based on the results of genetic and laboratory tests, patients were divided into three groups: those with MEN1 gene mutations (MEN+ group, n=71), those without MEN1 gene mutations - isolated sporadic PHPT (MEN- group, n=158), and patients with PHPT and associated endocrine gland disorders - MEN-1 syndrome phenocopies (PHEN group, n=32). Subgroups of patients younger than 40 years of age were also identified. Comparative analysis was performed among the independent groups and subgroups, and logistic regression analysis was used to develop a mathematical model for predicting the probability of the presence of MEN1 gene mutation. RESULTS: Patients in the MEN+ and MEN- groups were comparable by gender and age at manifestation, as well as calcium-phosphorus metabolism parameters and PHPT complications. In the PHEN group, PHPT manifested at older age compared to the other groups (p<0.001 for all), with lower total calcium levels and a trend toward lower iPTH concentrations. The MEN+ group had a significantly higher frequency of multiglandular parathyroid (PG) involvement, PHPT recurrence, and positive family history compared to the MEN- and PHEN groups. Histologically, adenomas predominated in the PHEN and MEN- groups (92% and 94%, respectively), whereas hyperplasia of PGs were more common in the MEN+ group (49%). None of the PHEN patients had all three «classic¼ components of the MEN-1 syndrome, and the clinical course of PHPT was similar to that of the MEN- group. These differences were also observed in the subgroups of patients younger than 40 years, which formed the basis for the development of a mathematical model. The logistic regression equation for predicting the probability of the presence of the MEN1 gene mutation included eight predictors, with a diagnostic sensitivity of 96% and specificity of 98%. CONCLUSION: Based on the analysis performed, eight hereditary predictors of PHPT within the MEN-1 syndrome were identified. A mathematical model was developed to predict the presence of the MEN1 gene mutation in patients, which demonstrated high classification performance on the training dataset. Further refinement of the model will help improve the quality of medical care for patients with PHPT.

[Dynamics the parameters of mineral metabolism in hospitalized patients with COVID-19, the impact of etiotropic and pathogenetic therapy].

The high prevalence of COVID-19 requires the research progress on the disease pathogenesis. There is a lot of data confirming the association between mineral metabolism and the severity of COVID-19. AIM: To study the dynamics of mineral metabolism parameters in patients with a confirmed COVID-19 at the time of hospitalization and after discharge, including the impact of etiotropic and pathogenetic therapy on them. MATERIALS AND METHODS: A single-center study of 106 patients (aged ≥18 years) with clinically or laboratory confirmed diagnosis of COVID-19 was carried out at the Endocrinology Research Centre, Moscow. Baseline biochemical parameters, including serum calcium, phosphorus, albumin, 25(OH)D, parathyroid hormone (PTH), inflammatory markers, and instrumental assessment of COVID-19 severity were performed before specific immunotherapy, as well as on 3rd and 7th days of hospitalization and before discharge. Statistical analysis was performed with Statistica 13 software (StatSoft, USA). RESULTS: On the first day, hypocalcemia (low albumin-adjusted calcium level) was detected in 40.6% of cases, the prevalence of vitamin D deficiency/insufficiency amounted to 95.3% of cases. At the same time, secondary hyperparathyroidism was identified only in 14.2% of patients. A comparative analysis of mineral metabolism during hospitalization (between 1, 3, 7 days of hospitalization and before discharge) during baricitinib treatment revealed a statistically significant increase in albumin-adjusted calcium by the end of hospitalization (p<0.001, Friedman criterion, Bonferroni correction p0=0.01). A pairwise comparison of subgroups, depending on the therapy, revealed a statistically significantly lower level of albumin-adjusted calcium on 3rd day among patients on baricitinib monotherapy or combined with tocilizumab compared with a subgroup of patients undergoing etiotropic treatment (2.16 [2.13; 2.18] mmol/l vs 2.23 [2.19; 2.28] mmol/l, p=0.002, U-test, Bonferroni correction p0=0.012). CONCLUSION: Patients with severe coronavirus infection are characterized by a high prevalence of vitamin D deficiency and hypocalcemia. Associations between calcium and saturation as well as the severity of lung lesion characterizes hypocalcemia as an important predictor of severe course and poor outcome in COVID-19. Pathogenetic therapy with baricitinib, including in combination with tocilizumab, contributes to achieve normocalcemia, but further studies are required.

[Casuistic cases of parathyroid carcinoma with a verified mutation in the MEN1 gene].

Parathyroid cancer (PTC) is usually sporadic; however, it could be presented as a component of hereditary syndromes. The prevalence of PTC among patients with primary hyperparathyroidism (PHPT) is about 1% cases. The lack of reliable preoperative predictors significantly complicates the diagnosis of PTC. The clinical course is non-specific and in most cases is determined by severe hypercalcemia. The final diagnosis can only be made on the basis of invasive histopathologic features, while an analysis immunohistochemical (IHC) one can be used only as an additional method. Given the rarity the diagnosis of MEN1-related PTC a challenge. We present two clinical cases of patients with PTC and a verified heterozygous mutation in the MEN1 gene. The described cases demonstrate the complexity of morphological diagnosis for PTC, the heterogeneity of clinical manifestations in patients with the MEN1 mutation, as well as the need for timely screening to identify other components of MEN1 syndrome and mutations of the MEN1 gene among first-line relatives.

[Experience in using teriparatide for the treatment of postoperative hypoparathyroidism in hemodialysis patients].

The frequency of chronic postoperative hypoparathyroidism after total parathyroidectomy for secondary and tertiary hyperparathyroidism in patients with end-stage renal failure, according to various authors, can reach 20% or more. Prescribing active metabolites of vitamin D and calcium it is not always sufficient for achievement of target goals. This dictates the need for replacement therapy with recombinant parathyroid hormone. Teriparatide is the only drug of this series approved by the American Food and Drug Administration (FDA) and registered in the Russian Federation. However, it is registered as an anabolic anti-osteoporotic drug and is not indicated for the treatment of chronic hypoparathyroidism. The use of teriparatide in postoperative hypoparathyroidism in patients receiving renal replacement therapy with programmed hemodialysis in the Russian Federation has not been previously studied. Data on this issue is also limited in foreign literature. However, it is a potential treatment option for hemodialysis patients with chronic hypoparathyroidism and severe bone disorders. In this article, we present 2 clinical cases of substitution and anabolic therapy with teriparatide in this cohort of patients.

[The short test with hydrochlorothiazide in differential diagnosis between primary normocalcemic and secondary hyperparathyroidism for inpatient treatment].

BACKGROUND: Differential diagnosis between the normocalcemic primary hyperparathyroidism (nPHPT) and secondary hyperparathyroidism (SHPT) due to hypercalciuria remains a challenge. AIM: The aim of this study was to investigate the capability of short test with hydrochlorothiazide for the differential diagnosis of nPHPT and SHPT. MATERIALS AND METHODS: A retrospective study was conducted with the participation of 28 patients who underwent a functional test with thiazide diuretics during hospitalization in the Department of parathyroid glands pathology and mineral disorders of the Endocrinology Research Centre, Russia. Parameters of mineral metabolism were evaluated before and 3-5 days after taking hydrochlorothiazide 50 mg/day. RESULTS: According to baseline and dynamic biochemical evaluation patients were divided into 3 groups. Group 1 (n=21) included patients with confirmed PHPT, who reached hypercalcemia accompanying with an elevated level of iPTH (n=19) or an increased level of iPTH accompanying with normocalcemia (n=2). In group 1, baseline Caadj. was 2.48 mmol/l [2.47; 2.52], iPTH 107.5 pg/ml [86.8; 133.0], after short test - 2.63 mmol/l [2.59; 2.66] and 102.1 pg/ml [95,7; 124,1]. Group 2 included only one who was diagnosed with SHPT, a normal value of iPTH with concomitant normocalcemia was achieved after 4 days of hydrochlorothiazide therapy (baseline Caadj. 2.35 mmol/l, iPTH 74.5 pg/ml vs at 2.27 mmol/l and 50.7 pg/ml respectively). Patients with doubtful results of the test entered in group 3 (n=6), they did not achieve significant changes in the calcium and iPTH levels, so it was recommended to continue the test on an outpatient basis (baseline Caadj. 2.39 mmol/l [2.33;2.45], iPTH 97.0 pg/ml [83.1;117.0]); after short test - 2.47 mmol/l [2.42; 2.48] and 91.3 pg/ml [86.9; 124.0] respectively). Groups with PHPT and SHPT and doubtful results significantly differed from each other in Caadj (р=0.003, U-test, Bonferroni correction Р0=0.006), but not in iPTH, daily calciuria, eGFR, and phosphorus. There were no significant differences in the incidence of classical complications of PHPT. CONCLUSION: The diagnosis of PHPT was confirmed in 21/28 patients 3-5 days after taking hydrochlorothiazide 50 mg/day. The obtained results are significant for the differential diagnosis in hospitalized patients with an unspecified genesis of hyperparathyroidism.

[Severe bone complications of primary hyperparathyroidism in a young patient with the rare verified mutation of MEN1].

Multiple endocrine neoplasia type 1 syndrome (MEN1) is a rare inherited disorder that can include combinations of more than 20 endocrine and non-endocrine tumors. Unfortunately, none of the described MEN1 mutations has been associated with a peculiar clinical phenotype, even within members of the same family, thus a genotype-to-phenotype correlation does not exist. MEN1 syndrome is the most common cause of hereditary primary hyperparathyroidism (PHPT), the disease penetrance of which exceeds 50% by the age of 20 and reaches 95% by the age of 40. At the same time, PHPT with hyperplasia or adenomas of the parathyroid glands (PTG) is the most distinctive manifestation of the MEN1 syndrome. One of the main symptoms of PHPT, both in sporadic and hereditary forms of the disease, is bone damage. At the time of diagnosis in PHPT/MEN1, the bone mineral density is generally lower in comparison with the sporadic form of PHPT. This may be due to excessive secretion of parathyroid hormone during the period of peak bone mass, concomitant components of the syndrome, extended surgical treatment, and the direct effect of a mutation in the menin gene on bone remodeling. This clinical case describes a young patient with severe bone complications of PHPT and uncertain rare MEN1 mutation. PHPT was diagnosed five years later from the first onset of bone complications and repeated orthopedic operations. There was the «hungry bones¼ syndrome after successful surgery of PHPT, which was managed with vitamin D and calcium carbonate supplementation and there is a positive dynamic in increased bone mineral density in the main skeleton after 6 months.

[Case of clinically "aggressive" course of primary hyperparathyroidism, algorithm of differential diagnosis].

Primary hyperparathyroidism (PHPT) is a significant endocrine disease caused by increased production of parathyroid hormone (PTH) by altered parathyroid glands and violation of the mechanisms of regulation of serum calcium concentrations. These changes can lead to nephrolithiasis, osteoporosis, erosive and ulcerative lesions of the gastrointestinal tract, a number of less specific symptoms (nausea, vomiting, weakness, fatigue, etc.). Etiologically, in more than 85% of cases, PHPT is a consequence of sporadic solitary adenoma or hyperplasia parathyroid glands, however, in 1-3% of cases, the cause is carcinoma of parathyroid glands , including as part of various genetic syndromes. The importance of timely examination for PHPT of patients with characteristic clinical manifestations of this disease and - with an aggressive course - alertness towards carcinomas of parathyroid glands was noted. At the same time, the severity of the clinical picture and even the presence of suspicious signs characteristic of hereditary forms of carcinomas of parathyroid glands are not always a consequence of the malignant process. We present a description of a young patient with a severe course of PHPT, multiple fractures and a voluminous tumor of the upper jaw, developed as a result of a typical adenoma of parathyroid glands. Additionally, the algorithm of pre- and postoperative differential diagnosis for such patients is highlighted.

[Assessment of the prevalence of anemia in patients with primary hyperparathyroidism: a single-center observational study].

BACKGROUND: The combination of primary hyperparathyroidism (PHPT) with anemia was first described in 1931. It remains unclear whether PHPT is the direct cause of anemia, or it develops due to PHPT's complications. The frequency of PHPT--associated anemia in the Russian population is unknown. AIM: To assess the prevalence of anemia in patients with PHPT admitted to the Department of Parathyroid Glands Pathology in the Endocrinology Research Centre from January 2017 to August 2020. MATERIALS AND METHODS: The study included patients with PHPT over 18 years old. A single-center observational one-stage one-sample uncontrolled study was carried out. We analyzed laboratory and instrumental data obtained during inpatient examination in accordance with the standards of medical care. Statistical analysis was performed using Statistica 13 (StatSoft, USA) and SPSS (IBM, USA) software packages. RESULTS: The study included 327 patients with PHPT, 28 (9%) men and 299 (91%) women. The median age was 59 years [51; 66]. 26 patients (8%) with anemia were identified. Statistically significant differences between patients with and without anemia were found only in the GFR. Comparison of patients with and without anemia didn't reveal any significant differences in the incidence of PHPT's complications.Significant differences in serum hemoglobin concentration and average hemoglobin concentration in erythrocytes were revealed between patients with and without vertebrae fractures. In the group of patients without compression fractures these parameters were higher.In the subgroup of patients with total calcium concentration above 3 mmol/L and PTH above 3 normal values, the incidence of anemia reached 21% (95% CI: 10%; 35%). Within this group we revealed tendencies to higher levels of PTH, ionized calcium and osteocalcin in patients with anemia. CONCLUSION: In general, there was no correlation between hypercalcemia, the degree of PTH elevation and the presence of anemia in patients with PHPT. However, in the subgroup of patients with severe hypercalcemia, there was a relationship between the concentration of PTH, ionized calcium and the presence of anemia. In patients with PHPT and vertebral fractures, significantly lower concentrations of blood hemoglobin and hemoglobin in erythrocytes were observed.

[Registries of parathyroid glands diseases in the Russian Federation].

The most important and effective way to organize nationwide the healthcare, as well as monitoring and routing for patients with endocrine diseases, is the creation of an unified medical record (Endocard). The Endocard is also aimed at maximizing the opportunity for professionals and researchers on various scientific issues. Registries are the potential informational and analytical platform to achieve this goal. They include the basic information on the epidemiological and clinical features of the most severe diseases such as diabetes mellitus. Given the lack of large-scale epidemiological data on the parathyroid glands pathology - primary hyperparathyroidism and hypoparathyroidism - the registers of these diseases that collects a common dataset and clinician and patient reported outcomes are of particular interest.

[The Russian registry of chronic hypoparathyroidism and clinical decision support system integration].

According to available research, chronic hypoparathyroidism is a relatively rare disease characterized by low serum calcium levels and the absence or deficiency of parathyroid hormone. The chronic course of the disease is associated with the multicomponent medical therapy, careful dynamic monitoring to reduce the risks of various complications in different organs and systems as well as disability and mortality.The Russian registry of patients with chronic postsurgical and nonsurgical hypoparathyroidism has started its work in 2020, based on data of the Endocrinology Research Centre. The main goals of the Registry are the assessment of the actual prevalence, incidence of hypoparathyroidism, the key epidemiological characteristics, the analysis of the clinical features and medical therapy of chronic hypoparathyroidism in Russian Federation.This article covers all objectives of this project, the methodology for maintaining the registry of chronic postsurgical and nonsurgical hypoparathyroidism, the analytical possibilities of its use, including the integration of a decision support system designed to help specialists in real clinical practice follow the algorithms for diagnosis and treatment of the disease, approved by clinical guidelines.The registry of chronic postsurgical and nonsurgical hypoparathyroidism is located on a single platform for the registers of endocrinopathies, regulated by the Endocrinology Research Centre (http://gipopt.clin-reg.ru/).

[Review of clinical practice guidelines for hypoparathyroidism].

Hypoparathyroidism is a rare disorder characterized by the absent or inappropriately decreased serum parathyroid hormone in the parathyroid glands, which is accompanied by impaired calcium-phosphorus metabolism.The main etiology of hypoparathyroidism remains damage or removal of the parathyroid glands during neck surgery. In view of the incidence of thyroid cancer, primary hyperparathyroidism and other pathologies of the neck organs, which radical treatment can lead to the parathyroid gland impairment, an increased number of patients with hypoparathyroidism is expected. Autoimmune hypoparathyroidism is the second most common form of the disease, usually occurring as part of type 1 autoimmune polyglandular syndrome. Autoimmune hypoparathyroidism usually occurs in childhood and is characterized by a severe course of the disease, especially in the case of concomitant malabsorption syndrome.Chronic hypoparathyroidism of any etiology requires lifelong multicomponent therapy, as well as careful monitoring and an individual approach to choose the optimal treatment strategy. In the absence of adequate follow-up, the risks of long-term complications significantly increase, particularly in the renal, cardiovascular systems; in the soft tissues and in the brain, it could lead to visual disturbances; pathology of the musculoskeletal system with a decreased bone remodeling and a potential risk of fractures, as well as to the neurocognitive disorders and an impaired health-related quality of life.Timely diagnosis, rational medical therapy and management strategy may reduce the risks of short-term and long-term complications, frequency of hospitalizations and disability of patients, as well as improve the prognosis.This review covers the main issues of Russian guidelines for the management of chronic hypoparathyroidism, approved in 2021, including laboratory and instrumental evaluation, treatment approaches and follow-up. This guidelines also include the recommendations for special groups of patients: with acute hypocalcemia, hypoparathyroidism during pregnancy.

[The clinical practice guidelines for primary hyperparathyroidism, short version].

Primary hyperparathyroidism (PHPT) is an endocrine disorder of parathyroid glands characterized by excessive secretion of parathyroid hormone (PTH) with an upper normal or elevated blood calcium level. Classical PHPT refers to a symptomatic, multi-system disorder, wich can lead to a significant decrease in the quality of life, disability of patients, and even an increased risk of premature death. Hypercalcemia and the catabolic effect of PTH on various cells are considered as the main pathogenetic mechanisms of the PHPT associated complications. In the last two decades, there has been an increase in the incidence of PHPT, mainly due to the mild forms of the disease, primarily due to the routine calcium screening in North America, Western Europe and, Asia. High prevalence of the disease, as well as the variety of clinical manifestations, cause the attention of different specialists - physicians, rheumatologists, urologists, nephrologists, cardiologists and other doctors. This review cover the main issues of Russian guidelines for the management of PHPT, approved in 2020, including laboratory and instrumental methods, differential diagnosis, surgical and conservative approach, short-term and long-term follow-up. This guidelines also include the recommendations for special groups of patients with hereditary forms of PHPT, parathyroid carcinoma, PHPT during pregnancy.

[Modern problems of hyper- and hypoparathyroidism].

The parathyroid glands are the most important regulators of mineral metabolism. The parathyroid glands were first discovered only in 1880 and their function went the long way unrecognized. Even the term "parathyroid gland" itself speaks of the initial misconception of it as an underdeveloped part of the thyroid. To date, there is a large amount of data regarding the role of this endocrine gland in the human body and the significant changes associated with their dysfunction, including such widespread diseases such primary, secondary and tertiary hyperparathyroidism, hypoparathyroidism. This review covers the problem of the main disturbances in calcium-phosphorus metabolism, presents the results of databases of patients with primary hyperparathyroidism and hypoparathyroidism, as well as current epidemiological trends in Russia and in the world.

[Advanced glycation end products and oxidative stress as a basis for metabolic abnormalities in patients with type 1 diabetes after successful simultaneous pancreas-kidney transplantation].

AIM: To compare advanced glycation end-products (AGE, RAGE) and 3-nitrotyrosine (3-HT) in patients with DM 1 after successful simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). To assess relationship between levels of AGE, RAGE, 3-HT and renal transplant (RT) function, carbohydrate and mineral metabolism. MATERIALS AND METHODS: The study included 58 patients who received kidney transplantation in end-stage renal disease (ESRD). 36 patients received SPK. There were performed routine laboratory, examination of AGE, RAGE, 3-NT, parathyroid hormone (PTH), 25(OH)vitamin D, calcium, phosphorus, FGF23, osteoprotegerin (OPG), and fetuin-A levels. RESULTS: All patients after SPK reached normoglycemia (HbA1c 5.7 [5.3; 6.1] %; C-peptide 3.24 [2.29; 4.40] ng/ml) with the achievement of significant difference vs patients after KTA. Arterial hypertension (AH) was more frequent in recipients of SPK before transplantation than after (p=0.008). AH also persisted in greater number of cases in patients after KTA than after SPK. Patients after SPK had higher AGE (р=0.0003) and lower RAGE (р=0.000003) levels. OPG in patients after SPK was significantly higher (р=0.04). The correlation analysis revealed significant positive correlation between 3-HT and OPG (p0.05; r=0.30), RAGE and eGFR (r=-0.52), HbA1c (r=0.48), duration of AH (r=0.34), AGE with HbA1c (r=0.51). CONCLUSION: The results of the "metabolic memory" markers analysis may indicate their contribution to the persistence of the metabolic consequences of CKD and DM 1 after achievement of normoglycemia and renal function restoration and their possible participation in development of recurrent nephropathy, vascular calcification, and bone disorders.

[Mineral metabolism and COVID-19: is there a connection?]

Due to global spread of COVID-19, the search for new factors that could influence its clinical course becomes highly important. This review summarize the relevant publications on the association between immune system and the main regulators of mineral homeostasis including. In addition, we have highlighted the various aspects of phosphorus-calcium metabolism related to the acute respiratory diseases and in particular to COVID-19. The data about the calcium-phosphorus metabolism in SARS-CoV-2 infection is required to understand the possible clinical implications and to develop new therapeutic and preventive interventions.

[Sporadic primary hyperparathyroidism with multiple parathyroid adenomas].

Multiple lesions of the parathyroid glands (PTG) in primary hyperparathyroidism (PHPT) can be sporadic or develop as part of hereditary syndromes, manifesting at young age. There the description of a severe sporadic PHPT with big parathyroid neoplasms in the young patient is presented. Clinical data made it possible to suspect MEN-1 syndrome or parathyroid carcinomas; however, mutations CDKN, CDC73, MEN1 were excluded. The patient underwent removal of three identified tumors: benign adenomas of the left PTG and hyperplasia of the right one. Postoperative hypocalcemia and severe hungry bone syndrome required the administration of vitamin D and calcium carbonate preparations. However, a year after the operation, a «mild¼ recurrent disease was confirmed. Taking into account the patient's refusal to reoperation and a significant improvement of the target organs state, active observation was continued. The patient needs further careful dynamic monitoring by specialists in order to timely identify indications for repeated surgical treatment to improve the life quality and span.

[Vitamin D metabolite and calcium phosphorus metabolism in in patients with primary hyperparathyroidism on the background of bolus therapy with colecalciferol].

BACKGROUND: Vitamin D (25-hydroxyvitamin D [25(ОН)D]) deficiency (<20 ng/mL) and insufficiency (20-29 ng/mL) are common in primary hyperparathyroidism (PHPT), but data regarding the vitamin D metabolism in this population is limited. AIM: The aim of this study is to estimate the vitamin D metabolites and their relationship with the main parameters of phosphorus-calcium metabolism in patients with PHPT at baseline and on the background of a single dose of cholecalciferol 150,000 IU. MATERIALS AND METHODS: A single-center interventional, dynamic, prospective, comparative study has been carried out. The study included 54 participants, divided into two groups: the 1st group included 27 patients with confirmed PHPT, the 2nd control group (n = 27), matched on gender (p = 0.062). The study included 4 visits; the baseline laboratory examination and a bolus dose of cholecalciferol were performed at the visit 1, the subsequent visits included a dynamic laboratory examination. RESULTS: Vitamin D deficiency (<20 ng/ml) was detected in 69% of patients with PHPT. In the PHPT group (before cholecalciferol therapy), there was a direct association of 1.25(OH)2 D3 with albumin-corrected and ionized calcium, as well as between the 25(OH)D3 /24.25(OH)2 D3 ratio with PTH and magnesium. After taking of cholecalciferol, the levels of 1.25(OH)2 D3 and 25(OH)D3 /24.25(OH)2 D3 were significantly increased, and the levels of 25(OH)D3 /1.25(OH)2 D3 were significantly declined at all visits among patients with PHPT. The common 25(OH)D level was comparable to the control group, however the levels of 1,25(OH)2 D3 in patients with PHPT were 55% higher at baseline, and after taking of cholecalciferol 150,000 IU. They remained increased by 3-7 days by an additional 23-36%, significantly higher than those in the control group: 44%, 74% and 65%, at visits 2, 3 and 4, respectively (p<0.05). The taking of 150,000 IU cholecalciferol in the PHPT group did not lead to a significant increase in hypercalcemia and hypercalciuria, which indicates the safety of this dose in patients with mild hypercalcemia (albumin corrected calcium <3 mmol/l). None of the study participants experienced any side effects. CONCLUSION: The completely comprehensive assessment of vitamin D metabolites was carried out for the first time in patients with PHPT before and after using a bolus dose of cholecalciferol. The results confirmed the differences of vitamin D metabolism in chronic excessive secretion of PTH compared to control group, which is new data in the pathogenesis of the disease, and can be used to develop optimal regimens for cholecalciferol taking in this population.

[Dynamic changes of renin-angiotensin-aldosterone system parameters after surgery of primary hyperparathyroidism].

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.