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The article presents a draft of clinical recommendations for the diagnosis and treatment of primary hyperparathyroidism in adult patients, which provides a modern examination algorithm, discusses the basic principles of laboratory, instrumental diagnostics and treatment approaches.

Phosphaturic mesenchymal tumor can cause osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23), which disrupts the metabolism of phosphate and vitamin D. These tumors are predominantly benign, but less than 5% of them are malignant forms. This article presents the first clinical case in the Russian Federation of a 69-year-old patient with severe hypophosphatemia due to metastatic prostate cancer. Increased secretion of FGF23 are described in the androgen-resistent prostate cancer, which led to pronounced disorders of mineral metabolism, accompanied by a clinical symptom of weakness, pain in the bones, immobilization of the patient. The condition was regarded as worsening against the background of the progression of the disease. However, symptomatic therapy aimed at increasing the level of phosphate significantly improved the patient’s general condition. The medical community should be aware of the possibility of developing hypophosphatemia in patients with weakness and bone pain, which are not always associated with the progression of metastatic prostate cancer.

AIM: To determine significant factors affecting the survival of patients with ectopic ACTH syndrome (EAS).MATERIALS AND METHODS: A multi-center, observational study with a retrospective analysis of patients with EAS. The end point of the study was the fatal outcome of patients from various causes. In order to identify predictors of survival or mortality, univariate and multifactorial Cox regression analyses were carried out. ROC-analysis was used to determine the prognostic threshold values of individual predictors. The survival analysis was carried out using the Kaplan-Mayer method. Statistical data processing was carried out by using IBM SPSS Statistics 23.RESULTS: The age of patients at the time of diagnosis ranged from 12 to 76 years (Me 40 years [28;54]). The age of the studied population was 55 years [38; 64] for women and 42 years [32; 54] for men. The median period of observation was 50 months [13;91], with a maximum follow-up of 382 months. 92 patients (60,9%) had bronchopulmonary NET, 17 (11,3%) — thymic carcinoid, 8 — pancreatic NET, 5 –pheochromocytoma, 1– cecum NET, 1– appendix carcinoid tumor, 1 — medullary thyroid cancer and 26 (17,2%) patients had an occult NET. The primary tumor was removed in 101 patients (66,9%). Bilateral adrenalectomy was performed in 42 (27,8%) cases. Metastases were revealed in 23,2% (n=35) of patients. Relapse of the disease was observed in 24,4%, long-term remission was preserved in 64 patients (74,4%). Death occurred in 42 patients (28%). The average age of survivors was 47,0±15,2 versus 53,5±15,6 years for the deceased (p=0,022). The average survival time from diagnosis for the deceased was 32 months, Me 16,5 months [7;54]. Multivariate analysis revealed that the following factors have a direct impact on survival: age of diagnosis ≥51 years (OR 4,493; 95% CI 2,056–9,818, pCONCLUSION: The prognosis of patients with EAS is influenced by the age of diagnosis, NET localization, distant metastases and level of LNSC. The most common cause of ectopic ACTH syndrome was bronchopulmonary NET which was associated with the best survival rate.

This draft clinical practice guideline for the diagnosis, treatment and prevention of vitamin D deficiency is an update from a previous 2016 document. An analysis of the relevant literature data was carried out, with particular attention to meta-­analyzes, randomized clinical trials and systematic reviews published over the past 5 years. The updated recommendations were discussed and revised by the leading endocrinologists of the Russian Federation, who have expert status in this issue.The classification of 25(OH)D levels has been revised (in particular, the target range of 25(OH)D values has been specified), recommendations have been developed for screening of the disorders associated with vitamin D deficiency. The concept of vitamin D-associated toxicity and recommendations for its diagnosis and prevention have been introduced. Also, indications for the assessment of other vitamin D metabolites besides 25(OH)D, the main marker of vitamin D status, have been indicated.The section regarding treatment of vitamin D deficiency has been expanded and corrected. The major additions concerned the replenishment of the vitamin D deficiency and insufficiency in certain categories of patients (particularly, in the presence of the chronic kidney disease and autoimmune diseases, as well as in pregnant women) and monitoring of the effectiveness and safety of the therapy. The indications for prescribing active metabolites of vitamin D have been adjusted. Recommendations for the prevention of vitamin D deficiency in the general population have also been revised, taking into account large randomized clinical trials, meta-analyzes and systematic reviews of recent years.This publication is an expanded version of the federal guidelines.

BACKGROUND: The Department of Thoracic Surgery of the National Medical Research Center of Surgery named after A. V. Vishnevsky has been dealing with the problem of surgical treatment of patients with neuroendocrine lung tumors for more than 20 years. This article presents the experience of treating patients with ectopic ACTH syndrome over the past 15 years.AIM: To study the features of preparation, surgical aspects of treatment and delayed results in patients with ACTH-producing tumors of bronchopulmonary localization.MATERIALS AND METHODS: The study included 55 patients who underwent surgical treatment of ACTH-producing neuroendocrine tumor of bronchopulmonary localization in the period from 2005 to 2020. In order to systematize the approach to surgical treatment and the choice of the type of operation, a point analysis of the patient’s severity has been developed. Demographic information about patients, anamnesis data, results of hormonal and instrumental studies at pre- and postoperative stages and long-term treatment results were analyzed. The control period of observation of patients after surgery ranged from 6 months to 5 years.RESULTS: The age of the patients ranged from 18 to 72 years (36±15). According to the MSCT results of the chest, neoplasms in the lungs ranging in size from 5 to 25 mm were detected. Patients who scored from 18 to 23 points had lung resection due to the severity of the condition. With a total score from 14 to 18, segmentectomy with lymph node dissection was performed. When the total score was less than 14, a lobectomy with lymph node dissection was performed. During the planned histological examination, lung neuroendocrine tumor of various differentiation degree was confirmed in all patients. The results of treatment were followed in the period from 6 to 60 months, with a median of 19 months [10;24]. Regression of clinical manifestations of hypercortisolism after 1 year of dynamic follow-up period was detected in 83% of patients. After 60 months of follow-up 10 patients (71.4%) had a persistent clinical effect after surgical treatment with complete regression of hypercortisolism symptoms.CONCLUSION: The analysis of the results of surgical treatment, according to the proposed methodological aspects, with dynamic control after 6, 12 and 36 months showed the effectiveness of such surgical intervention with results comparable to the world indicators of leading clinics.

McCune Albright syndrome (MAS) is a rare disorder caused by a sporadic postzygotic mutation in the GNAS gene, which encodes the alpha subunit of the Gs signaling protein.Permanent activation of the Gs protein leads to uncontrolled production of intracellular cAMP, and autonomic hyperfunction of target organs. Estimated prevalence of the disease – 1\100000 to 1\1000000. For the first time, MAS syndrome was described in 1936 as a triad of symptoms – fibrous dysplasia of bones (FD), spots on the skin of the color of «coffee with milk» and premature sexual development. However, it is now known, that the phenotype of the disease is much more complex. This is primarily due to the mosaic type of mutation in the GNAS gene, which determines a wide range of clinical manifestations, and presents certain difficulties in the diagnosis of this syndrome. Various endocrinopathies can be manifestations of MAS like an acromegaly, a hyperthyroidism, Cushing’s syndrome, hypophospatemic osteomalacia as well as damage to other organs and systems, namely the pathology of the gastrointestinal tract, hepato-biliary cardiovascular systems. This article presents three late diagnosed clinical cases of MAS in patients with coffee-milk spots and FD, multinodular goiter; in two cases in combination with acromegaly. We have demonstrated the possibilities of drug therapy for acromegaly in MAS, as well as the experience of using bisphosphonate for the treatment of FD.The knowledge of clinical manifestations of the MAS, early diagnostics and possibilities of drug therapy in the management of these patients have the important prognostic value for improving the quality of patient’s life.

BACKGROUND: Vitamin D (25-hydroxyvitamin D [25(ОН)D]) deficiency (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 (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 (pCONCLUSION: 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.

[English] Due to continuous aging of population and increase in the number of elderly people, osteoporosis became socially significant disease leading to disability, increasing mortality and thereby putting an additional burden on the public healthcare system. Screening to identify groups with a high probability of fracture is recommended using the FRAX® Tool for all postmenopausal women and men over 50 years old (А1). In the presense of major pathological fractures (hip, spine, multiple fractures) it is recommended to diagnose osteoporosis and prescribe treatment regardless of the results of spine and hip double X-ray absorptiometry (DXA) or FRAX® (B2). It is recommended to evaluate C-terminal telopeptide when prescribing antiresorptive therapy and procollagen type 1 N-terminal propeptide (P1NP) when prescribing anabolic therapy to patients receiving osteoporosis treatment at baseline and 3 months after the start of therapy in order to assess the effectiveness of treatment early and adherence to the therapy (А2). It is recommended to diagnose osteoporosis and prescribe treatment to patients with high individual 10-year probability of major pathological fractures (FRAX®) regardless of the results of spine and hip DXA (В3). It is recommended to diagnose osteoporosis and prescribe treatment with a decrease in BMD, measured by DXA, by 2.5 or more T-score standard deviations in femoral neck, and/or in total hip, and/or in lumbar vertebrae, in postmenopausal women and men over 50 years old (А2). It is recommended to prescribe bisphosphonates, denosumab or teriparatide to prevent pathological fractures and increase BMD in patients with postmenopausal osteoporosis, osteoporosis in men, glucocorticoid-induced osteoporosis (А2). When the clinical effect of therapy in osteoporotic patients without pathological fractures is achieved (BMD T-score > -2.0 SD in femoral neck and absence of new fractures), it is recommended to interrupt bisphosphonates therapy for 1-2 years with subsequent follow-up (B2). In patients with vertebral fractures, hip fractures or multiple fractures, it is recommended to continue ceaseless long-term treatment of osteoporosis (В3). All drugs for the treatment of osteoporosis are recommended to be prescribed in combination with calcium and cholecalciferol (А2). In order to reduce the risk of recurrent fractures by prescribing osteoporosis therapy timely and maintaining long-term follow-up of patients over 50 years old with pathological fractures, it is recommended to create Fracture Liaison Services (В2). [Русский] В связи с непрерывным старением населения и увеличением количества лиц старшего и пожилого возраста остеопороз стал социально значимым заболеванием, приводя к инвалидности, повышая уровень смертности и создавая тем самым дополнительную нагрузку на систему здравоохранения. Скрининг для выявления групп с высокой вероятностью переломов рекомендован с использованием Алгоритма FRAX® среди всех женщин в постменопаузе и мужчин старше 50 лет (А1). При наличии патологических переломов крупных костей скелета (бедренной кости, тел(а) позвонков(-а), множественных переломов) в анамнезе рекомендовано устанавливать диагноз остеопороза и назначать лечение независимо от результатов рентгеноденситометрии поясничного отдела позвоночника и проксимального отдела бедренной кости или FRAX® (B2). Рекомендуется определение С-концевого телопептида при назначении антирезорбтивной терапии и исследование уровня N-терминального пропептида проколлагена 1-го типа (P1NP) при назначении анаболической терапии пациентам, получающим лечение остеопороза, исходно и через 3 месяца от начала терапии с целью ранней оценки эффективности лечения и приверженности к терапии (А2). Рекомендовано устанавливать диагноз остеопороза и назначать лечение пациентам c высокой индивидуальной 10-летней вероятностью основных патологических переломов (FRAX®) независимо от показателя рентгеноденситометрии поясничного отдела позвоночника и проксимального отдела бедренной кости (В3). Рекомендовано устанавливать диагноз «остеопороз» и назначать терапию при снижении МПК, измеренной при DXA, на 2,5 и более стандартных отклонения по Т-критерию в шейке бедренной кости, и/или в целом в проксимальном отделе бедренной кости, и/или в поясничных позвонках у женщин в постменопаузе и у мужчин старше 50 лет (А2). Для предупреждения патологических переломов и повышения МПК у пациентов с постменопаузальным остеопорозом, остеопорозом у мужчин, глюкокортикоидным остеопорозом рекомендуется прием бисфосфонатов, деносумаба или терипаратида (А2). Пациентам с остеопорозом без патологических переломов при достижении клинического эффекта терапии (МПК до -2,0 SD по Т-критерию в шейке бедренной кости и отсутствие новых переломов) рекомендовано на 1-2 года прекратить терапию бисфосфонатами с последующим динамическим наблюдением (B2). Пациентам с переломами тел позвонков, бедренной кости или множественными переломами в анамнезе рекомендуется продолжать непрерывное длительное лечение остеопороза (В3). Все препараты для лечения остеопороза рекомендуется назначать в сочетании с препаратами кальция и колекальциферола (А2). С целью своевременного назначения терапии остеопороза и обеспечения длительного наблюдения за пациентами в возрасте 50 лет и старше с патологическими переломами для снижения риска повторных переломов рекомендуется создавать Службы профилактики повторных переломов (В2).

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.

Multiple endocrine neoplasia syndrome type 1 (MEN1, Wermer's syndrome) is a group of heterogeneous inherited diseases, with its pathogenesis related to hyperplasia or neoplasms of several endocrine glands. This syndrome is characterized by autosomal dominant mode of inheritance, high penetrance and similar prevalence among males and females. Prevalence of MEN1 is estimated to be 1:100,000 of the population. An interesting feature of the presented clinical case is a relapse and transformation of pituitary tumor from a prolactin-secreting into the mixed one, with distinct compartments of ACTH- and prolactin-secreting, in a female patient with a family MEN1 syndrome, with involvement of the pancreas, parathyroid and pituitary glands. Her brother had a synchronous manifestation of the same types of tumors, except corticotropinoma. The presented clinical case highlights the necessity of a comprehensive and life-long follow-up of MEN1 patients for a timely detection of neoplasms and appropriate treatment.

Parathyroid carcinoma (PC) is a rare neoplasm with a prevalence of only 0.005 % of all malignancies, and less than 1 % among patients with primary hyperparathyroidism. The diagnosis can be challenging due to the rarity of the disease, similarity of clinical features to parathyroid adenoma, and lack of reliable morphological signs of the tumor. For metastatic cancer of the parathyroid gland does not exist standard drug therapy due to the rare occurrence of this disease. Chemotherapy and radiotherapy failed to show any significant effect on the course of the disease. We report the case of a 27-year old woman with PC previously misdiagnosed as benign thyroid nodule and multiple lung metastases. After the immunohistochemical study and confirm of diagnosis PC the patient was treatment with multikinase inhibitor sorafenib successfully.

A review of the literature is devoted to the issue of secondary hyperparathyroidism (SHPT) with underlying chronic renal failure. Initial manifestations of the disease can be observed even with a minimal decrease in the rate of glomerular filtration and are pathophysiologically associated with violations of normal metabolism of vitamin D with its conversion into D-hormone. SHPT pathogenesis is based on the D-hormone deprivation and triggering of pathophysiology mechanisms of bone remodelling, increased FRP-23, PTH, changes in the serum levels of calcium and phosphorus, which may further lead to significant changes in the bone tissue structure and cardiovascular complications. Active metabolites of vitamin D and vitamin D analogues (Paricalcitol) were developed for the replacement of active forms of vitamin D in conditions of D-hormone deficiency. Due to its chemical structure and pharmacokinetics, Paricalcitol is able to block the synthesis of parathyroid hormone to a greater extent and increase the absorption of calcium and phosphorus in the intestine to a lesser extent, which gives it advantages over pre-existing active metabolites

Myokines are hormone-like acting molecules produced in skeletal muscles during and immediately after exercise. They affect both paracrine (inside the muscles themselves) and endocrine manner (in adipose tissue, liver, endothelium, skin, mucosa etc.) implementing different effects on target tissues, mainly through regulation of metabolic processes (such as glucose and lipid metabolism, growth and division of neurons and endothelial cells and others). The examination of myokines is of great interest for researchers of different medicine departments, particularly for endocrinologists, because of myokines’ involvement in pathogenesis of abdominal and visceral obesity, diabetes mellitus type 2 and cardiovascular diseases that are all the components of metabolic syndrome. The most important issue for clinicians is a possibility of future therapeutic implication of the myokine’s signal pathways in treatment of widespread metabolic disorders.

Представлено краткое изложение клинических рекомендаций по диагностике и лечению остеопороза, разработанных членами Российской ассоциации эндокринологов при участии членов Российской ассоциации по остеопорозу (ревматологов, травматологов, терапевтов, гинекологов-эндокринологов). Рекомендации разработаны с позиций доказательной медицины, в соответствии с требованиями к составлению клинических рекомендаций Минздрава России, опубликованными в 2016 г. Значительное место в изложении отведено диагностике остеопороза у взрослых, дифференциальной диагностике с другими метаболическими заболеваниями скелета, а также принципам патогенетического лечения остеопороза. Клинические рекомендации полезны будут как врачам общей практики, так и специалистам, прежде всего эндокринологам, ревматологам, травматологам-ортопедам, гинекологам, нефрологам, гастроэнднрологам и неврологам, так как остеопороз является мультифакториальным и мультидисциплинарным заболеванием

The review of literature details the issues of genetics, the specific features of inheritance, the clinical picture and treatment of pseudohypoparathyroidisms (PHPT). In practice, clinicians more frequently deal with type 1 PHPT and the diagnosis of this type creates no significant problems. However, despite the low prevalence of the other types of PHPT - 1b, 1c, and 2, the diseases may run with noticeably clinical symptoms and present a significant problem in the context of diagnosis and treatment. This review may be of concern to both clinicians and geneticists who are interested in this problem.В обзоре литературы подробно освещены вопросы генетики, особенностей наследования, клинической картины и лечения заболеваний группы псевдогипопаратиреоза (ПГПТ). В практической деятельности клиницисты чаще имеют дело с типом 1а ПГПТ, и диагностика этого типа не вызывает значительных сложностей. Однако, несмотря на малую распространенность остальных типов ПГПТ - 1b, 1с и 2, заболевания могут протекать с выраженной клинической симптоматикой и представлять значительную проблему в плане диагностики и лечения. Данный обзор может представлять интерес как для клиницистов, так и для генетиков, интересующихся этой проблемой.

The article describes two clinical cases of severe primary hyperparathyroidism (PHPT) caused by parathyroid carcinoma in young female patients who underwent molecular genetic testing to rule out the hereditary forms of PHPT. In both patients, heterozygous germline nonsense mutations of tumor suppressor gene CDC73 encoding parafibromin (p.R91X and p.Q166X) were identified using next-generation sequencing with Ion Torrent Personal Genome Machine (Thermo Fisher Scientific - Life Technologies, USA). It is the first description of CDC73 mutations in Russia, one of the mutations is described for the first time in the world. Identification of germline mutations in the CDC73 gene in patients with PHPT necessitates regular lifelong screening for other manifestations of hyperparathyroidism-jaw tumor syndrome (HPT-JT), PHPT recurrence due to parathyroid carcinoma as well, and identification of mutation carriers among first-degree relatives.Представлено описание двух клинических случаев первичного гиперпаратиреоза (ПГПТ) тяжелого течения у молодых больных раком околощитовидной железы, которым проведено молекулярно-генетическое исследование для исключения наследственных форм ПГПТ. Методом высокопроизводительного параллельного секвенирования на полупроводниковом секвенаторе Ion Torrent Personal Genome Machine (Thermo Fisher Scientific - Life Technologies, США) у обеих пациенток выявлены герминальные гетерозиготные нонсенс-мутации в гене - супрессоре опухолевого роста CDC73, кодирующем белок парафибромин: p.R91X и p.Q166X. В России мутации в указанном гене описываются впервые, одна из мутаций описывается впервые в мире. Выявление герминальных мутаций в гене CDC73 у пациентов с ПГПТ требует пожизненного регулярного профилактического обследования для ранней диагностики компонентов синдрома гиперпаратиреоза с опухолью челюсти (hyperparathyroidism-jaw tumor syndrome - HPT-JT), рецидива ПГПТ после хирургического вмешательства, в том числе вследствие рака околощитовидной железы, а также позволяет выявить носителей мутаций среди родственников первой линии родства.Представлено описание двух клинических случаев первичного гиперпаратиреоза (ПГПТ) тяжелого течения у молодых больных раком околощитовидной железы, которым проведено молекулярно-генетическое исследование для исключения наследственных форм ПГПТ. Методом высокопроизводительного параллельного секвенирования на полупроводниковом секвенаторе Ion Torrent Personal Genome Machine (Thermo Fisher Scientific — Life Technologies, США) у обеих пациенток выявлены герминальные гетерозиготные нонсенс-мутации в гене — супрессоре опухолевого роста CDC73, кодирующем белок парафибромин: p.R91X и p.Q166X. В России мутации в указанном гене описываются впервые, одна из мутаций описывается впервые в мире. Выявление герминальных мутаций в гене CDC73 у пациентов с ПГПТ требует пожизненного регулярного профилактического обследования для ранней диагностики компонентов синдрома гиперпаратиреоза с опухолью челюсти (hyperparathyroidism-jaw tumor syndrome — HPT-JT), рецидива ПГПТ после хирургического вмешательства, в том числе вследствие рака околощитовидной железы, а также позволяет выявить носителей мутаций среди родственников первой линии родства.

Microribonucleic acids (miRNAs) are a class of noncoding RNAs that regulate posttranscriptional gene expression. These molecules are regulators of cell proliferation, metabolism, apoptosis, and differentiation. MiRNAs are not degraded by RNAases and their concentrations can be measured in different body fluids, including serum. The expression of miRNAs varies in intact tissues and tumors, including pituitary adenomas. Pituitary tumors are encountered in 22.5% of the population and, in a number of cases, may be asymptomatic, but in case of invasion or/and hormone overproduction, their clinical presentation is severe with multiple symptoms leading to disability and even death. The mechanisms for the development and progression of pituitary tumors and the markers for remission and recurrence have not been adequately investigated. This literature review discusses the biological significance of miRNAs in pituitary tumors and the potential value of circulating miRNAs as biomarkers.Микрорибонуклеиновые кислоты (микроРНК) - класс некодирующих РНК, которые регулируют посттранскрипционную экспрессию генов. Эти молекулы являются регуляторами, контролирующими пролиферацию, метаболизм, апоптоз и дифференцировку. МикроРНК не подвержены разрушению РНКазами и их концентрация может быть измерена в различных биологических жидкостях, в том числе сыворотке крови. Экспрессия микроРНК в опухолях и здоровых тканях, в том числе в аденомах гипофиза, различна. Опухоли гипофиза встречаются у 22,5% населения и в ряде случаев могут протекать бессимптомно, но при их инвазивном росте и/или гормональной активности новообразования развиваются тяжелые многосимптомные заболевания, приводящие к инвалидности и смерти. Механизмы возникновения и прогрессирования опухолей гипофиза, маркеры ремиссии и рецидива не достаточно изучены. В настоящем обзоре литературы обсуждается биологическое значение микроРНК в опухолях гипофиза и потенциальное значение циркулирующих микроРНК как биологических маркеров.

Clinical symptoms of vitamin D deficiency may be quite misleading and masked as rare hereditary syndromes. We describe a family, sister and brother presented with the pain in lower extremities at the age of 14 and 16years accordingly, with severe vitamin D deficiency that was misdiagnosed in the course of the disease with pseudohypoparathyroidism and 1-alpha-hydroxylase deficiency. They benefited from treatment with alfacalcidol and ossein-hydroxyapatite complex supplement which were further discontinued due to socioeconomic factors. At presentation after 2 years without treatment extremely low 25(OH)D levels were revealed. The patients' family history was remarkable for the same clinical features in mother and her Indian ancestry. Thus we describe an uncommon manifestation of severe vitamin D deficiency in a familial setting which emphasizes the necessity of vitamin D testing in calcium or parathyroid disorders.

This review discusses the recent evidence showing that the skeleton itself produces at least two hormones: fibroblast growth factor 23 (FGF23) and osteocalcin. FGF23 is secreted by osteocytes in bone and acts on the kidney to inhibit 1-alpha-hydroxilation ofvitamin D and promote phosphorous excretion. The affinity of FGF23 to FGF receptor is low, but FGF23 binds to FGF receptor-Klotho complex with more affinity. Therefore, Klotho determines the kidney-specific action of FGF23. Increase in FGF23 or Klotho levels due to genetic defects or ectopic production results in low serum phosphorous levels in humans. Contrary to this, low FGF23 or Klotho levels lead to hypophosphatemia and ectopic calcification. Mouse genetics studies revealed that osteoblast product, osteocalcin, in its undercarboxylated stage acts on the pancreatic beta-cells to enhance insulin production and on peripheral tissues to increase glucose utilization as a result of increased insulin sensitivity and to reduce visceral fat. In addition to this, undercarboxylated osteocalcin may also have another hormonal role, this time as a mediator of testosterone secretion. Osteocalcin was shown to induce testosterone production in Leydig cells of the testes both in ex vivo and in vivo studies. In both localizations, at the pancreas and at the testes osteocalcin acts through the GPCR6A receptor, this activates the cAMP response element-binding protein signaling pathway. Thus, this review reports the recent studies indicating bone ’s role as an endocrine organ.

The article briefly reviews the specific features of target-organ lesions in multiple endocrine neoplasia type 1 (MEN1) syndrome and a clinical case of genetically confirmed MEN1 syndrome in a young female patient. Despite the relative rarity of this disease, timely diagnosis, treatment and screening for its main components are very important for the overall prognosis of patients with MEN1 and their first-degree relatives who are MEN1 gene mutation carriers. The described case is noteworthy for a number of specific features. The authors could find no account of optic chiasm glioma within the framework of MEN1 in the literature. Moreover, therapy-resistant somatoprolactinoma engages attention, which points to its aggressive nature with pituitary adenoma that is not been clearly visualized on magnetic resonance imaging. Of interest is the order of detection of neoplasms, in particular the manifestation of hypoglycemic episodes as a sign of organic hyperinsulinism, which have been initially regarded as epileptic seizures, after the use of sustained-release somatostatin analogues for the treatment of acromegaly.

Objective - to evaluate the value of trabecular bone score and risk factors of fractures in patients with Cushing’s syndrome (CS). Material and methods. One hundred eighty two patients with laboratory-confirmed Cushing’s syndrome were enrolled. All patients underwent measurement of bone mineral density (BMD) at the lumbar spine (LI-LIV), femoral neck and total hip using DXA Prodigy (GEHC Lunar, Madison, WI, USA). Trabecular bone score (TBS) was assessed retrospectively on the basis of already existing DXA images using software TBS iNsight software v2.1 (Medimaps, Merignac, France). Each patient was interviewed for the presence of low-traumatic fractures during the active stage of the disease. A lateral X-ray of the thoracic and lumbar spine ThIV-LV was performed to estimate vertebral fractures. Twenty-four hours urinary free cortisol (24hUFC) was measured by imunochemiluminescence assay VITROS ECi with the preliminary extraction with diethyl ether (reference values 60-413 nmol/24 h). Results. Among 182 patients with CS (149 women, 33 men), Cushing’s disease was confirmed in 151 cases, 9 patients diagnosed with benign adrenal tumor and 22 - ACTH-ectopic syndrome. The median of age - 35 (Q25-Q75 27-49) years, body mass index - 29 (26-33) kg/m2, 24hUFC - 1760 (985-2971) nmol/24h. Fractures were confirmed in 80 (44%) cases, 70 patients suffered from vertebral fractures, which were multiple in 53 cases; 23 patients had non-vertebral fractures. Median of trabecular bone score was 1.205 (1.102-1.307), which is much lower than expected in healthy volunteers (>1.350), while the decrease in bone mineral density (BMD) did not correspond to the severity and prevalence of osteoporosis fractures: LI-LIV Z-score - 1.7 (2.5-0.73); femoral neck Z-score - 1 (-1.6- -0.4). However, when using binary logistic regression analysis (adjusted for sex, age, body mass index, bone mineral density, trabecular bone score and 24hUFC) revealed that the most significant predictor of fracture is high levels of 24hUFC (p=0.001) . The high prevalence of vertebral fractures in patients with CS most likely influenced the results of trabecular bone score and its ability to predict fractures. Conclusion. Patients with active CS have low trabecular bone score, rather than bone mineral density, which reflects deterioration in bone microarchitecture. The low-traumatic fracture occurrence depends on the severity of CS reflected in 24hUFC levels.

В статье представлен обзор современной литературы и результаты наших исследований, обобщающие экспериментальные и клинические данные о влиянии цинакалцета на гормонально-биохимические показатели фосфорно-кальциевого обмена, на маркеры костного метаболизма, минеральную плотность костей, также на гистоморфометрические показатели почечной остеодистрофии у гемодиализных пациентов с вторичным гиперпаратиреозом

The article presents a literature review summarizing the contemporary data on the effects of drug therapy on various parameters of renal osteodystrophy: phosphate binders, vitamin D preparations, bisphosphonates, denosumab, and calcimimetics. We discuss the results of pilot study of the efficacy of teriparatide and denosumab on parameters of bone metabolism in patients with chronic kidney disease.

This study estimates the recovery of bone mineral density (BMD), markers of bone remodeling and quality of life in patients with endogenous Cushing’s syndrome (CS) after 12 months of achieving remission. Materials and methods: 21 patients with CS were prospectively evaluated at active stage of the disease and after being in a full remission (substitutional therapy with hydrocortisone or normal 24 hours urinary free cortisol (24h UFC) and late-night cortisol) during 12 months.A thoracic and lumbar X-ray was performed to reveal vertebral fractures. Bone mineral density (BMD) was measured by DXA ((Prodigy, Lunar, GE, USA). The level of 24h UFC was measured on a VitrosECi. Late-night serum cortisol and markers of bone remodeling were assayed by ECLIA Cobas e601 Roche. Patients fulfilled EQ-5D, ECOS-16 questionnaires and performed "up-and-go ”, "tandem ” and "chair-rising ” tests. Results: Among enrolled patients 17 (80%) were females and 4 (20%) - males; median of age (Q25-Q75) - 41 (33-49) years old; in 10 cases (48%) low traumatic fractures were diagnosed: 7 patients suffered from vertebral fractures; in 3 cases - ribs fractures. After the achieving remission no new fractures were registered and significant improvement in Z-score was reviled at all regions: L1-L4 -1,8 [-2,6; -0.5] at active stage vs -1,2 [-2,2; -0.5] after 12 months of remission (p=0.05); Neck Z-score -0,9 [-1,7; - 0,8] vs -0,7 [-1,6; -0,3], (p=0,003). The level of both bone metabolism markers increased: osteocalcin from 8,2 (6,912,0) to 22,7 (12,1-36,5) ng/ml (p=0,01) and CTx from 0,35 (0,22-0,63) to 0,7(0,28-1,05) ng/ml (p=0,01); whereas 24hUFC decreased from 1449 (926,4-2371) nmol/24h to 66,4(54,2-76,4) nmol/24h (p=0,01). The quality of life significantly improved at all dimensions if measured by ECOS-16. According to the EQ-5D patients suffered less from pain 1,35 (0,49) vs 1,12 (0,34), (p=0,04) and reported the improvement in their health (visual analogue scale) from 49 (18,9) to 68 (10,9), (p=0,004), but did not differ in others dimensions. Although 100% of patients admitted the improvement in their functional ability, the difference in functional tests did not reach statistical significance. Conclusions: Achieving the remission of CS improves BMD and quality of life in patients with CS. However, longer time is needed for full recovery, including the functional performance.

The Wnt/β signaling pathway (Wnt-SP) is a phylogenetically ancient mechanism that regulates development and maintains tissue homeostasis through the control of cell proliferation, differentiation, migration, and apoptosis. The accurate regulation of the canonical Wnt/β-catenin signaling pathway (Wnt-SP) is critical for embryogenesis and postnatal development; and impaired signal transduction at one of its stages leads to various diseases, including organ malformations, cancers, metabolic and neurodegenerative disorders. The literature review discusses the biological role of the canonical Wnt-SP in the development of the skeleton and in the remodeling of bone tissue. The Wnt signal transmission changes observed during genetic mutations cause various human skeletal diseases. Understanding the functional mechanism involved in the development of bone abnormality could open new horizons in the treatment of osteoporosis, by affecting the Wnt-SP. The design of antibodies to sclerostin, a Wnt-SP inhibitor, is most promising now. The paper summarizes the studies that have investigated the canonical Wnt-SP and designed drugs to treat osteoporosis.Сигнальный путь Wnt (СП-Wnt) - филогенетически древний механизм регуляции развития и поддержания гомеостаза тканей за счет контроля пролиферации, дифференциации, миграции и апоптоза клеток. Точность регуляции канонического сигнального пути Wnt/β-катенин (далее в тексте сигнальный путь Wnt - СП-Wnt) имеет решающее значение в эмбриогенезе и постнатальном развитии, а нарушение проведения сигналов на одном из его этапов приводит к различным заболеваниям, включая пороки развития органов, раковые заболевания, метаболические и нейродегенеративные расстройства. Обзор литературы посвящен обсуждению биологической роли канонического СП-Wnt в развитии скелета и ремоделировании костной ткани. Изменения в передаче сигнала Wnt, наблюдаемые при генетических мутациях, вызывают различные заболевания скелета человека. Понимание функциональных механизмов развития патологии костной ткани позволило открыть новые горизонты в лечении остеопороза за счет влияния на СП-Wnt. Наиболее перспективным в настоящее время является разработка антител к склеростину - ингибитору СП-Wnt. Статья обобщает исследования, посвященные каноническому СП-Wnt и разработке лекарственных препаратов для лечения остеопороза.

Постепенное увеличение продолжительности жизни человека, стремление к улучшению ее качества требует улучшения результатов профилактики и лечения остеопороза. Основную часть лиц, подверженных ОП, составляют женщины в менопаузе. Разносторонний подход к проблеме восстановления баланса костного метаболизма привел к внедрению в практику препаратов с различными механизмами действия. В последнее время крайне важным аспектом является повышение приверженности к лечению пациентов, получающих многолетнее лечение остеопороза. Инновационным шагом является внедрение в практику применения нового препарата моноклонального человеческого антитела к лиганду RANK деносумаб. В обзоре представлены результаты сравнительных многоцентровых слепых рандомизированных исследований эффективности деносумаба и пероральных бисфосфонатов. Показано более выраженное достоверно влияние деносумаба (подкожно 60 мг 1 раз в 6 мес.) на прирост МПК во всех отделах скелета (как богатых трабекулярной, так и кортикальной костной тканью), значимое снижение риска переломов при хорошей переносимости лечения.

In this critical review, we have summarized the specific evidence on ibandronic acid (Bonviva) efficacy, tolerability, feasibility and safety acquired from randomized controlled clinical trials, meta-analyses, bridging trials, long-term extension studies, observational studies and clinical experience. We have paid special attention to reviewing the surrogate endpoints, which are routinely used in clinical practice to estimate the treatment efficacy as well as those high technology methods that are currently used in research centers to predict anti-fracture efficacy. Although the only registered indication for Bonviva in Russia is for postmenopausal osteoporosis, we have reviewed the available clinical trials on the efficacy of ibandronic acid to prevent postmenopausal osteoporosis, to treat low bone mass in males, to treat and prevent glucocorticoid induced osteoporosis and other types of secondary osteoporosis and, in particular, in patients after organ transplantation. In addition to this, we have extensively discussed the currently available data on the safety of pharmacologic treatment for osteoporosis.

The objective of this study was to investigate the prevalence of low traumatic fractures, the factors influencing fractures in endogenous Cushing’s syndrome (CS) of various etiologies and their contributions into functional abilities and quality of life in patients with CS. Materials and methods: the retrospective data of patients, who had received treatment due to endogenous CS, (2001-2011), was evaluated. All enrolled patients underwent standard spinal radiographs in lateral positions of the vertebrae Th4-L4. Recent low traumatic non-vertebral fractures were recorded in the medical cards. Bone mineral density (BMD) was measured by DXA GE Lunar Prodigy. Serum samples on octeocalcin (OC), carboxyterminal cross-linked telopeptide of type I collagen (CTx), latenight cortisol in serum were assayed by electrochemiluminescence (ECLIA). 24h urinary free cortisol (24hUFC) was measured by an immunochemiluminescence assay (extraction with diethyl ether). Functional assessment was performed using «chair rising», «up and go» and «tandem» tests. Universal pain assessment tool (verbal descriptor scale, Wong-Baker facial grimace scale, activity tolerance scale), EQ-5D and ECOS-16 questionnaires were given to patients and they self-reported their conditions. Results: Among 215 patients, 178 were females and 37 males, median age 35 (Q25-Q75 27-48); 88patients (40,9%) had low traumatic fractures, including vertebral fractures in 76 cases (in 60 cases multiple vertebral fractures) and non-vertebral fractures in 27 cases (17 patients had rib fractures, 3 -fractures of metatarsal bones, 2 fractures of radius, 2 fractures of tibia and fibula, 1 humerus, 1 breastbone; 1 hip fracture). Patients with fractures had higher 24hUFC, late-night cortisol in serum, lower OC, Total Hip BMD, but did not differ in age, BMI, CTx or etiology of CS. After applying the logistic regression analysis (adjusted for sex, age, BMI, BMD, OC), the main predictor of fractures was late-night serum cortisol level (p=0,001). Patients with late-night serum cortisol higher than 597 nmol/l were more likely to have low traumatic fractures (Odds ratio 2,86 (95%CI 1,55-5,28) p=0,001). Patients with fractures suffered from more pain and reported worse functional abilities. They had slightly worse results in «tandem» test, but did not differ in other functional tests, which assessed mainly muscle power. Conclusions: Patients with CS have very high risk of low traumatic fractures. The severity of hypercortisolemia is the best predictor of low traumatic fractures in patients with CS. Patients with fractures sufferedfrom more severe pain and because of this they restricted their daily activity even more than patients with CS without fractures. Consequently, patients with higher levels of late-night serum cortisol need earlier preventive treatment for osteoporosis.

This review of the literature has been dedicated to experimental and clinical studies of mechanism of action and efficacy of 1—34 amino acid fragment of parathyroid hormone — teriparatide as well as others contries experience of its prescribtion. Teriparatide is an osteoanabolic agent which stimulates bone formation by affecting bone modeling and by stimulating bone remodeling. The effects on modeling lead to increased bone formation whereas the effects on bone remodeling lead to increased bone turnover. Thus, in its mode of action teriparatide differs from all others medicines currently available to treat osteoporosis. Daily subcutaneous injections of teriparatide are proved to be effective to prevent low-traumatic vertebral and non-vertebral fractures in postmenopausal women with the history of vertebral fractures. Teriparatide is effective to treat osteoporosis in male and even more effective than alendronate to treat glucocorticoid-induced osteoporosis. Due to high cost and some restriction related to the duration of therapy (up to 18 months in Russia and 24 months in others countries) teriparatide should be recommended to treat severe osteoporosis in patients with a history >1 moderate clinical vertebral fracture or two or more vertebral fragility fractures or in case the previous treatment was not effective. Teriparatide should be prescribed after bisphosphonates or other antiosteoporotic treatment, but not in the combination with bisphosphonates. The prescribtion of bisphosphonates after teriparatide is effective to maintaine and further improve the effect. Thus, teriparatide is effective to treat severe osteoporosis and osteoporosis resistant to other therapy.

Multiple endocrine neoplasia syndrome type 1 (MEN1, Wermer syndrome) – group o а heterogeneous inherited deseases, caused by hyperlasia or neoplasia of several endocrine glands. The phenotype of MEN1 is broad, and over 20 different combinations of endocrine and non-endocrine metabolic manifestations have been described. This case demonstrates multiple formations of endocrine organs, starting non-classical with macroprolactonoma resistant to dopamine agonists therapy, other endocrine disorders developed gradually eventually: hyperparathyreoidism and hypoglycemia caused by pancreas lesions, produced proinsulin in high levels.