Endocrinology Research Research Articles

Adrenal insufficiency as part of X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative metabolic disease with a frequency 1:17,000 in newborn boys. Being a major part of X-ALD with an incidence of 70-80% of patients, adrenal insufficiency (AI) is alife-threatening condition without timely treatment. The possibility of developing AI during the whole disease duration and the absence of any predictive factor for AI joining shows the necessity of studying AI in X-ALD patients to optimize current diagnostic and treatment algorithms. To study diagnostic and therapeutic features of primary adrenal insufficiency due to X-ALD. A retrospective observational comparative study was conducted in 66 male patients, examined and treated in the Pediatric endocrinology department of Endocrinology Research Centre, Research Centre for Medical Genetics, Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University Detached Structural Unit Russian Children's Clinical Hospital (Moscow, Russia) for 2014-2022. All of patients were diagnosedwith primary AI and a genetically confirmed X-ALD. The median age of X-ALD manifestation was 6.6 years [4.7; 11.1]. The earliest age of AI diagnosis was 1.5 years atthe preclinical stage and 1 year 8 months with clinical symptoms. The renin level was studied in 22.7% at the manifestation of AI (15/66 patients), mineralocorticoid deficiency was found in 7 patients. Family history was positive in 39.4% of patients (n=66), only in 15.1% (10/66 patients) of patients the disease was established at the preclinical stage. In 59.1% (n=66) thecerebral form of the disease (cALD) was established, in 16.6% - adrenomyeloneuropathy (AMN), and in 24.2% - isolated adrenal insufficiency (PAI). Age of AI establishment in the group of patients with AMN (15.6 years) significantly differs from the establishment of AI in patients with cALD (7.4 years, p=0.001) and PAI (5.6 years, p = 0.000). Mineralocorticoid therapy was prescribed simultaneously with glucocorticoid therapy in patients with cALD, in AMN and PAI patients it was added after 11and 7 months, respectively (the differences between AMN and PAI groups were insignificant). Combined hormonal therapy receive 41% of patients with cALD, 54.5% of patients with AMN and 60% of patients with PAI. It is necessary to examine all male patients with AI regardless of the manifestation age to exclude adrenoleukodystrophy, and it is also important to examine patients for the presence of AI regardless of X-ALD manifestation age. The assessment of renin level in the manifestation of AI is also needed toprescribe mineralcorticoid therapy timely. Studying family history is the main method to detect X-ALD at the preclinical stage.

Electrochemical Detection of Hormones Using Nanostructured Electrodes

Hormones regulate several physiological processes in living organisms, and their detection requires accuracy and sensitivity. Recent advances in nanostructured electrodes for the electrochemical detection of hormones are described. Nanostructured electrodes’ high surface area, electrocatalytic activity, and sensitivity make them a strong hormone detection platform. This paper covers nanostructured electrode design and production using MOFs, zeolites, carbon nanotubes, metal nanoparticles, and 2D materials such as TMDs, Mxenes, graphene, and conducting polymers onto electrodes surfaces that have been used to confer distinct characteristics for the purpose of electrochemical hormone detection. The use of aptamers for hormone recognition is producing especially promising results, as is the use of carbon-based nanomaterials in composite electrodes. These materials are optimized for hormone detection, allowing trace-level quantification. Various electrochemical techniques such as SWV, CV, DPV, EIS, and amperometry are reviewed in depth for hormone detection, showing the ability for quick, selective, and quantitative evaluation. We also discuss hormone immobilization on nanostructured electrodes to improve detection stability and specificity. We focus on real-time monitoring and tailored healthcare with nanostructured electrode-based hormone detection in clinical diagnostics, wearable devices, and point-of-care testing. These nanostructured electrode-based assays are useful for endocrinology research and hormone-related disease diagnostics due to their sensitivity, selectivity, and repeatability. We conclude with nanotechnology–microfluidics integration and tiny portable hormone-detection devices. Nanostructured electrodes can improve hormone regulation and healthcare by facilitating early disease diagnosis and customized therapy.

Sexology, sexual development, and hormone treatments in Southern Europe and Latin America, c.1920–40

Displacing the physiological model that had held sway in 19th-century medical thinking, early 20th-century medical scientists working on hormones promoted a new understanding of the body, psychological reactions, and the sexual instinct, arguing that each were fundamentally malleable. Hormones came to be understood as the chemical messengers that regulated an individual's growth and sexual development, and sexologists interested in this area focused primarily on children and adolescents. Hormone research also promoted a view of the body in which ‘hermaphroditism’, homosexuality, and ‘sexual perversions’ such as masochism and sadism were attributed to anomalies in the internal secretions produced by the testes or the ovaries. This article focuses on Spanish, Italian, Argentinian, and Brazilian sexology shaped by endocrinological research in the interwar period. First, it shows the key role hormone treatments played in the historical development of sexology in Southern Europe and Latin America. Second, it looks at how sexologists employed hormone research to study human sexual development in the early stages of life, and how they set about ‘correcting’ what they viewed as ‘sexual anomalies’.

History of establishment and formation of Institute for Reproductive Medicine in the Endocrinology Research Centre

This article presents the historical review of establishment and formation of reproductive medicine department included since 2016 into the Institute for Reproductive Medicine (Endocrinology Research Centre, Moscow, Russian Federation). The basic aim of establishment of the Institute for Reproductive Medicine are coordination between its subdivisions effective treatment and scientific researches among patients with reproductive pathologies and endocrinopathies. The review is supplied with biographical and graphic datas about all leaders of reproductive medical departments from the 1960s until 2020s such as endocrinological gynecology, assisted reproductive technologies, andrology & urology. Authors; group dedicates the present article to scientific supervisors and mentors.

Parathyroid carcinoma case-report in a patient with multinodular goiter and chronic kidney disease: difficulties in diagnosis and treatment (observation from practice)

We would like to present a clinical case of severe primary hyperparathyroidism due to a parathyroid carcinoma of atypical location in a patient with chronic kidney disease of complex etiology and multinodular goiter. Patient S., 59 years old, was followed-up for a long time in tertiary referral hospitals for “chronic tubulointerstitial nephritis with nephrosclerosis”, secondary hyperparathyroidism due to chronic kidney disease (CKD) G3–4, osteoporosis, and a multinodular euthyroid colloid goiter. In July 2021 she was referred to the Endocrinology Research Centre in order to clarify the diagnosis because of the persistence of an extremely high level of parathyroid hormone (PTH) despite cinacalcet treatment. During examination, primary hyperparathyroidism, a left parathyroid gland lesion, multinodular goiter with subclinical thyrotoxicosis, and vitamin D deficiency were diagnosed. After the removal of the left parathyroid gland lesion (histologically confirmed parathyroid carcinoma) and a left-sided hemithyroidectomy, hypocalcemia («hungry bone syndrome») developed, but the level of parathyroid hormone remained elevated. After 3–18 months after surgery, no data for relapse of primary hyperparathyroidism was obtained. The persistent moderate increase in PTH was regarded as secondary hyperparathyroidism in CKD and hypocalcemia. Complex therapy of osteoporosis with the antiresorptive drug denosumab, vitamin D and its active metabolite, calcium preparations, and parathyroidectomy led to a significant increase in bone mineral density (BMD) and no repeated fractures 18 months after surgery.Conclusion. In patients with pre-dialysis CKD and high PTH levels, it is necessary to make a differential diagnosis between primary (PHPT) and secondary hyperparathyroidism (SHPT). Severe manifestations of primary hyperparathyroidism can be suspicious for parathyroid carcinoma.

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

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. To determine the diagnostic value of clinical features of primary PHPT in young patients for predicting the presence of MEN1 gene mutations. 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. 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 «classic» 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%. 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.

Prediction of the development of hypocalcemia in primary hyperparathyroidism patients 1–3 days after radical parathyroidectomy

BACKGROUND: It was impossible to predict the development of hypocalcemia following parathyroidectomy (PTE) in patients with primary hyperparathyroidism (PHPT) until now. Hypocalcemia may be accompanied by myalgia, generalized seizures up to tetany, and arrhythmias. Hypocalcemia following PTE can be prevented by preoperative cholecalciferol supplementation. However, patients with severe hypercalcemia above 3 mmol/L do not receive vitamin D due to the risk of hypercalcemia progression. Despite the existing data showing the safety of cholecalciferol therapy in case of mild elevation of serum calcium, not all patients are prescribed vitamin D supplementation, probably due to the lack of a suitable tool to assess the postoperative hypocalcemia risks.AIM: To design a mathematical model and a software tool for predicting hypocalcemia 1–3 days post-PTE in PHPT patients using the patient’s demographic and clinical data, laboratory test results and preoperative therapy status.MATERIALS AND METHODS: This retrospective study included 478 PHPT patients diagnosed with adenomas and carcinomas of the parathyroid gland (PTG) who underwent radical PTE between 1993–2010 or 2018–2020 at the Endocrinology Research Centre. The following parameters were analyzed: sex; age; laboratory markers prior to calcimimetic and antiresorptive therapy: PTH, total calcium, phosphorus; osteocalcin (OC), alkaline phosphatase (ALP), C-terminal telopeptide of type 1 collagen. Also we analyzed 25-hydroxyvitamin D (25(OH)D); bone mineral density (BMD) measured by X-ray densitometry; medical history of low-energy fractures; preoperative therapy with denosumab, bisphosphonates, cinacalcet, cholecalciferol. Categorical gradient boosting (CatBoost) was built to predict the risk of postoperative hypocalcemia.RESULTS: The prevalence of severe osteoporosis is higher in the postoperative hypocalcemia group compared to the nonhypocalcemia group (27% vs. 15%), wherein the frequency of preoperative administration of cholecalciferol in this group is lower (8% vs. 25%). A CatBoost model was built to predict postoperative hypocalcemia using 13 predictors (sex, age, PTH, serum total calcium, phosphorus, OC, BMD reduction, 25(OH)D, administration of cholecalciferol, bisphosphonates, denosumab, and cinacalcet. The proposed model http://194.87.111.169/hypocalcemia for post-PTE hypocalcemia in PHPT patients achieved the following metrics: positive predictive value 73.3%-86.7%; negative predictive value 74.9%-89.3%.CONCLUSION: The model can be used to choose the appropriate preand postoperative approaches for patients who undergo rPTE.

Primary hyperparathyroidism in children

Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) with upper-normal or elevated blood calcium levels due to primary thyroid gland pathology. PHPT is a rare pathology in children, with a prevalence of 2-5:100,000 children according to the literature. Due to the non-specificity of clinical manifestations at onset (nausea, vomiting, abdominal pain, emotional lability), the disease may remain undiagnosed for a long time. To study the features of the course and molecular genetic basis of primary hyperparathyroidism in children. Retrospective observational study of 49 patients diagnosed with primary hyperparathyroidism. All patients underwent a comprehensive laboratory-instrumental and molecular genetic study at the Institute of Pediatric Endocrinology, Endocrinology Research Center of Russia in the period 2014-2022. The first clinical symptoms of PHPT were noted at the age of 13.8 years [10.6; 1 5.2], among which fatigue, headaches, dyspepsia, lower limb pain, and fractures were the most common. The age of diagnosis was 15.81 years [13.1; 16.8], all children were found to have high levels of PTH, total and ionized calcium, with hypophosphatemia in 93.9% of patients (n=46) and hypercalciuria in 43% (n=21). Five out of 49 patients (10.2%) were found to have ectopy of the thyroid: 3 showed an intrathyroidal location, 2 in the mediastinal region. Molecular genetic study revealed mutations in 32.7% of patients (n=16, CI (21; 47)), mutations inMEN1being the most frequent (n=11). Pathogenic variants inCDC73were detected in 3patients,RET -in 2. Among the operated 39 patients, adenoma of the thyroid was detected in 84.6% of cases (n=33), hyperplasia in 7.7% (n=3), atypical adenoma in 5.1% (n=2), carcinoma in 5.1% of cases (n=2). The paper presents the peculiarities of the course and the results of molecular genetic study of pediatric PHPT. This sample is the largest among those published in the Russian Federation.

THU425 Brief, Low-impact, High-intensity Osteogenic Loading Training Utilizing Proprietary Osteostrong Devices With Once-A-Week, 10 Minute Treatments Improves Bone Mineral Density In Women With Osteoporosis Of The Lumbar Spine

Abstract Disclosure: N. Papadopoulou-Marketou: None. A. Papageorgiou: None. G. Vavetsis: None. T. Panagiotis: None. G.P. Chrousos: None. Introduction: Osteoporosis is a chronic condition characterized by a decrease in bone density and deterioration of microarchitecture. It has been associated with a high bone-fracture risk, an increased mortality, and vast health-care costs. Pharmaceutical treatment along with resistance exercise are usually prescribed. “Osteostrong” is a type of bone strengthening that uses brief (12 min), weekly, low-impact, high-intensity osteogenic loading. Aim: to investigate the therapeutic impact of Osteostrong in people with osteoporosis. Methods: In total, 140 postmenopausal women with osteoporosis of the lumbar spine, followed at the Unit on Clinical and Translational Research in Endocrinology, University of Athens, Athens, Greece, were enrolled. They were divided into 2 groups. Group A (GA) included 70 women who were treated with Osteostrong (mean age: 57,7 y, 95% CI 54, 9-60,6 y); Group B (GB) included 70 women who had no exercise intervention (mean age 59,2 y, 95% CI 55,6-61,9 y). All the participants had a complete physical examination, an assessment for exclusion of secondary osteoporosis, bone markers CTX1 and PINP, and a DXA examination [Horizon W (S/N 300472M], twice, at the time of inclusion in the trial, at 9 and 12 months after onset of intervention. Preliminary data at 9 months are shown. Statistical analysis, Medcalc version 20.2. Results: Paired Student t-test (chi-squared) of Bone Mass Density (BMD) and T-score before (1) and after intervention (2) in GA and GB showed: BMD lumbar spine (L1-L4) and T-score L1-L4: GA1 (mean:0.815), GA2 (mean:0.833) (p<0.0007) and GA1 (mean: −2.27), GA2 (mean: −1.93) (p<0.0001)/ GB1 (mean: 0.852), GB2 (mean: 0.851) (p=0.93) and GB1 (mean: −1.98), GB2 (mean: −1.80) (p=0.054), respectively. Trabecular bone score (TBS) and T-score TBS: GA1 (mean: 1.217), GA2 (mean: 1.238), (p=0.036) and GA1 (mean: −2.76), GA2 (mean: −2.52), (p=0.045)/ GB1 (mean:1.22), GB2 (mean: 1.204) (p=0.14) and GB1 (mean: −2.75), GB2 (mean: −2.85), (p= 0.560), respectively. The CTX1 and PINP values were within normal reference range at 9 months. Discussion: The study showed a statistically significant improvement of BMD in the lumbar spine and TBS in people with osteoporosis treated with Osteostrong. The Osteostrong method may have a synergistic effect with anti-osteoporotic medication, significantly reducing bone fracture risk. Conservative therapeutic interventions are important challenges to minimize the osteoporosis-related poor quality of life and mortality. Presentation: Thursday, June 15, 2023

Long-term results of corrective surgical interventions in patients with diabetic midfoot neuroosteoarthropathy

BACKGROUND: Diabetic neuroosteoarthropathy is a disabling complication of diabetes mellitus that develops as a result of impaired peripheral innervation and characterized by damage to bones and joints of non-infectious origin. As a result of pathological bone fractures, gross deformities of the foot are formed, which entails development of chronic ulcerative defects in areas of excessive load pressure. Currently, a number of surgical interventions are used to correct deformities, such as resection of bone structures, correction with metal structures and external fixation devices, but there is practically no data on their long-term results in the domestic literature.AIM: To study the results of orthopedic corrective interventions in patients with diabetes mellitus and midfoot neuroosteoarthropathy.MATERIALS AND METHODS: An analysis was made the data collected by questionnaire method of 55 patients operated in the diabetic foot department in the Endocrinology research centre from 2009-2019. All patients underwent a reconstructive operation aimed correcting a gross deformity of the midfoot. In postoperative period, the affected limb was off-loaded by total contact cast for a period of 3-6 months, and in the future, complex orthopedic shoes for permanent use and regular podiatric care were recommended to patients.RESULTS: After the first surgical intervention, 16 patients developed a recurrence of deformity, which required a second surgical intervention. The median period between interventions was 3 years. Chronic wounds of various localization of the operated foot were found in 25 patients.The median period between surgery and ulcer formation was 5 years. 9 patients with chronic wounds underwent minor amputations at the same foot. Amputations on the contralateral limb were performed in 7 patients. None of the patients underwent major amputations.CONCLUSION: Charcot foot is a severe complication of diabetes mellitus that can lead to loss of a lower limb. Due to results of the research orthopedic corrections of the midfoot deformities in patients with DNOAP can reduce the risk of ulcer developement and possible major amputations. Active monitoring and adequate orthopedic care in the postoperative period significantly reduce the risk of deformity recurrence and the need for repeated surgical interventions.

Investigation of neural network models application in EU-TIRADS thyroid nodules classification for personalization of thyroid gland ultrasound diagnostic

SUBSTANTIATION. It is known that about 69% of all thyroid nodules undergoing surgical treatment are benign formations, and up to 75% of patients with an intermediate cytological conclusion undergo unnecessary surgical intervention. This suggests that improving the quality of differential diagnosis of nodular formations will avoid excessive economic costs for the healthcare system. In this regard, AI technologies in diagnostic algorithms for the classification of thyroid nodules were involved.AIM. Improving the efficiency of automatic classification of thyroid nodules on ultrasound images by using a set of neural network models.MATERIALS AND METHODS. We used ultrasound images of thyroid nodules available in open sources and obtained with the help of 3 ultrasound devices of Endocrinology Research Centre as part of Project № 22-15-00135 of the grant of the Russian Science Foundation. This article check the hypothesis that the size of the training set cannot be increased by repeating similar images from the ultrasound cine loop of one patient, but only by expanding the dataset with new unique specimens of other patients and/or data from the augmentation process.RESULTS. As a result, a neural network model EfficientNet-B6 was proposed to solve the problem of EU-TIRADS classification of thyroid nodules based on ultrasound images of the thyroid gland.CONCLUSION. The results obtained allow us to advance in the use of artificial intelligence methods for personalized medicine in thyroid diseases.

Metastatic lesions of the adrenal glands. The experience of Endocrinology Research Center.

Differentiation between benign, primary and secondary malignant tumors is a critical problem in the clinical treatment of adrenal tumors, especially in patients with isolated adrenal lesions. In most cases, the correct diagnosis can be established microscopically with standard staining with hematoxylin and eosin. However, there are cases when it is almost impossible to distinguish metastasis from primary adrenal cancer, so an accurate diagnosis requires an immunohistochemical examination.This article presents five unique observations of secondary adrenal tumors that were diagnosed by us in the current surgical material: metastasis of clear cell renal cell carcinoma, follicular variant of papillary thyroid cancer, metastasis of keratinizing squamous cell carcinoma of the cervix, lymphoepithelioma-like carcinoma of the bladder, as well as malignant mesothelioma. Taking into account the extreme rarity of the presented observations, we present an analysis of the literature data.

Effect of components of the renin-angiotensin system, rs2106809 polymorphism of the ACE2 gene, and therapy with RAS blockers on the severity of COVID-19

Angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS), providing counter-regulation of its effects and, simultaneously, a receptor for the SARS-CoV-2 entering. It is suggested that factors regulating the balance of the major components of RAS, including ACE2 gene polymorphism, therapy with RAS blockers (ACE inhibitors and angiotensin receptor blockers) - may affect the severity of COVID-19. The aim of the study was to investigate the effect of RAS components, the relationship of ACE2 gene polymorphism rs2106809 and ACEi/ARBs therapy with the COVID-19 severity. The study included patients with COVID-19 hospitalized in Endocrinology research centre (n = 173), who were divided into groups of moderate and severe course. Determination of RAS components was performed by ELISA, identification of polymorphism by PCR. Statistical analysis was performed using nonparametric statistical methods; differences in the distribution of genotype frequencies were assessed using Fisher's exact test χ2. The groups differed significantly in age, blood glucose levels, and inflammatory markers: leukocytes, neutrophils, IL-6, D-dimer, C-reactive protein, ferritin and liver enzymes, which correlated with the severity of the disease. When comparing patients in terms of ACE, ACE2, angiotensin II, ADAM17 there were no statistically significant differences between the groups (p=0.544, p=0.054, p=0.836, p=1.0, respectively), including the distribution by gender (in men: p=0.695, p=0.726, p=0.824, p=0.512; in women: p=0.873, p=0.196, p=0.150, p=0.937). Analysis of the distribution of AA, AG, and GG genotypes of the rs2106809 polymorphism of the ACE2 gene also revealed no differences between patients: χ2 1.35, p=0.071 in men, χ2 5.28, p=0.244 in women. There were no significant differences in the use of RAS blockers between groups with different course severity: χ2 0.208, p=0.648 for ACEi, χ2 1.15, p=0.283 for ARBs. In our study, the influence of activation of RAS components (ACE, ACE2, AT II, ADAM17) and ACE2 gene polymorphism on the severity of COVID-19 course was not confirmed. The severity of COVID-19 course correlated with the level of standard inflammatory markers, indicating the general principles of the infection as a systemic inflammation, regardless of the genetic and functional status of the RAS.

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

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. 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). 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). 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.

Epinephrine Affects Ribosomes, Cell Division, and Catabolic Processes in Micrococcus luteus Skin Strain C01: Revelation of the Conditionally Extensive Hormone Effect Using Orbitrap Mass Spectrometry and Proteomic Analysis.

In the current study, extensive Orbitrap mass spectrometry analysis was conducted for skin strain Micrococcus luteus C01 planktonic cultures and biofilms after 24 h and 72 h of incubation either in the presence of epinephrine or without any implementations. The investigation revealed the complex and conditionally extensive effect of epinephrine at concentrations closer to normal blood plasma concentrations on both planktonic cultures and biofilms of skin strain M. luteus C01. The concentrations of hundreds of proteins changed during the shift from planktonic growth mode to biofilm and hundreds of proteins were downregulated or upregulated in the presence of epinephrine. Ribosomal, TCA, and cell division proteins appear to be the most altered in their amounts in the presence of the hormone. Potentially, the regulatory mechanism of this process is connected with c-di-GMP and histidine kinases, which were affected by epinephrine in different samples. The phenomenon of epinephrine-based biofilm regulation in M. luteus C01 has wide implications for microbial endocrinology and other research areas.

Insulinoma: analysis of prevalence and incidence in the world

BACKGROUND: Currently, there are no data on the prevalence and incidence of insulinoma in Russia. The published world data on the epidemiology of the tumor are largely variable. Thus, it is important to systematize information on the prevalence and incidence of insulinoma in the world, including in Russia. AIM: To assess the prevalence and incidence of insulinoma in the world.TASKS Analysis of literature data.Analysis of the database of the Endocrinology Research Centre.MATERIALS AND METHODS: To implement Task 1, an analysis of foreign and Russian articles published in the PubMed and eLIBRARY.RU databases from 1927 was carried out until June 1, 2023, including the following keywords: «Insulinoma», «Epidemiology», «Frequency», «Incidence», «Nationwide», «Database». Based on the obtained results, an analysis of the prevalence and incidence of insulinoma in the world and in Russia was made. To implement Task 2, the analysis of patient records and the electronic database of the Endocrinology Research Centre was carried out.RESULTS: Based on data in individual countries the prevalence and incidence of insulinoma for the world population amounted to: an average of 16.4 per 1 million population and 0.9 per 1 million population per year, respectively. If extrapolating the world data, the number of patients with insulinoma in Russia can be 1066–2362 and 72–173 new cases are diagnosed annually (11.9 per 1 million population and 0.9 per 1 million population per year, respectively). The largest number of patients with insulinoma in Russia was recorded in the Endocrinology Research Centre and amounted to 275 cases for the period 2006–2022.CONCLUSION: In the Russian Federation, it is important to create a register of patients with insulinoma on the basis of the existing electronic database of the Endocrinology Research Centre in order to obtain accurate information about the current needs of patients with insulinoma in medical care and drug provision, as well as to conduct full-fledged scientific research.

Global trend of research and publications in endocrinology, diabetes, and metabolism: 1996–2021

Global trend of research and publications in endocrinology, diabetes, and metabolism: 1996–2021

Diabetes mellitus associated with type A insulin resistance

Insulin resistance type A is a monogenic disorder with insulin action defect, observed in females with acanthosis nigricans (AN), hyperandrogenism, hyperinsulinemia, insulin resistance (IR) without obesity. We present a family case of diabetes mellitus (DM) with IR in two sisters with obesity and positive family history of DM in three generations. Hyperglycemia was identified at the age of 13 in the older sister and at 11 in the younger sister after COVID-19. Type 2 diabetes (DM2) was diagnosed in mother in the same time with children. Maternal grandmother was diagnosed with DM2 in 58 years old. Patients were examined in 6 months after diagnosis hyperglycemia in Endocrinology Research Centre. The older sister had obesity, AN, and striae distensae. Glycosylated hemoglobin (HbA1c) 6.2%. Impaired glucose tolerance (IGT), hyperinsulinemia and IR, hyperandrogenism, non-alcoholic fatty liver disease (NAFLD), arterial hypertension were diagnosed. The younger sister had obesity, striae distensae. HbA1c — 6.0%. Impaired fasting glucose (IFG), IGT, hyperinsulinemia, IR, NAFLD were diagnosed. Antibodies (AAb) to ZnT8A, IA2, GAD absented in both sisters. A genetic test was provided, a heterozygous mutation in the INSR gene p.V167M was identified in both sisters, mother and grandmother. IR type A was identified in a family with the phenotype of DM2 in this case. This case demonstrated that children with carbohydrate metabolism disorders and obesity without Islet cell autoantibodies have to reffered for a genetic testing. Disordered carbohydrate metabolism was diagnosed in the same time after a COVID-19 in three family members who did not previously have disordered carbohydrate metabolism. We suppose that SARS-CoV-2 can be a trigger for the development of carbohydrate metabolism disorders in IR type A.

The Russian registry of primary hyperparathyroidism, latest update.

Until recently no major epidemiological research of primary hyperparathyroidism (PHPT) has been conducted in the Russian Federation, this led to the creation of the Russian online registry. The objective of this study is to estimate the clinical and biochemical profile, classical and non-classical complications, surgical intervention and medical therapy of the patients with different forms of PHPT in the Russian Federation. The cross-sectional, observational, continuous study was conducted at the Endocrinology Research Centre (Moscow). The present study explored retrospective data from 6003 patients submitted to the Registry between 12.12.2016 and 25.10.2022 from 81 regions of the Russian Federation (http://pgpt.clin-reg.ru/). The median age was 59 [60; 66] years with a female:male ratio of 11.7:1. Symptomatic PHPT was observed in 74.3% while asymptomatic form - only in 25.7% of cases. Bone pathology was the predominant clinical manifestation in 62.5% of cases (n=2293), mostly in combination with visceral complications 45.7% (n=1676). The majority of patients (63.3%) had combined visceral disorders including kidney damage in 51.8% and gastroduodenal erosions/ulcers in 32.3% of patients. Symptomatic patients were older (60 [53; 67] vs. 54 [45; 62] years, p<0.001) and had more severe biochemical alterations of calcium-phosphorus metabolism. Cardiovascular disease (СVD) was recorded in 48% of patients, among them the most frequent was arterial hypertension (up to 93.9%). A genetic test was conducted in 183 cases (suspicious for hereditary PHPT) revealing the mutations in MEN1, CDC73, RET genes in 107, 6 and 2 cases, respectively. Surgery was performed in 53.4% of patients with remission achievement in 87%, the relapse/persistence were recorded in 13% of cases. Histological examination revealed carcinoma in 4%, atypical adenoma in 2%, adenoma in 84% and hyperplasia in 11% of cases. Drug therapy was prescribed in 54.0% of cases, most often cholecalciferol. The detection rate of PHPT has increased in the Russian Federation in recent years. This increase is associated with the start of online registration. However, the majority of patients remain symptomatic with significant alterations of phosphorus-calcium metabolism that indicates delayed diagnosis and requires further modifications of medical care.

Features of aging replicative and biochemical aspects among females with non-iatrogenic hypergonadotropic hypogonadism

Estrogenic deficiency is the basic condition of human ageing that leads to hypergonadotropic hypogonadism. The existence of correlation between hypergonadotropic hypogonadism, replicative (leukocyte telomere length) and biochemical data is widely supposed among females with physiological (menopausal) and pathological (primary ovarian insufficiency) estrogenic deficiency is not unreasonable. To evaluate features of replicative (telomere length) and biochemical (metabolic syndrome) ageing markers among females with physiological (menopausal) and pathological (primary ovarian insufficiency) estrogenic deficiency. Research has been provided in collaboration between Endocrinology Research Centre of the Russian Ministry of Health and Lomonosov Moscow State University Medical Research and Educational Centre in the period since 10.01.2021 until 01.08.2022.110 females (20-75y.o.) have participated in the present research.Group 1: 26 females receiving menopausal hormonal therapy (MHT) ≥ 5 years with 0,5; 1; 2 mg estrogenic component.Group 2: 27 females in physiological menopause without MHTGroup 3: 33 females with primary ovarian insufficiency and receiving sex-steroid replacement therapy.Group 4: 24 healthy reproductive age females without sex-steroid replacement therapy.Patients have undergone laboratory genetic (leucocyte telomere length), biochemical analyses.DNA extraction - with Qiagen DNA blood mini kit (Germany). Biological material was cito conserved with Ficoll solution. Leukocyte telomere length - with real-time polymerase chain reaction PCR (Flow-fish).Soft program IBM SPSS Statistics (version 26,0 for Windows) has been used for statical analysis. 1.Menopausal females receiving MHT were inclined to highest HDL-P levels (p&lt;0,006).2.Females with primary ovarian insufficiency were inclined to relatively highest serum creatinine level (p&lt;0,001).3.Reproductive age females had relatively highest telomere length (p&lt;0,001).4.FSH level correlates negatively and moderately (ρ= - 0,434) leukocyte telomere length (р&lt;0,001) among females. Females with premature ovarian insufficiency are most sensible to ageing due to features of replicative and biochemical markers.