A summary of the Russian clinical guidelines on the diagnosis and treatment of osteoporosis.

Key statements of the Russian clinical guidelines on the diagnosis and treatment of osteoporosis are summarized. They were developed by a task force representing the key Russian professional associations involved in the management of osteoporosis and approved by the Russian Ministry of Health. PURPOSE: To summarize key statements of the Russian clinical practice guidelines for the diagnosis and treatment of osteoporosis. METHODS: The Russian clinical guidelines on the diagnosis and treatment of osteoporosis were developed by a task force representing the key Russian professional associations involved in the management of osteoporosis: These comprised the Russian Association of Endocrinologists, the Russian Association for Osteoporosis, the Association of Rheumatologists of Russia, the Association of Orthopedic surgeons and Traumatologists of Russia, the Russian Association of Gynecologists-Endocrinologists, and the Russian Association of Gerontologists and Geriatrics. The guidelines are based on a systematic literature review and principles of evidence-based medicine and were compiled in accordance with the requirements for clinical recommendations developed by the Ministry of Health of the Russian Federation. RESULTS: Key statements included in the Russian guidelines of osteoporosis approved by the Russian Ministry of Health in 2021 are summarized. The statements are graded based on levels of evidence and supported by short comments. The guidelines are focused on the current approach to screening, diagnosis, differential diagnosis, and treatment of osteoporosis. CONCLUSION: These guidelines are a practical tool for general practitioners, as well as medical specialists, primarily endocrinologists, rheumatologists, orthopedic surgeons, and other physicians who are involved in the management of patients with osteoporosis.

Serum Vitamin D Metabolites by HPLC-MS/MS Combined with Differential Ion Mobility Spectrometry: Aspects of Sample Preparation without Derivatization.

In current clinical practice, a thorough understanding of vitamin D metabolism is in high demand both for patients with various diseases and for healthy individuals. Analytical techniques that provide simultaneous measurement of multiple metabolites are preferred. Herein, the development of an HPLC-DMS-MS/MS method for the quantitation of vitamin D compounds (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3, 24,25(OH)2D3, and D3) in serum is described. The selected sample preparation procedure based on the combination of liquid-liquid and solid-phase extraction, which excluded a lengthy derivatization step, was compared with other common approaches. Sensitivity was increased through the implementation of differential ion mobility separation. The proposed assay allowed us to determine the low abundant 1,25(OH)2D3 with the detection limit of 10 pg/mL. The validation study showed good linearity (r2 > 0.99), a wide analytical range (2.5-75 ng/mL for 25(OH)D3), and acceptable precision (<7%) for all metabolites. The recovery ranged from 71% to 93% and the matrix effect from 0.80 to 0.95 depending on the metabolite; accuracy determination was performed using DEQAS controls.

Three-year progress report of Bone Health TeleECHO Moscow: a strategy to improve the care of patients with osteoporosis and other metabolic skeletal diseases in underserved communities of Russia.

Bone Health TeleECHO Moscow is the first Russian-speaking Project ECHO (Extension for Community Healthcare Outcomes) program that is modeled after the original Bone Health TeleECHO created in the USA. Bone Health TeleECHO Moscow was effective (effect size of 0.87 p < 0.001) at improving clinicians' skills in the management of osteoporosis based on self-evaluation over 3 years. INTRODUCTION: Bone Health TeleECHO (Extension for Community Healthcare Outcomes) Moscow is the first Russian-speaking ECHO program, modeled after Bone Health TeleECHO at the University of New Mexico, USA. The bone ECHO programs are designed to expand the capacity to deliver best practice skeletal healthcare worldwide through ongoing technology-enabled case-based collaborative learning. To evaluate the impact of the first 3 years of Bone Health TeleECHO Moscow on physicians' knowledge in the management of bone diseases. METHODS: Demographic data were obtained, and outcomes were assessed through an electronic blinded self-efficacy questionnaire focusing on competence and skills in 20 domains of osteoporosis care before and after each year of participation in the Bone Health TeleECHO Moscow. RESULTS: Over 3 years, a total of 296 participants completed the questionnaire. Average attendance for each monthly session increased from 64 in 2019 to 73 in 2020 and to 96 in 2021. Participants were from all regions of Russia and Russian-speaking countries. The mean age of respondents was 43 years with the youngest being 23 and the eldest 74. The most common participants' primary specialties were endocrinology (n = 263), gynecology (n = 20), orthopedics (n = 3), and other (n = 10). All of our participants were physicians, including 73 MD PhDs. This educational intervention was associated with a statistically significant improvement in each of the 20 domains of osteoporosis care, with an effect size of 0.87 (p < 0.001). CONCLUSION: Bone Health TeleECHO is effective at improving clinicians' skills in the management of osteoporosis based on self-evaluation over 3 years.

Prediction of recurrence and remission within 3 years in patients with Cushing disease after successful transnasal adenomectomy.

BACKGROUND: Some laboratory and clinical features are associated with a probability of recurrence after transnasal adenomectomy for Cushing disease (CD). However, there is no consensus on a set of predictors. Rules for prediction of recurrence were not proposed earlier. AIM: To develop prediction model of recurrence/remission after successful neurosurgical treatment for CD. METHODS: Retrospective single-site comparative study included 349 patients (52 men and 297 women) with a verified diagnosis of CD who underwent effective endoscopic transsphenoidal adenomectomy between 2007 and 2014. Clinical and laboratory parameters were evaluated. Laboratory tests were performed using immunochemiluminescent method. Time-to-event analysis and ROC-analysis were applied. Multivariate models were developed using logistic regression and artificial neural network (ANN). RESULTS: Postoperative cortisol and ACTH levels and their combinations cannot be used for prediction of recurrence. ANN for prediction of recurrence within 3 years after successful surgery was developed. Input variables are age, duration of the disease, MRI data on adenoma, morning postoperative levels of ACTH and cortisol, output variable is binary (recurrence/remission). Predictive value for remission is 93%, 95% CI [89%; 96%], and predictive value for recurrence is 85%, 95% CI [71%; 94%]. Web-calculator based on the model is developed and free for use. CONCLUSION: Effective method for prediction of recurrence and long-term remission within 3 years after successful endoscopic transsphenoidal adenomectomy is proposed.

Bone Health TeleECHO: a Force Multiplier to Improve the Care of Skeletal Diseases in Underserved Communities.

PURPOSE OF REVIEW: This review describes the global development of a model of technology-enabled collaborative learning for healthcare professionals called Project ECHO (Extension for Community Healthcare Outcomes) and its applications for the management of patients with skeletal diseases. RECENT FINDINGS: The prototype Bone Health TeleECHO was established in 2015, with others now operational in the USA and other countries, and more expected to follow soon. Each teleECHO program, in the right language and convenient time zone, provides a virtual community of practice for healthcare professionals to benefit from real-time interactive case-based learning and brief didactic presentations on topics of interest. Bone Health TeleECHO elevates the level of knowledge of participants and improves self-confidence in managing patients with skeletal diseases. The development of many teleECHO programs worldwide serves as a force multiplier, with the potential to narrow the osteoporosis treatment gap and enhance the effectiveness of fracture liaison services.

Genetic and Epigenetic Aspects of Type 1 Diabetes Mellitus: Modern View on the Problem.

Omics technologies accumulated an enormous amount of data that advanced knowledge about the molecular pathogenesis of type 1 diabetes mellitus and identified a number of fundamental problems focused on the transition to personalized diabetology in the future. Among them, the most significant are the following: (1) clinical and genetic heterogeneity of type 1 diabetes mellitus; (2) the prognostic significance of DNA markers beyond the HLA genes; (3) assessment of the contribution of a large number of DNA markers to the polygenic risk of disease progress; (4) the existence of ethnic population differences in the distribution of frequencies of risk alleles and genotypes; (5) the infancy of epigenetic research into type 1 diabetes mellitus. Disclosure of these issues is one of the priorities of fundamental diabetology and practical healthcare. The purpose of this review is the systemization of the results of modern molecular genetic, transcriptomic, and epigenetic investigations of type 1 diabetes mellitus in general, as well as its individual forms. The paper summarizes data on the role of risk HLA haplotypes and a number of other candidate genes and loci, identified through genome-wide association studies, in the development of this disease and in alterations in T cell signaling. In addition, this review assesses the contribution of differential DNA methylation and the role of microRNAs in the formation of the molecular pathogenesis of type 1 diabetes mellitus, as well as discusses the most currently central trends in the context of early diagnosis of type 1 diabetes mellitus.

Clinical significance of TSH circadian variability in patients with hypothyroidism.

OBJECTIVE: To investigate the clinical significance of thyroid-stimulating hormone (TSH) circadian variability in patients with hypothyroidism. DESIGN: A total of 20 women with subclinical hypothyroidism and 22 patients taking L-thyroxine replacement therapy for hypothyroidism were enrolled in the study. Measurements of serum TSH levels were done twice a day from 08.00 to 09.00 a.m. and from 2.00 to 4.00 p.m. RESULTS: The morning median TSH value in the patients with subclinical hypothyroidism was 5.83 mU/L; in the afternoon, it was 3.79 mU/L. The range of TSH circadian variability reached the level of 73%. According to the current TSH reference interval, hypothyroidism was not diagnosed in about 50% of the cases in the afternoon. The morning median TSH value in the patients taking l-thyroxine was 3.27 mU/L; it decreased to the value of 2.18 mU/L in the afternoon. The range of TSH circadian variability reached the level of 64.7%. Further analysis demonstrated inadequate compensation of hypothyroidism, which was defined in 45.5% of the morning samples and in 9% of the afternoon samples (p < 0.05). CONCLUSION: The time of blood sampling has an important role in the interpretation of TSH levels. Moreover, the high TSH circadian variability should be considered in discussions about the narrowing of its reference range.

A Novel GNAS Mutation in a Patient with Ia Pseudohypoparathyroidism (iPPSD2) Phenotype.

Pseudohypoparathyroidism (PHP) is a heterogeneous orphan disease characterized by multihormonal resistance and several phenotypic features. In some cases, PHP is caused by a mutation in the GNAS that encodes the alpha subunit of the G protein, one of the key transmitters of intracellular signals. A correlation between the genotype and phenotype of patients with GNAS mutations has not yet been described. This often makes diagnosis, drug prescription, and timely diagnosis difficult. Information about GNAS functioning and the impact of specific mutations on the clinical course of the disease is limited. Establishing of the pathogenicity by newly identified GNAS mutations will expand the understanding of this gene functioning in the cAMP signaling pathway and may become the basis for personalized treatment. This paper provides a clinical description of a patient with the Ia PHP phenotype caused by a previously unknown mutation in GNAS (NC_000020.11(NM_000516.7)): c.719-29_719-13delinsACCAAAGAGAGCAAAGCCAAG in the heterozygous state. Verification of the pathogenicity of the detected mutation is also described.

Denosumab for osteoporosis in patients with primary hyperparathyroidism and mild-to-moderate renal insufficiency.

PURPOSE: We aimed to assess the efficacy and safety of denosumab in postmenopausal women with primary hyperparathyroidism (PHPT)-related osteoporosis and chronic kidney disease (CKD). METHODS: Women over 50 years of age with PHPT or postmenopausal osteoporosis (PMO) were retrospectively recruited into this longitudinal study. These PHPT and PMO groups were further categorized into subgroups based on the presence of CKD (Glomerular filtration rate (GFR) < 60 mL/min/1.73 m2). All patients were given denosumab over 24 months due to verified osteoporosis. The primary outcomes were changes in bone mineral density (BMD) and serum calcium levels. RESULTS: 145 postmenopausal women median age 69 [63;77] were recruited and assigned to one of the subgroups: PHPT patients with CKD (n = 22), PHPT patients without CKD (n = 38), PMO patients with CKD (n = 17) and PMO patients without CKD (n = 68). Denosumab treatment significantly increased BMD in patients with PHPT-related osteoporosis and CKD: median T-score L1-L4 from -2.0 to -1.35 (p < 0.001), femur neck from -2.4 to -2.1 (p = 0.012), radius 33% from -3.2 to -3 (p < 0.05)) at 24 months. Changes in BMD were similar in all four studied groups compared to baseline. A marked decline in calcium was noted in the primary study group of PHPT with CKD (median ΔCa = -0.24 mmol/L p < 0.001), compared to PHPT without CKD (median ΔCa = -0.08 mmol/L p < 0.001) and PMO with or without CKD. Denosumab treatment was well-tolerated with no serious adverse events. CONCLUSION: Denosumab treatment was similarly effective at increasing BMD in patients with PHPT and PMO with and without renal insufficiency. The calcium lowering effects of denosumab were most significant in patients with PHPT and CKD. The safety of denosumab did not differ among participants with and without CKD.

The Russian registry of primary hyperparathyroidism, latest update.

Introduction: 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. Materials and methods: 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/). Results: 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. Conclusion: 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.

Circulating Plasma MicroRNA in Patients With Active Acromegaly.

CONTEXT: Excessive production of growth hormone causes marked multiorgan changes in patients with acromegaly, which may involve epigenetic mechanisms. OBJECTIVE: To evaluate differences in circulating microRNAs (miRNAs) associated with chronic growth hormone overproduction in adults. DESIGN AND SETTING: A cross-sectional case-control study was conducted at a tertiary medical center. PARTICIPANTS: We enrolled 12 consecutive patients with acromegaly along with 12 age- and sex-matched controls in the discovery phase of the study and then extended this cohort to 47 patients with acromegaly and 28 healthy controls for the validation study. MAIN OUTCOME MEASURES: Plasma miRNAs were quantified by next-generation sequencing (NGS) in the discovery phase. Levels of selected miRNAs were validated on extended cohorts using reverse transcription quantitative polymerase chain reaction (RT-qPCR), compared between groups, and correlated with clinical parameters. RESULTS: Based on NGS data, we selected 3 plasma miRNAs downregulated in patients with acromegaly compared to healthy controls: miR-4446-3p -1.317 (P = 0.001), miR-215-5p -3.040 (P = 0.005), and miR-342-5p -1.875 (P = 0.013) without multiplicity correction for all 3 miRNAs. These results were confirmed by RT-qPCR in the validation phase for 2 miRNAs out of 3: miR-4446-3p (P < 0.001, Padjusted < 0.001), area under the receiver-operator curve (AUC) 0.862 (95% CI 0.723-0.936; P < 0.001) and miR-215-5p (P < 0.001, Padjusted < 0.001), AUC 0.829 (95% CI 0.698-0.907; P < 0.001) to differentiate patients with acromegaly from healthy controls. CONCLUSIONS: In a 2-phase experiment using 2 different techniques we found and validated the downregulation of plasma miR-4446-3p and miR-215-5p in patients with acromegaly compared to healthy subjects, which makes them promising biomarkers for further research.

Association of Alleles of Human Leukocyte Antigen Class II Genes and Severity of COVID-19 in Patients of the 'Red Zone' of the Endocrinology Research Center, Moscow, Russia.

The aim of this study was to assess the correlations of clinical features of patients with moderate and severe courses of COVID-19, comorbidity (endocrine, autoimmune, cardiovascular, oncological, and pulmonary diseases), and alleles of the HLA class II system genes. One hundred COVID-19 patients hospitalized in the Endocrinology Research Centre, Moscow, Russia, were analyzed for age, gender, smoking, comorbidity, and invasive mechanical ventilation. Computer tomography was used to assess the severity of the disease. HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles were identified in samples from 100 patients and samples from 327 randomly selected individuals collected in the prepandemic period (control group). There was no association of gender, age, weight, body mass index, smoking, and comorbidity with the severity of COVID-19. Allele DQB1*06:02-8 was more common in patients (p < 0.00005), and DQB1*06:01 and DQB1*05:03 were more common in the control group (p < 0.00005, and p = 0.0011, respectively). DQB1*06:02-8 can probably be considered as predisposing to moderate and severe COVID-19, and DQB1*06:01 can be considered as protective. No association of these alleles with comorbidity was found. Our results suggest that carriers of predisposing alleles, with cardiovascular and non-autoimmune endocrine diseases, should take more stringent preventive measures, and if infected, a more aggressive COVID-19 treatment strategy should be used.

The Russian Registry of Chronic Hypoparathyroidism.

INTRODUCTION: Chronic hypoparathyroidism is a relatively rare disease associated with multicomponent medical therapy and various complications. The analysis of large databases of patients with chronic hypoparathyroidism is a necessary tool to enhance quality of medical care, as well as to determine the optimal clinical and therapeutic approaches, and prognostic markers of the disease. THE AIM: of this study is to estimate the clinical and biochemical profile, long-term complications, medical therapy and disease control of the patients with chronic postsurgical and non-surgical hypoparathyroidism. MATERIALS AND METHODS: the cross-sectional, observational, continuous study was based on the Russian Registry of patients with hypoparathyroidism. 544 patients from 63 regions of the Russian Federation were included in this study. RESULTS: The majority of cases had postsurgical etiology (88.4%). Postsurgical hypoparathyroidism prevailed in females (р<0.001). About a half of patients had blood calcium and phosphorus targets, 56 and 52% respectively. Nephrolithiasis was confirmed in 32.5%, nephrocalcinosis - in 12.3% of cases. The risk of nephrocalcinosis/nephrolithiasis increased by 1.85 times with disease duration more than 4.5 years. The cataract was found in 9.4%. The cut-off point for the development of cataracts was 9.5 years, with a 6.96-fold increased risk. The longer duration of hypoparathyroidism of any etiology was associated with more frequent cataract (p=0.0018).We found brain calcification in 4%, arrhythmias in 7.2% and neuropsychiatric symptoms in 5.15% of cases. Generally, the BMD in the studied group corresponded to age values, and there was no evidence for the phenomenon of high bone density. TBS was consistent with normal bone microarchitectonics. In our study, the majority of patients (83.5%) was treated with standard therapy of calcium and vitamin D supplements. 5 patients with severe disease course were treated with rhPTH (1-34). CONCLUSIONS: Analysis of the presented database indicates insufficient diagnosis of the complications associated with chronic hypoparathyroidism. Overall, hypoparathyroidism is associated with higher risks of renal stone formation, decreased GFR, cataract especially in patients with longer duration of disease.

Mathematical model for preoperative differential diagnosis for the parathyroid neoplasms.

Background and objective: Preoperative diagnosis of parathyroid carcinoma (PC) is critical for the determination of the scope of surgical intervention. Nowadays, specific diagnostic markers for differentiation of PC and benign tumors are unknown, and less than half of patients with PC undergo necessary en bloc surgery. The aim of this study was to develop the instrument for preoperative diagnosis of PC. Methods: A multi-center retrospective study included 242 patients with primary hyperparathyroidism: 50 patients with PC, 30 with аtypical adenoma (AA), and 162 with adenoma of the parathyroid glands. Results: Patients with PC and AA had higher levels of PTH, ionized and albumin-corrected calcium, ALP, volume and the largest diameter of neoplasm, and the higher frequency of GFR decrease less than 60 ml/min/1.73 m2 compared to patients with adenoma. The frequency of low-energy fractures was higher in the carcinoma group versus the adenoma group (32% vs 8%). Heterogeneous structure and indefinite contour of glands detected by US were more typical for PC than for AA and adenomas. The mathematical model was developed using CatBoost gradient boosting algorithm for the noninvasive preoperative differential diagnosis of PC, AA, and adenoma. Conclusions: Model can predict adenoma with PPV 100% and PC with PPV 81-92%. Using model clinicians could plan extended en bloc resection for PC and selective parathyroidectomy for adenoma. If AA is predicted, he has to make a decision on the choice of the necessary volume of PTE based on his experience, because AA are the zone of uncertainty.

Atypical progeroid syndrome (p.E262K LMNA mutation): a rare cause of short stature and osteoporosis.

SUMMARY: Lamin A/C (LMNA) gene mutations cause a heterogeneous group of progeroid disorders, including Hutchinson-Gilford progeria syndrome, mandibuloacral dysplasia, atypical progeroid syndrome (APS) and generalized lipodystrophy-associated progeroid syndrome (GLPS). All of those syndromes are associated with some progeroid features, lipodystrophy and metabolic complications but vary differently depending on a particular mutation and even patients carrying the same gene variant are known to have clinical heterogeneity. We report a new 30-year-old female patient from Russia with an APS and generalized lipodystrophy (GL) due to the heterozygous de novo LMNA p.E262K mutation and compare her clinical and metabolic features to those of other described patients with APS. Despite many health issues, short stature, skeletal problems, GL and late diagnosis of APS, our patient seems to be relatively metabolically healthy for her age when compared to previously described patients with APS. LEARNING POINTS: Atypical progeroid syndromes (APS) are rare and heterogenic with different age of onset and degree of metabolic disorders, which makes this diagnosis very challenging for clinicians and may be missed until the adulthood. The clinical picture of the APS depends on a particular mutation in the LMNA gene, but may vary even between the patients with the same mutation. The APS due to a heterozygous LMNA p.E262K mutation, which we report in this patient, seems to have association with the generalized lipodystrophy, short stature and osteoporosis, but otherwise, it seems to cause relatively mild metabolic complications by the age of 30. The patients with APS and lipodystrophy syndromes require a personalized and multidisciplinary approach, and so they should be referred to highly specialized reference-centres for diagnostics and treatment as early as possible. Because of the high heterogeneity of such a rare disease as APS, every patient's description is noteworthy for a better understanding of this challenging syndrome, including the analysis of genotype-phenotype correlations.

Novel Gene Mutations Regulating Immune Responses in Autoimmune Polyglandular Syndrome With an Atypical Course.

CONTEXT: Autoimmune polyglandular syndrome (APS) is a cluster of endocrine disorders arising from immune dysregulation, often combined with damage to nonendocrine organs. There are 2 types of APS: type 1 and type 2 (APS-1 and APS-2, respectively). In clinical practice, an atypical course of APS is often observed. OBJECTIVE: This work aims to find a novel genetic predictor of APS. METHODS: We performed exome sequencing in 2 patients with an atypical clinical APS picture and members of their families. Patient A presented with a manifestation of APS-2 in early childhood and patient B with a late manifestation of the main components of APS-1. RESULTS: In patient B, we identified inherited compound mutations as a novel combination of the c.769C > T and c.821delG alleles of AIRE and genetic variation in the CIITA gene. No homozygous or compound mutations in AIRE were found in patient A, but we did reveal mutations in genes encoding regulatory proteins of innate and acquired immunity in this patient. CONCLUSION: Our data revealed novel combination of mutations in the AIRE gene in atypical APS and imply that mutations in immune-related genes may modify the clinical manifestation of APS in AIRE-mutation carriers and contribute to the development of autoimmune pathology in non-AIRE carriers with atypical APS.

Serum circulating miRNA-342-3p as a potential diagnostic biomarker in parathyroid carcinomas: A pilot study.

OBJECTIVE: To compare the serum miRNA expression profiles between patients with benign and malignant parathyroid tumours. BACKGROUND: Despite recent advances in molecular biology, a histological tissue biopsy is still the method of choice used to diagnose most cancers. The preoperative cytology is not an applicable method for diagnosis of parathyroid cancer (PC); therefore, huge interest exists in terms of finding alternative methodologies to seek specific cancer biomarkers. DESIGN: A retrospective cross-sectional study. PATIENTS AND METHODS: Serum samples of patients with PC (n = 13) and parathyroid adenoma (PA) (n = 11), age (p = .999) and sex (p = .999) were matched and examined via the simultaneous comparative expression analysis of 754 microRNAs (miRNAs). The «TaqMan OpenArray Human MicroRNA Panel¼ (Applied Biosystems) was used to conduct real-time PCRs using the «QuantStudio 12К Flex¼ station (Life Technologies). RESULTS: According to the results of a pilot study, significant changes in expression levels between the PC group and the PA group (control) (p < .05) were observed for 17 miRNAs. Among them, the downregulation of miRNA-342-3p met the Benjamini-Hochberg adjustment criteria for multiple comparisons (p = .02). CONCLUSIONS: Serum miRNA-342-3p could be a promising biomarker for PC to improve diagnosis and prognosis.

Clinical course and outcome of patients with ACTH-dependent Cushing's syndrome infected with novel coronavirus disease-19 (COVID-19): case presentations.

OBJECTIVE: To analyze the clinical presentations of patients with endogenous Cushing's syndrome (CS) affected by Coronavirus disease-19 (COVID-19). MATERIALS AND METHODS: Patients who were referred to our clinic with active CS from 31st March to 15th May 2020 were screened for COVID-19 using real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Late-night serum cortisol (64-327 nmol/L), late-night salivary cortisol (LNSC) (0.5-9.4 nmol/L), or 24-h urinary free cortisol (24 hUFC) (100-379 nmol/24 h) were measured by electrochemiluminescence immunoassay. RESULTS: Among 22 patients with active CS we found three cases affected by COVID-19. Nonspecific inflammation markers were within the reference range or slightly elevated in these patients. A 71-year-old woman with newly diagnosed CS (late-night serum cortisol >1750 nmol/L, LNSC 908.6 nmol/L) developed dyspnea as an only symptom and died from bilateral polysegmantal hemorrhagic pneumonia 7 days later. A 38-year-old woman with a 5-year medical history of active Cushing's disease (CD) (late-night serum cortisol 581.3 nmol/L, 24 hUFC 959.7 nmol/24-h) suffered from dyspnea, cough, fever (39.3 °C) and chest pain. Oxygen therapy, antibiotics and symptomatic treatments lead to full recovery 24 days later. A 66-year-old woman with a 4-year medical history of mild CD (late-night serum cortisol 603.4 nmol/L, LNSC 10.03 nmol/L) tested positive for COVID-19 in routine screening and remained asymptomatic. CONCLUSIONS: The outcome of COVID-19 in patients with CS depends on the severity of hypercortisolism. Thus, severe hypercortisolism is a warning sign that CS affected by COVID-19 could require emergency care despite a lack of clinical presentations and low inflammation biomarkers.

Effect on carbohydrate metabolism and analysis of acceptability (menstrual cycle control) of extended regimens of the vaginally inserted hormone-releasing system 'NuvaRing' as compared with the standard 21/7 regime in reproductive-age women with type 1 diabetes mellitus.

AIM: To evaluate the effect of the vaginally inserted hormone-releasing system 'NuvaRing' on carbohydrate metabolism and acceptability (menstrual cycle control) of extended regimens of using as compared with the standard regimen (21/7) in women with type 1 diabetes mellitus (DM) in reproductive period during 24 months. METHODS: The open randomised study included a total of 109 women with type 1 DM, using 'NuvaRing' in different regimens (21/7, 42/7, 84/7 and 357/7). Average daily insulin requirements, the levels of glycosylated haemoglobin were determined at baseline, after 6, 12, 18 and 24 months of contraception. The control group was composed of 22 age-matched women with type 1 DM using no methods of contraception. RESULTS: Using the contraceptive system 'NuvaRing' in type 1 DM women in the reproductive period has proved to exert no clinically significant effect on carbohydrate metabolism in prolonged regimens, as well as in standard regimen. The overall number of bleeding days and spotting days was comparable in different groups. Longer regimens with fewer breaks were associated with fewer days of bleeding but a larger number of spotting days as compared with the shorter regimens, with a tendency towards a gradual decrease in spotting days during a year. CONCLUSION: The releasing system 'NuvaRing' proved to be a reliable and safe means of contraception for late reproductive age women with type 1 DM.