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1.
Biomedicines ; 12(4)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38672138

RESUMO

Osteoarthritis is a chronic progressive joint disease that clinically debuts at the stage of pronounced morphologic changes, which makes treatment difficult. In this regard, an important task is the study of genetic markers of the disease, which have not been definitively established, due to the clinical and ethnic heterogeneity of the studied populations. To find the genetic markers for the development of knee osteoarthritis (OA) in women from the Volga-Ural region of Russia, we conducted research in two stages using different genotyping methods, such as the restriction fragment length polymorphism (RFLP) measurement, TaqMan technology and competitive allele-specific PCR-KASPTM. In the first stage, we studied polymorphic variants of candidate genes (ACAN, ADAMTS5, CHST11, SOX9, COL1A1) for OA development. The association of the *27 allele of the VNTR locus of the ACAN gene was identified (OR = 1.6). In the second stage, we replicated the GWAS results (ASTN2, ALDH1A2, DVWA, CHST11, GNL3, NCOA3, FILIP/SENP1, MCF2L, GLT8D, DOT1L) for knee OA studies. The association of the *T allele of the rs7639618 locus of the DVWA gene was detected (OR = 1.54). Thus, the VNTR locus of ACAN and the rs7639618 locus of DVWA are risk factors for knee OA in women from the Volga-Ural region of Russia.

2.
Anal Methods ; 16(9): 1415, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38333946

RESUMO

Correction for 'Body composition analysis via spatially resolved NIR spectroscopy with multifrequency bioimpedance precision' by Evgeny Shirshin et al., Anal. Methods, 2024, 16, 175-178, https://doi.org/10.1039/D3AY01901B.

3.
Biomedicines ; 12(2)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38398001

RESUMO

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.

4.
Anal Methods ; 16(2): 175-178, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38099917

RESUMO

Near-infrared spectroscopy (NIRS) is often criticized due to its insufficient accuracy in determining body composition compared to the gold standard methods. In this work, we show that the use of multiple source-detector distances, as well as the simultaneous use of physiological and optical features, can significantly improve the accuracy of determination of fat and lean mass percentage in the human body using NIR spectroscopy. The study performed on the n = 292 cohort revealed the mean absolute errors of 3.5% for fat content and 3.3% for soft lean mass percentage prediction (r = 0.93) using the multifrequency bioimpedance analysis (BIA) as a reference. Hence, NIRS can serve as an independent reliable method for body composition analysis with precision close to that of advanced multifrequency BIA.


Assuntos
Composição Corporal , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Impedância Elétrica , Composição Corporal/fisiologia
5.
Int J Mol Sci ; 24(24)2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38139149

RESUMO

Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by the destruction of insulin-producing ß-cells in the pancreas by cytotoxic T-cells. To date, there are no drugs that can prevent the development of T1D. Insulin replacement therapy is the standard care for patients with T1D. This treatment is life-saving, but is expensive, can lead to acute and long-term complications, and results in reduced overall life expectancy. This has stimulated the research and development of alternative treatments for T1D. In this review, we consider potential therapies for T1D using cellular regenerative medicine approaches with a focus on CRISPR/Cas-engineered cellular products. However, CRISPR/Cas as a genome editing tool has several drawbacks that should be considered for safe and efficient cell engineering. In addition, cellular engineering approaches themselves pose a hidden threat. The purpose of this review is to critically discuss novel strategies for the treatment of T1D using genome editing technology. A well-designed approach to ß-cell derivation using CRISPR/Cas-based genome editing technology will significantly reduce the risk of incorrectly engineered cell products that could behave as a "Trojan horse".


Assuntos
Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/terapia , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Insulina/genética , Terapia Baseada em Transplante de Células e Tecidos
6.
Biomedicines ; 11(11)2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-38001982

RESUMO

Peak bone mass is the amount of bone tissue that is formed when a stable skeletal state is achieved at a young age. To date, there are no established peak bone mass standards nor clear data on the age at which peak bone mass occurs. At the same time, the level of peak bone mass at a young age is an important predictor of the onset of primary osteoporosis. The purpose of this review is to analyze the results of studies of levels of peak bone mass in general, the age of its onset, as well as factors influencing its formation. Factors such as hormonal levels, body composition, physical activity, nutrition, heredity, smoking, lifestyle, prenatal predictors, intestinal microbiota, and vitamin and micronutrient status were considered, and a comprehensive scheme of the influence of these factors on the level of peak bone mass was created. Determining the standards and timing of the formation of peak bone mass, and the factors affecting it, will help in the development of measures to prevent its shortage and the consequent prevention of osteoporosis and concomitant diseases.

8.
Genes (Basel) ; 14(10)2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37895301

RESUMO

INTRODUCTION: Non-diabetic hypoglycemia (NDH) is a collective term including the multiple causes of hypoglycemic syndrome not due to diabetes mellitus. NDH may result from insulinoma, IGF-2-omas, hypocorticism, Hirata's disease, genital disorders of glucose metabolism, etc. One of the most common causes of NDH faced by an endocrinologist is insulinoma, which in turn can be part of the hereditary syndrome of multiple endocrine neoplasia type 1 (MEN1). Congenital disorders of glucose metabolism in adult patients, on the contrary, are diagnosed extremely rarely, since they usually manifest in childhood. This article presents a unique clinical case of a patient with NDH and genetically verified MEN1 in combination with congenital hyperinsulinism due to an ABCC8 gene mutation. CASE REPORT: A 43-year-old patient with hypoglycemic symptoms from childhood is presented, in whom multiple pancreatic tumors and fluctuations in glycemia from 38.7 mg/dL to 329.7 mg/dL (2.15 to 18.3 mmol/L) were detected in adulthood, but a mild course of hypoglycemic syndrome was noted. Numerous examinations that were performed to establish an accurate diagnosis are described, signs that served as a reason for expanding the complex of studies are indicated, possible pathogenetic mechanisms of the mild course of hypoglycemic syndrome and hyperglycemic conditions are discussed. CONCLUSION: This case report is original and highlights that we must always remain intolerant of the inexplicable. Conducting an extended gene study can help perform a correct diagnosis in complex cases.


Assuntos
Hiperinsulinismo Congênito , Insulinoma , Neoplasia Endócrina Múltipla Tipo 1 , Adulto , Humanos , Neoplasia Endócrina Múltipla Tipo 1/genética , Insulinoma/genética , Insulinoma/patologia , Mutação em Linhagem Germinativa , Hipoglicemiantes , Glucose , Receptores de Sulfonilureias/genética
9.
Front Endocrinol (Lausanne) ; 14: 1266728, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37842310

RESUMO

Introduction: Cardiovascular diseases (CVD) and metabolic disorders (MD) have retained leading positions in the structure of morbidity and mortality for many years. Primary hyperparathyroidism (PHPT) is also associated with a greater incidence of CVD and MD. The aim of the present study was to describe the prevalence and structure of CVD and MD in hospitalized patients with PHPT and to search for possible associations between these pathologies. Methods: 838 patients with a verified PHPT were included in the study. The studied cohort was divided into 2 groups according to their age at the time of admission: patients aged 18 to 49 years (group A, n = 150); patients aged 50 years and older (group B, n = 688). Results: There were no significant differences between two groups in parameters of calcium-phosphorus metabolism. Obesity was diagnosed in 24.2% of patients in group A and in 35.9% in group B. Type 2 diabetes mellitus was more common in older patients (14.4% in group B vs. 2.6% in group A). Arterial hypertension, ischemic heart disease, chronic heart failure and brachiocephalic arteries atherosclerosis were more frequent in older patients, occurring in 79.1%, 10.8%, 8.4%, and 84% of cases respectively. The cutoff points that increased the risk of CVD detection turned out to be age above 56 years, eGFR below 92 ml/min/1.73m2, BMI above 28.3 kg/m2. Discussion: The present study demonstrated a high incidence of some CVD, as well as disorders of lipid, carbohydrate and purine metabolism in patients with PHPT.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Hiperparatireoidismo Primário , Hipertensão , Humanos , Pessoa de Meia-Idade , Idoso , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Fatores de Risco , Hipertensão/complicações , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/complicações
10.
Front Endocrinol (Lausanne) ; 14: 1218686, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37560295

RESUMO

Introduction: Adrenocortical cancer (ACC) is a rare malignant tumor that originates in the adrenal cortex. Despite extensive molecular-genetic, pathomorphological, and clinical research, assessing the malignant potential of adrenal neoplasms in clinical practice remains a daunting task in histological diagnosis. Although the Weiss score is the most prevalent method for diagnosing ACC, its limitations necessitate additional algorithms for specific histological variants. Unequal diagnostic value, subjectivity in evaluation, and interpretation challenges contribute to a gray zone where the reliable assessment of a tumor's malignant potential is unattainable. In this study, we introduce a universal mathematical model for the differential diagnosis of all morphological types of ACC in adults. Methods: This model was developed by analyzing a retrospective sample of data from 143 patients who underwent histological and immunohistochemical examinations of surgically removed adrenal neoplasms. Statistical analysis was carried out on Python 3.1 in the Google Colab environment. The cutting point was chosen according to Youden's index. Scikit-learn 1.0.2 was used for building the multidimensional model for Python. Logistical regression analysis was executed with L1-regularization, which is an effective method for extracting the most significant features of the model. Results: The new system we have developed is a diagnostically meaningful set of indicators that takes into account a smaller number of criteria from the currently used Weiss scale. To validate the obtained model, we divided the initial sample set into training and test sets in a 9:1 ratio, respectively. The diagnostic algorithm is highly accurate [overall accuracy 100% (95% CI: 96%-100%)]. Discussion: Our method involves determining eight diagnostically significant indicators that enable the calculation of ACC development probability using specified formulas. This approach may potentially enhance diagnostic precision and facilitate improved clinical outcomes in ACC management.


Assuntos
Neoplasias do Córtex Suprarrenal , Adenoma Adrenocortical , Carcinoma Adrenocortical , Adulto , Humanos , Adenoma Adrenocortical/patologia , Carcinoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/patologia , Estudos Retrospectivos , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/cirurgia , Neoplasias do Córtex Suprarrenal/patologia , Análise de Regressão
11.
Front Endocrinol (Lausanne) ; 14: 1203437, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37465121

RESUMO

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.


Assuntos
Adenoma , Hiperparatireoidismo Primário , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Cálcio , Estudos Retrospectivos , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/epidemiologia , Hiperparatireoidismo Primário/genética , Estudos Transversais , Sistema de Registros , Cálcio da Dieta , Adenoma/complicações , Fósforo
12.
Artigo em Inglês | MEDLINE | ID: mdl-37183888

RESUMO

Summary: A 59-year-old male presented with an accidental thyroid mass in 2022. Ultrasound and CT scan showed a nodule 5.2 × 4.9 × 2.8 cm (EU-TIRADS 4) in the right lobe of the thyroid gland. Taking into account the results of the fine needle aspiration biopsy (Bethesda V), intrathyroid localization, and absence of clinical symptoms, a malignant tumor of the thyroid gland was suspected. The patient underwent total thyroidectomy using fluorescence angiography with indocyanine green, and two pairs of intact parathyroid glands were visualized in typical localization. Unexpected histological and immunohistochemistry examinations revealed parathyroid carcinoma. Due to the asymptomatic course of the disease and atypical localization of parathyroid tumor, primary hyperparathyroidism was not suspected before the surgery. The diagnosis of asymptomatic intrathyroid parathyroid cancer is a serious diagnostic challenge for a wide range of specialists. Learning points: Parathyroid cancer is a rare disease that may be asymptomatic. Intrathyroidal localization of parathyroid carcinoma is casuistic and challenging for diagnosis, and the treatment strategy is not well defined. Preoperative parathyroid hormone and serum calcium testing are recommended for patients with solid thyroid nodules (Bethesda IV-V).

13.
Int J Mol Sci ; 24(9)2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-37175816

RESUMO

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.


Assuntos
Espectrometria de Mobilidade Iônica , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Ergocalciferóis , Vitaminas , Vitamina D
14.
BMC Endocr Disord ; 23(1): 57, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36890506

RESUMO

BACKGROUND: Components of metabolic syndrome can be observed in patients with primary hyperparathyroidism (PHPT). The link between these disorders remains unclear due to the lack of relevant experimental models and the heterogeneity of examined groups. The effect of surgery on metabolic abnormalities is also controversial. We conducted a comprehensive assessment of metabolic parameters in young patients with PHPT. METHODS: One-center prospective comparative study was carried out. The participants underwent a complex biochemical and hormonal examination, a hyperinsulinemic euglycemic and hyperglycemic clamps, a bioelectrical impedance analysis of the body composition before and 13 months after parathyroidectomy compared to sex-, age- and body mass index matched healthy volunteers. RESULTS: 45.8% of patients (n = 24) had excessive visceral fat. Insulin resistance was detected in 54.2% of cases. PHPT patients had higher serum triglycerides, lower M-value and higher C-peptide and insulin levels in both phases of insulin secretion compared to the control group (p < 0.05 for all parameters). There were tendencies to decreased fasting glucose (p = 0.031), uric acid (p = 0.044) and insulin levels of the second secretion phase (p = 0.039) after surgery, but no statistically significant changes of lipid profile and M-value as well as body composition were revealed. We obtained negative correlations between percent body fat and osteocalcin and magnesium levels in patients before surgery. CONCLUSION: PHPT is associated with insulin resistance that is the main risk factor of serious metabolic disorders. Surgery may potentially improve carbohydrate and purine metabolism.


Assuntos
Hiperparatireoidismo Primário , Resistência à Insulina , Humanos , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/cirurgia , Insulina , Estudos Prospectivos , Secreção de Insulina
15.
J Pers Med ; 13(3)2023 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-36983729

RESUMO

Parathyroid cancer is a rare, clinically aggressive malignancy with a prevalence of approximately 0.005% relative to all carcinoma cases and 1-5% among patients with primary hyperparathyroidism. Prognosis largely depends on the extent of the primary surgery. Non-radical surgical treatment increases the risk of local and distant metastases of the parathyroid cancer associated with limited treatment options. The combination of thyroid and parathyroid disorders has been described rather well for the general population; however, cases of parathyroid and thyroid carcinoma in the same patient are extremely rare (1 case per 3000 patients with parathyroid disorders). We present a rare clinical case of combination of parathyroid and thyroid cancers with metastases of both tumors to the neck lymph nodes in a woman with a mutation in the MEN1 gene (NM_130799.2): c.658T > C p.Trp220Arg (W220R), who has been exposed to radiation for 20 years before diagnosis of thyroid cancer and received renal replacement therapy with long-term hemodialysis before the diagnosis of parathyroid cancer. The patient underwent several surgeries because of metastases of the parathyroid cancer in the neck lymph nodes. Surgeons used intraoperative navigation methods (single-channel gamma detection probe, Gamma Probe 2, and fluorescence angiography with indocyanine green (ICG)) to clarify the volume of surgery. Currently, the patient is still in laboratory remission, despite the structural recurrence of tumors.

16.
Genes (Basel) ; 14(2)2023 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-36833251

RESUMO

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.


Assuntos
Subunidades alfa Gs de Proteínas de Ligação ao GTP , Pseudo-Hipoparatireoidismo , Humanos , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Cromograninas/genética , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/genética , Mutação , Fenótipo
17.
Front Endocrinol (Lausanne) ; 14: 1292993, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38250739

RESUMO

Sagliker syndrome (SS) is an extremely rare disorder that manifests in patients with advanced chronic kidney disease (CKD) undergoing programmed hemodialysis as a renal replacement therapy. Treatment of secondary hyperparathyroidism (SHPT) in these patients is still challenging. The main clinical manifestations of SS include craniofacial and fingertip deformities, dental anomalies, gingival hyperplasia, short stature, hearing loss, neurological and psychiatric impairment. The etiology and pathogenesis of SS in patients with SHPT require further clarification. However, mutations in the GNAS1, FGF23, and FGFR3 genes were described in some patients, suggesting a possible role of genetic predisposition to the syndrome. The preferred therapeutic approach for SS is surgery, but the volume of the operation is debated. The main surgical strategies include total, subtotal parathyroidectomy, or total parathyroidectomy with autotransplantation of the parathyroid gland (PG). Unfortunately, parathyroidectomy does not contribute to the regression of significant skeletal deformities. We present a unique clinical case of a patient with classical features of SS, recurrent tertiary hyperparathyroidism (THPT) after total parathyroidectomy due to intrathyroidal parathyroid carcinoma (PC).


Assuntos
Carcinoma , Hiperparatireoidismo , Neoplasias das Paratireoides , Humanos , Glândulas Paratireoides , Hiperparatireoidismo/complicações , Hiperparatireoidismo/cirurgia , Paratireoidectomia
18.
J Clin Med ; 13(1)2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38202014

RESUMO

BACKGROUND: findings from the previously conducted studies indicate altered regulatory mechanisms of calcium and vitamin D metabolism in obese patients and a role for bariatric surgery in regulating vitamin D metabolism; however, the available data is controversial and does not provide an adequate understanding of the subject. METHODS: we evaluated serum parameters of vitamin D and mineral metabolism (vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3, and 24,25(OH)2D3), vitamin D-binding protein (DBP), free 25(OH)D, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), total calcium, albumin, phosphorus, creatinine, magnesium) in 30 patients referred for bariatric surgery in comparison with 30 healthy volunteers of similar age, sex and baseline 25(OH)D3. Patients were also followed up with repeated laboratory assessments 3 months and 6 months after surgery. During the first 3 months, patients were prescribed high-dose cholecalciferol therapy (50,000 IU per week), with subsequent correction based on the results of the 3-month visit examination. RESULTS: Preoperatively, patients with morbid obesity were characterized by a high prevalence of vitamin D deficiency (median 25(OH)D3 level 11.9 (6.8; 22.2) ng/mL), significantly lower levels of active vitamin D metabolite 1,25(OH)2D3 (20 (10; 37) vs. 39 (33; 50) pg/mL, p < 0.001), lower serum albumin-adjusted calcium levels (2.24 (2.20; 2.32) vs. 2.31 (2.25; 2.35) mmol/L, p = 0.009) and magnesium levels (0.79 (0.72; 0.82) vs. 0.82 (0.78; 0.85) mmol/L, p = 0.043) with simultaneous similar PTH levels (p = 0.912), and higher DBP levels (328 (288; 401) vs. 248 (217; 284) mg/L, p < 0.001). The 25(OH)D3 levels remained suboptimal (24.5 (14.7; 29.5) ng/mL at the 3-month visit and 17.9 (12.4; 21.0) ng/mL at the 6-month visit, p = 0.052) despite recommended high-dose cholecalciferol supplementation. Patients also demonstrated an increase in 1,25(OH)2D3 levels (38 (31; 52) pg/mL at the 3-month visit and 49 (29; 59) pg/mL at the 6-month visit, p < 0.001) without a change in PTH or calcium levels during the follow-up. CONCLUSION: our results of a comprehensive laboratory evaluation of vitamin D status and mineral metabolism in patients undergoing bariatric surgery highlight the importance of improving current clinical guidelines, as well as careful monitoring and education of patients.

19.
Metabolites ; 12(12)2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36557317

RESUMO

Only a few studies evaluating the metabolism of vitamin D in patients with hypoparathyroidism (HypoPT) have been performed thus far, and, in particular, they mainly investigated the process of vitamin D activation (specifically, 1α-hydroxylation). This study, therefore, aimed to evaluate the extended spectrum of vitamin D metabolites in patients with HypoPT compared to healthy individuals. We examined 38 adult patients with chronic HypoPT in comparison to 38 healthy adults. The assessment included biochemical parameters (total calcium, albumin, phosphorus, creatinine, and magnesium), parathyroid hormone (PTH), and vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3, and 24,25(OH)2D3) in serum. Our data show that an adequate level of 25(OH)D3 (median 35.3 (29.6; 42.0) ng/mL) is achieved with standard doses of cholecalciferol (median 2000 (2000; 2500) IU per day) in HypoPT patients. They also presented with supraphysiological levels of 1,25(OH)2D3 (median 71 (47; 96) vs. 40 (34; 59) pg/mL, p < 0.001) and the increased production of inactive metabolite (median 24,25(OH)2D3 3.8 (3.0; 5.1) vs. 1.9 (1.3; 2.7) ng/mL, p < 0.001; median 25(OH)D3/24,25(OH)2D3 ratio 8.9 (7.6; 11.1) vs. 13.5 (11.1; 17.0), p < 0.001) as compared to the control group. This might be a consequence of the therapy received (treatment with activated vitamin D) and the pathophysiology of the disease (lack of PTH). The abnormality of vitamin D metabolism does not seem to interfere with the achievement of hypoparathyroidism compensation.

20.
Diseases ; 10(4)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36412593

RESUMO

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.

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