Primary hyperparathyroidism in young patients is associated with metabolic disorders: a prospective comparative study.

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.

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.

Impaired Vitamin D Metabolism in Hospitalized COVID-19 Patients.

There is increasing data regarding the association between vitamin D and COVID-19. This study aimed to reveal the alterations of vitamin D metabolism in the setting of COVID-19. We examined 119 adult COVID-19 inpatients and 44 apparently healthy adult individuals with similar serum 25OH-D3 levels as a reference group. The assessment included serum biochemical parameters (total calcium, albumin, phosphorus, creatinine), parathyroid hormone (PTH), vitamin D-binding protein (DBP), vitamin D metabolites (25OH-D3, 25OH-D2, 1,25(OH)2D3, 3-epi-25OH-D3, 24,25(OH)2D3 and D3) and free 25OH-D. COVID-19 patients had in general very low vitamin D levels (median 25OH-D3 equals 10.8 ng/mL), accompanied by an increased production of the active vitamin D metabolite (1,25(OH)2D3), estimated as higher 1,25(OH)2D3 serum levels (61 [44; 81] vs. 40 [35; 50] pg/mL, p < 0.001) and lower 25OH-D3/1,25(OH)2D3 ratio (175 [112; 260] vs. 272 [200; 433], p < 0.001) which is presumably aimed at preventing hypocalcemia. Patients with COVID-19 also had elevated DBP (450 [386; 515] vs. 392 [311; 433] mg/L, p < 0.001) and low free 25OH-D levels (<LoB vs. 3.9 [3.2; 4.4] pg/mL, p < 0.001). Follow-up assessment of the COVID-19 inpatients showed recovery of the observed changes. Overall, hospitalized patients with an acute course of COVID-19 have not only very low levels of 25OH-D but also profound abnormalities in the metabolism of vitamin D regardless of the clinical course of the disease. These alterations might exacerbate existing vitamin D deficiency and its negative impact.

HbA1c Level in Severe COVID-19 Patients Is Not Only a Marker of Glycemic Status but Also of Acute Erythrocyte Damage

Introduction: COVID-19 can trigger either transient stress-induced state, or newly onset diabetes mellitus (DM). It is well known that HbA1c serves as an indicator of glycemic status 12 weeks before the acute disease. Aim: To examine glycemic status at admission and 6 weeks after hospital discharge in patients with confirmed COVID-19 but no previous DM-history. Methods: Of 155 patients hospitalized with COVID-19 and pneumonia 111 persons had no previous DM-history. The levels of HbA1с, fasting and admission plasma glucose (FPG and APG) were measured at admission and 6 weeks after the discharge. The severity of COVID-19 was confirmed by CT scan, SpO2, serum IL-6, CRP, D-dimer. Results: All 111 patients had normal FPG and APG values. According to HbA1c level all the patients were divided into two groups: A) HbA1c≤6.0% (n=64, median 5,8%) and B) HbA1c>6,0% (n=47, median 6,4%). Our particular interest was focused on the group B due to the discrepancy of high HbA1c level and normal FPG and APG. Group B patients were retested for glycemic status in 6±1 week after the discharge. Surprisingly the median HbA1c level dropped down from 6,4% to 5,7% in such a short period of time with no antidiabetic drugs. COVID-19 severity markers were significantly higher in the group B. Conclusions: We suggest two explanations for this faster than expected HbA1c decrease: 1) patients with HbA1c>6,0% will progress to DM later, and, therefore, a longer follow-up is needed;2) SARS-CoV-2 virus has extensively glycosylated spike(S)-protein that may bind to erythrocytes. High-pressure liquid chromatography (the standard method for HbA1c) probably fails to separate the glycated 1-β-chain of hemoglobin from glycated viral spikes. In this case, abnormally high HbA1c in COVID-19 patients with no DM-history may serve as a marker of severe viral erythrocyte damage rather than a marker for the glucose control. This hypothesis is confirmed by the prompt (in 6 weeks) normalization of HbA1c level following the virus elimination.

Vitamin D Metabolism Is Significantly Impaired in COVID-19 Inpatients

Objective: to assess the state of vitamin D metabolism in patients hospitalized with COVID-19 infection. Materials and methods: We examined 49 patients, which were hospitalized for inpatient treatment of COVID-19 infection from May to June 2020. Study group included 24 men (49%) and 25 women (51%), median age 58 years [48;70], BMI 26.4 kg/m2 [24.3;30.5]. All patients were diagnosed with pneumonia due to SARS-CoV-2 with median percent of lung involvement equal to 29% [14;37], 22 patients (45%) required oxygen support upon admission. Median SpO2 was equal to 95% (92;97), median NEWS score was equal to 3 [2;6]. Participants were tested for vitamin D metabolites (25(OH)D3, 1,25(OH)2D3, 3-epi-25(OH)D3, 24,25(OH)2D3 and D3) by UPLC-MS/MS, free 25(OH)D and vitamin D-binding protein by ELISA, as well as PTH by electrochemiluminescence immunoassay and routine biochemical parameters of blood serum (calcium, phosphorus, albumin) at the time of admission. Results: patients had in general very low 25()D3 levels - median 10.9 ng/mL [6.9;15.6], corresponding to a pronounced vitamin D deficiency in half of the patients. Levels of 24,25(OH)2D3 were also low – 0.5 ng/mL [0.2;0.9], and resulting vitamin D metabolite ratios (25(OH)D3/24,25(OH)2D3) were high-normal or elevated in most patients – 24.1 [19.0;39.2], indicating decreased activity of 24-hydroxylase. Levels of 1,25(OH)2D3, on the contrary, were high-normal or elevated - 57 pg/mL [46;79], which, in accordance with 25(OH)D3/1,25(OH)2D3 ratio (219 [134;266]) suggests an increase in 1α-hydroxylase activity. Median level of 3-epi-25(OH)D3 was 0.7 ng/mL [0.4;1.0] and D3 metabolite was detectable only in 6 patients. Median DBP level was 432 mg/L [382;498], median free 25(OH)D was 5.6 pg/mL [3.3;6.7], median calculated free 25(OH)D was 2.0 pg/mL [1.4;3.3]. Most patients had albumin-adjusted serum calcium level in the lower half of reference range (median 2.24 mmol/L [2.14;2.34]). Seven patients had secondary hyperparathyroidism and one patient had primary hyperparathyroidism, the rest of the patients had PTH levels within the normal range.25(OH)D3 levels showed significant negative correlation with percent of lung involvement (r = -0.36, p&lt;0.05) and positive correlation with SpO2 (r = 0.4, p&lt;0.05). 1,25(OH)2D3 levels correlated positively with 25(OH)D3 levels (r = 0.38, p&lt;0.05) and did not correlate significantly with PTH levels (p&gt;0.05). Conclusion: Our data suggests that hospitalized patients with COVID-19 infection have significant impairment of vitamin D metabolism, in particular, an increase in 1α-hydroxylase activity, which cannot be fully explained by pre-existing conditions such as vitamin D deficiency and secondary hyperparathyroidism. The observed profound vitamin D deficiency and association of vitamin D levels with markers of disease severity indicate the importance of vitamin D supplementation in these patients.

[The role of HLA genes: from autoimmune diseases to COVID-19].

Genes of HLA system (Human Leukocyte Antigen) play an essential role in the normal functioning of the immune system. There are three classes of genes: I, II, and III. The function of HLA molecules class I is to present antigens of peptides from the cytoplasm to T-lymphocytes on the cell surface, and class II - to present antigens of peptides from the extracellular space. In the classical view, the pathological activation of the immune system in patients with a genetic predisposition can result in the development of autoimmune diseases. However, the influence of this system on the development of non-autoimmune diseases, their severity and prognosis, has been recently considered. Besides, HLA molecules provide a presentation of various infectious agents. In this connection, the loci of the main histocompatibility complex can be considered candidates for determining the genetic predisposition to infectious diseases themselves and their course. This review hypothesizes that specific variants of HLA genes may cause the formation of a «cytokine storm¼ in patients with COVID-19. Identification of a group of patients with particular genetic variations that cause violation of immune tolerance and hyperresponse in the setting of viral infection will help to optimize the algorithm for disease prevention and treatment of such patients and, as a result, to reduce the severity of the epidemiological situation.

[COVID-19 pandemic and endocrinopathies].

Many endocrinopathies have chronic course; patients with endocrinopathies (above all diabetes mellitus and thyroid diseases) who receive outpatient care on a regular basis amount up to 80% of patients with chronic diseases. Endocrinologists most likely play the role of general practitioners for these patients; therefore, they should quickly and efficiently explain the patients with diabetes, thyroid, hypophysis and adrenal diseases how to behave in new setting of COVID19 pandemic (coronavirus infection). The most severe course of the infection can be observed in patients older than 65 years with chronic diseases, especially endocrinopathies. This review sums up the currently available data on the disease pathogenesis and progression. It also provides information about patient responsibility to prevent infection, special aspects of communication between the patient and the physician in the setting of self-isolation and quarantine, additional care needed in case of COVID19 in patients with most severe endocrinopathies.

COVID-19 AND KIDNEYS

COVID-19 poses a real threat to patients with comorbid conditions such as diabetes mellitus (DM), hypertension, cardiovascular, renal or hepatic disorders. Kidney damage is very likely in people with diabetes who have undergone a new infection, and the risk of developing acute renal injury is associated with mortality. Potential mechanisms of kidney involvement in the clinical picture of the disease may include cytokine damage, cross-organ damage, and systemic effects that determine the treatment strategy. These mechanisms are closely interrelated and are important for individuals on extracorporeal therapy and kidney transplants. Autopsy data provide evidence of SARS-CoV-2 virus invasion into kidney tissue with damage to tubular epithelium cells and podocytes, and red blood cell aggregation in severely COVID-19 patients. By including individuals with chronic kidney disease in planned COVID-19 research protocols, an evidence base for effective and safe treatments can be generated.

COURSE AND TREATMENT OF DIABETES MELLITUS IN THE CONTEXT OF COVID-19

In 2020, the world is facing a historically unparalleled public health challenge associated with the invasion of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This is also a challenge for the healthcare systems worldwide. Patients with diabetes mellitus (DM) are most vulnerable to COVID-19 because of the peculiarities of their immune response to a virus attack and due to their high susceptibility to viral activity because of hyperglycemia and other comorbid conditions and obesity that often accompany DM. The severity of the COVID-19 disease requires a mandatory review of the usual anti-hyperglycemic therapy. Maintaining optimal glycemic control and preventing the development of ketoacidosis remain extremely important;therefore, insulin becomes the priority drug for glycemic control in most cases. The search for new drugs to fight against the coronavirus infection continues with new randomised clinical drug trials being launched. Innovative anti-diabetic agents are also being tested as candidates for potentially effective anti-coronavirus agents.