Boyan Nonchev

Background: Thyroid hormones influence bone metabolism, and autoimmune thyroid diseases may further impact skeletal homeostasis. Wnt signaling inhibitors, including Dickkopf-1 (DKK-1) and sclerostin (SOST), as well as osteoprotegerin (OPG), play key roles in regulating bone formation and resorption. This study aimed to evaluate circulating DKK-1, SOST, and OPG in women with newly diagnosed overt thyroid dysfunction. Methods: This cross-sectional study included 62 women with newly diagnosed, untreated overt thyroid dysfunction (35 hypothyroid and 27 hyperthyroid) and 33 age- and BMI-matched healthy controls. Serum levels of DKK-1, sclerostin, and OPG were measured using ELISA. Thyroid function and autoantibodies were assessed using automated immunoassays. Correlation analysis was performed to evaluate associations between variables. Results: Serum DKK-1 levels were significantly elevated in both hypothyroid and hyperthyroid women compared with controls (p < 0.001). Sclerostin levels showed a non-significant trend toward higher values. OPG levels were significantly increased in hyperthyroid patients and moderately elevated in hypothyroid patients. Significant positive correlations were observed between OPG and FT3 (r = 0.42, p = 0.001) and FT4 (r = 0.43, p = 0.001). In hypothyroid patients, OPG correlated positively with TgAb (r = 0.46, p = 0.007). A strong positive correlation was found between DKK-1 and SOST (p < 0.001), while DKK-1 was negatively associated with age (p < 0.05). Conclusions: Overt thyroid dysfunction is associated with significant alterations in circulating Wnt signaling inhibitors and OPG. These findings suggest a potential role of Wnt signaling and immune–bone interactions in thyroid-related changes in bone metabolism.

Background: Inflammation plays a key role in the pathogenesis of type 2 diabetes (T2D) and the associated cardiovascular complications. High-sensitivity C-reactive protein (hsCRP) is a widely used marker of systemic inflammation as well as a predictor of cardiovascular risk. Objective: There is increasing evidence that glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, may have effects on hsCRP levels, independent of their effects on glycemic control and body weight loss. This purpose of our study is to explore the effect of semaglutide on hsCRP levels in patients with type 2 diabetes. Additionally, we aimed to determine whether the observed effect of semaglutide on hsCRP is fully mediated by changes in HbA1c and body weight, or whether there is a direct effect suggesting the presence of an independent anti-inflammatory mechanism. Methods: The study included 70 outpatients with diagnosed type 2 diabetes undergoing therapy with metformin and/or a sulfonylurea. Semaglutide was added to the existing therapeutic regimen. All participants were followed up after a 6-month a period. At the beginning and at the end of the study, the hsCRP values, some selected indicators of glycemic control, and the anthropometric measurements were recorded. Results: The mean hsCRP value at baseline was 4.90 ± 1.21 mg/L, while after six-month therapy, it dropped to 2.23 ± 2.21 mg/L. Conclusions: The results of the analysis have a good potential to contribute to a better understanding of the pleiotropic effects of GLP-1 RAs and support the hypothesis of a direct anti-inflammatory role of semaglutide, which could have clinical significance in the context of cardiometabolic risk management in patients with type 2 diabetes.

In metabolic syndrome, cardiomyocyte changes induced by metabolic and proinflammatory factors impair repolarization and exacerbate the heterogeneity of the transmural dispersion of repolarization, and this is proarrhythmogenic. Limited data in the literature on the capabilities of speckle tracking echocardiography for assessing proarrhythmogenicity in metabolic syndrome exists. 71 patients with newly diagnosed metabolic syndrome, aged 35–55 years, were studied. Ischemic heart disease was excluded in all patients with stress test cycle ergometry, CT-angiography or selective coronary angiography. All patients underwent a 48-h Holter ECG recording. Based on the latter, they were divided into two groups: 38 patients (53.5%) with a high arrhythmogenic load (supraventricular or ventricular tachycardia, atrial fibrillation/flutter, ventricular extrasystoles over 10%, frequent supraventricular extrasystoles > 500/24 h are included); and 33 patients (46.5%) with low arrhythmogenic load (no significant rhythm disturbances are included). Echocardiography was performed with a GE Vivid T9 emphasizing global longitudinal strain, mechanical dispersion index and left atrium strains. Statistically significant differences in the global longitudinal strain, mechanical dispersion index, and left atrium strain were found between the group with low arrhythmogenicity and the group with high arrhythmogenicity (p < 0.0001). The index of mechanical dispersion has the most optimal sensitivity and specificity of all investigated echocardiographic markers. These results support the mechanical dispersion index as an additional tool for assessing proarrhythmogenicity in metabolic syndrome.

Inflammation plays a key role in the pathogenesis of type 2 diabetes (T2D) and the associated cardiovascular complication. High-sensitivity C-reactive protein (hsCRP) is a widely used marker of systemic inflammation as well as a predictor of cardiovascular risk. There is increasing evidence that glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, may have effect on hsCRP levels, independent of their effects on glycemic control and body weight loss. This purpose of our study is to explore the effect of semaglutide on hsCRP levels in patients with type 2 diabetes. Additionally, we aimed to determine whether the observed effect of semaglutide on hsCRP is fully mediated by changes in HbA1c and body weight, or whether there is a direct effect suggesting the presence of an independent anti-inflammatory mechanism. The study included 66 outpatients with diagnosed type 2 diabetes undergoing therapy with metformin and/or a sulfonylurea. Semaglutide was added to the existing therapeutic regimen. All participants were followed up for 6 months period. Respectively, at the beginning and at the end of the study, the hsCRP values, some selected indicators of glycemic control as well as the anthropometric measurements were recorded. The mean hsCRP value at baseline was 4.90±1.21 mg/L, while after six-month therapy it dropped to 2.23±2.21 mg/L. The results of the analysis have a good potential to contribute to better understanding of the pleiotropic effects of GLP-1 RAs and support the hypothesis of a direct anti-inflammatory role of semaglutide, which could have clinical significance in the context of cardiometabolic risk management in patients with type 2 diabetes.

Thyroid dysfunction is frequently associated with disturbances of calcium and phosphorus homeostasis. Previous studies on bone and mineral metabolism in women with autoimmune thyroiditis (AIT) and hypothyroidism have conflicting results. The aim of the present work was to study the parameters of calcium-phosphorus metabolism in women with newly diagnosed autoimmune hypothyroidism and to compare them with those of the control group of healthy women. The study included 64 women with newly diagnosed autoimmune hypothyroidism. A comparison was made with the data of 75 age-, BMI- and menopausal state-matched healthy women. FT3, FT4, TSH, TPO-Ab, TG-Ab, total and ionized serum calcium, inorganic phosphate, magnesium, parathyroid hormone (PTH) and 25(OH) vitamin D were studied. Total and ionized calcium were lower in hypothyroid women in the absence of statistically significant difference compared to the controls. Intergroup analysis revealed no differences in serum phosphorus and 25(OH)D levels. Serum magnesium and PTH were significantly higher in hypothyroid group. These results coincide with some of the studies that examine the parameters of bone and mineral metabolism in hypothyroidism. Bone turnover is suppressed due to impaired mobilization of calcium from the bone, leading to decreased serum calcium levels and elevated PTH. We found a significant effect of thyroid hormones on magnesium homeostasis. The study did not find differences in vitamin D status between the groups. The observed inverse correlation between 25(OH)D and TgAb supports the concept of pathogenic relationship between vitamin D and the development of AIT.

Chemerin and resistin are adipokines studied as potential markers for early diagnosis and disease severity in patients with knee osteoarthritis (KOA) Therefore, we aimed to investigate the associations serum and synovial levels of chemerin and resistin with inflammatory parameters and ultrasonographic scores (US) in KOA individuals. Serum was collected from 28 patients with KOA and synovial fluid was obtained from 16 of them. Another 31 age and sex matched cases with no joint disease were included as healthy controls. Concentrations of chemerin, resistin, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) were determined with ELISA. Erythrocyte sedimentation rate (ESR), C-reactive protein, serum uric acid (UA) were measured in the patients group. Participants with KOA underwent US assessment using the Outcome Measures in Rheumatology (OMERACT) scores. Patients with KOA had statistically significant higher level of serum resistin than healthy controls [11.05 (3.78–24.13) ng/mL and 7.23 (3.83–12.19) respectively, p < 0.001]. A strong correlation was found between serum chemerin and ESR (r = 0.434, p = 0.021), uric acid (r = 0.573, p = 0.001) as well as the US (r=-0.872, p < 0.001). Serum resistin demonstrated significant association with TNF-alpha (r = 0.398, p = 0.044). In conclusion, both chemerin and resistin might contribute to inflammatory changes associated with KOA. Further studies are needed to elucidate their potential role in the pathogenesis of the disease.

Background and Objectives: To answer the research question: “Is prophylactic central neck lymph node dissection (pCNLD) beneficial among differentiated thyroid carcinoma (DTC) patients?” Materials and Methods: This was a retrospective cohort study enrolling DTC patients treated at the University Hospital Kaspela, Bulgaria, from 30 January 2019 to October 2021. The predictor variable was presence of pCNLD (total thyroidectomy with vs. without pCNLD). The main outcome variables were postoperative complications (i.e., vocal cord paralysis, hypoparathyroidism, postoperative bleeding, and adjacent organ injury) and recurrence parameters. Appropriate statistics were computed with the significant level at p ≤ 0.05. Results: During the study period, 300 DTC patients (59.7% with pCNLD; 79.3% females) with an average age of 52 ± 2.8 years were treated. The mean follow-up period of the entire cohort was 45.8 ± 19.1 months. On bivariate analyses, TT with pCNLD, when compared to TT alone, required longer surgical time (mean difference: 9.4 min), caused nearly similar complications (except transient hypothyroidism: p = 0.04; relative risk, 1.32; 95% confidence interval, 1.0 to 1.73), and no significantly different recurrence events, time to recurrence, and recurrent sites. The benefit–risk analyses using the number needed to treat and to harm (NNT; NNH) also confirmed that TT plus pCNLD was not very beneficial in DTC management. Conclusion: The results of this study refute the benefit of pCNLD in DTC patient care with TT. Further well-designed studies in a larger cohort with a longer follow-up period are required to confirm this conclusion.

Thyroid surgery is generally recommended for malignant conditions and for some benign thyroid disorders. Many patients report weight gain after thyroidectomy especially during the first months following surgery. Studies on patients with Graves’ disease treated either with antithyroid drugs or radioiodine confirm that these patients frequently gain weight after restoration of thyroid function. Other studies have also shown that there is considerable weight gain after thyroidectomy for both nodular goiter and thyroid cancer. Transient hypothyroidism during the postoperative period is often thought to be associated with weight gain after thyroidectomy. The role of a number of adipocytokines and their interaction with the thyroid function has been investigated in the pathogenesis of weight changes. Levothyroxine replacement or suppressive therapy after thyroidectomy has a different impact on the metabolic parameters independent of TSH levels. The long-term effects of the impaired T3/T4 ratio are not fully understood as there are no sensitive markers to assess the biological response of target organs and tissues. Future studies are needed to identify such parameters, provide new considerations for the treatment of patients after total thyroidectomy, and help determine individual target hormone levels to ensure a sustained euthyroid state.

The essential biological action of vitamin D is regulation of calcium and phosphorus metabolism and preserving bone health. In recent years there have been reports about the extraskeletal actions of vitamin D and its role in the regulation of immune system. Vitamin D supplementation appears to reduce the incidence of cardiovascular diseases, cancer, and infections and be able to reduce all-cause mortality. Deficiency of vitamin D has been found to correlate with the increased incidence of autoimmune diseases, including type 1 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis. Autoimmune thyroid diseases (AITD), including Graves’ disease, Hashimoto’s thyroiditis are relatively common autoimmune disorders affecting more than 5% of general population. It has been shown that vitamin D receptors (VDR) and 1-alpha hydroxylase are expressed in papillary thyroid cancer and normal thyroid tissue, suggesting local synthesis of 1,25(OH)2D in the thyroid. While VDR gene polymorphism has been found in much research to be associated with AITDs, very few studies have examined the impact of vitamin D deficiency on the incidence of AITDs in humans with conflicting results. This review focuses on the association between vitamin D and autoimmune thyroid diseases and summarizes the results of vitamin D supplementation studies in patients with AITD.