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Purpose: Despite several factors that may have been associated with poor disease-free survival (DFS) in patients with medullary thyroid carcinoma (MTC), only a few studies have evaluated the prognostic factors affecting DFS in MTC patients. Therefore, this study evaluated the prognostic factors affecting DFS, in a large number of patients with MTC., Methods: Patients treated for MTC were retrospectively analyzed. Patients were stratified as having persistent/recurrent disease and no evidence of disease (NOD) at the last follow-up. The factors affecting DFS after the initial therapy and during the follow-up period were investigated., Results: This study comprised 257 patients [females 160 (62.3%), hereditary disease 48 (18.7%), with a mean follow-up time of 66.8 ± 48.5 months]. Persistent/recurrent disease and NOD were observed in 131 (51%) and 126 (49%) patients, respectively. In multivariate analysis, age > 55 (HR: 1.65, p = 0.033), distant metastasis (HR: 2.41, p = 0.035), CTN doubling time (HR: 2.7, p = 0.031), and stage III vs. stage II disease (HR 3.02, p = 0.048) were independent predictors of persistent/recurrent disease. Although 9 (8%) patients with an excellent response after the initial therapy experienced a structural recurrence, the absence of an excellent response was the strongest predictor of persistent/recurrent disease (HR: 5.74, p < 0.001)., Conclusions: The absence of an excellent response after initial therapy is the strongest predictor of a worse DFS. However, a significant proportion of patients who achieve an excellent response could experience a structural recurrence. Therefore, careful follow-up of patients, including those achieving an excellent response is essential., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Takayasu's arteritis (TAK) is a chronic inflammatory large vessel vasculitis with a grim prognosis due to the excessive risk for cardiovascular (CV) diseases. Its diagnosis relies on radiographic imaging and its differentiation particularly from atherosclerosis could be challenging. Hypothesising that vascular morphology observed in TAK would be comparable to that found in type 2 diabetes mellitus (T2DM), a prototype for advanced atherosclerosis, we compared two disease groups using carotid artery B mode US and shear wave elastography (SWE)., Methods: A total of 72 patients with TAK (63F/9M; mean age: 42.7± 10.0 years) and 74 patients with T2DM (65F/9M; mean age: 50.2± 7.1 years) were studied. Intima-media thickness (IMT), outer diameter and arterial stiffness as assessed by SWE values were measured on the common carotid artery (CCA) and atherosclerotic plaques were recorded. Clinical characteristics, CV risk factors and previous history of CV diseases were determined. Framingham risk score was calculated., Resuults: Patients with TAK exhibited significantly lower atherosclerotic risk but higher systolic blood pressure (BP) levels compared to those with T2DM. The mean values of CCA IMT, outer diameter, and stiffness were significantly elevated among patients with TAK compared to those with T2DM. Carotid artery plaques were evenly distributed between the study groups, but their anatomical localisation and composition differed significantly. While coronary artery disease (CAD) was more prevalent among T2DM patients, cerebrovascular diseases were more frequent among TAK patients., Conclusions: Our study revealed distinctive vascular alterations and atherosclerotic changes when compared to advanced atherosclerosis associated with T2DM. Apart from these, higher levels of systolic BP and significantly different distribution of CV diseases between TAK and T2DM also suggest that TAK should be handled with distinct assessment strategies than that employed in conventional atherosclerotic conditions.

Aim: To investigate the relationship of serum lipoprotein(a) [Lp(a)] and other serum lipids with presence of Graves' ophthalmopathy (GO). Methods: A total of 99 consecutive patients diagnosed with Graves' disease (GD), aged 18-65 years, who had not received prior treatment for GO, thyroid surgery, or radioactive iodine therapy, were recruited between June 2020 and July 2022. In addition, 56 healthy controls (HCs) were included as the control group. All patients underwent an ophthalmological examination, and were classified based on the presence of GO into the GO group ( n  = 45) and no GO group ( n  = 54). Fasting blood samples were collected from all participants to analyze serum lipid parameters, including Lp(a), total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. Results: The median serum levels of Lp(a) were 5.7 [4.3-9.2] in the GO group, 6.7 [3.7-9.9] in the no GO group, and 4.7 [3-7.6] in the HC group. The intergroup comparisons of serum Lp(a) levels showed no significant result. The serum levels of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were also similar between the groups ( P  > 0.05 for all). However, when analyzing only euthyroid GD patients and the control group, the serum LDL cholesterol levels were found to be significantly higher in the euthyroid GO group [median: 132 interquartile range (IQR) (110-148) mg/dL] than in the HCs [median: 96 IQR (94-118) mg/dL] ( P  = 0.002). Conclusion: The findings of our study did not support the association between serum Lp(a) levels and GO.

In this study, we aimed to reveal the pro-inflammatory effects of serum 25-hydroxyvitamin D3 (Vit D) deficiency and insufficiency in new-onset type 2 diabetes mellitus (T2DM) and prediabetes. We recruited 84 prediabetes patients, 94 new-onset T2DM patients and 113 healthy participants. We measured the levels of C-reactive protein (CRP), fibrinogen, ferritin, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) in the serum of the participants. ANOVA Bonferroni and Kruskal-Wallis Dunn tests were used to compare the inflammation markers and vitamin D levels between the groups. Based on covariance analysis with age, gender and BMI, the Vit D levels of the T2DM group were significantly lower ( p < 0.003). Pro-inflammatory markers and CRP were significantly higher in prediabetic and diabetic subjects. In the prediabetes group, IL-1β, IL-6, IL-8, TNF-α and MAPK were significantly higher in those with Vit D insufficiency and deficiency groups. In the T2DM group, IL-1β, IL-6, IL-8, TNF-α, NF-κB, MAPK and CRP were significantly higher in those with Vit D insufficiency and deficiency. Our study emphasizes the pro-inflammatory effects of Vit D deficiency and insufficiency in new-onset type 2 diabetes mellitus and prediabetes.

Purpose: This study aimed to investigate the long-term effects of radioiodine treatment (RAI) on blood cell counts in patients with differentiated thyroid cancer (DTC) and to describe the characteristics of patients at high risk for blood cell count abnormalities., Methods: The study included patients with DTC who underwent RAI treatment between 2007 and 2017. Patients with regular complete blood counts for at least 5 years were included, while those with diseases or treatments that could influence blood count parameters were excluded. Blood cell count abnormalities were defined according to the Common Terminology Criteria for Adverse Events version 5.0, and factors influencing these abnormalities were examined., Results: A total of 225 patients were analyzed. The mean age at diagnosis was 45.8 ± 13.9 years, and 76.5% of patients were female. In the first year after RAI, leukocyte, neutrophil, and lymphocyte counts were significantly reduced compared with baseline values. The leukocyte and neutrophil counts returned to baseline values by the third year, while the decrease in lymphocytes continued until the fifth year. Blood cell count abnormalities developed in 16 patients (7.1%) within the first year after RAI. Risk factors for blood cell count abnormalities within the first year after RAI included male sex, older age, T4, N1, and M1 disease, as well as higher RAI doses. In logistic regression analysis, only RAI dose remained independently associated with blood cell count abnormalities., Conclusion: These results suggest an association between RAI dose and blood cell count abnormalities, characterized by mild lymphopenia, and indicate that the risk of mild lymphopenia persists over time. Careful consideration should be given when planning high-dose RAI for patients at a high risk of blood cell count abnormalities, such as males with metastatic disease and of advanced age., (© 2023. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Purpose: To investigate the prevalence of microalbuminuria and factors associated with microalbuminuria in Graves' Disease (GD)., Methods: This cross-sectional and single-center study included 99 patients with GD and 47 healthy controls (HC). Exclusion criteria such as active infection, uncontrolled diabetes, and chronic kidney disease were applied to the participants. The participants' clinical findings, comorbidities, drug use, laboratory tests, and thyroid antibody levels were recorded. Spot urine samples were collected and stored at - 80 ℃ to analyze the presence of microalbuminuria., Results: The prevalence of microalbuminuria in patients with GD was 12.1%. The median microalbumin/creatinine ratio in spot urine (UACR) in patients with GD (9.49 mg/g [5.09-18.10]) was higher than in the HC group (7.99 mg/g [3.48-12.88], p = 0.033). UACR was correlated with thyroid-stimulating hormone receptor antibody (TRAb), thyroid-stimulating hormone (TSH), and free triiodothyronine (FT3) levels (p = 0.020, p = 0.006, p = 0.009 respectively). In the regression analysis, only the relationship between TRAb level and UACR remained (p = 0.040)., Conclusion: This study demonstrates an increased prevalence of microalbuminuria in patients with GD. There was a significant correlation between microalbuminuria and TRAb level in patients with GD. This relationship suggests that one of the underlying mechanisms of microalbuminuria seen in patients with GD may be autoimmunity., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The study is an investigation of aggressive tumor features, prognosis, and disease-specific mortality rates of differentiated thyroid cancer (DTC) in the presence of concomitant Hashimoto's Thyroiditis (HT). The data of patients with DTC followed in our tertiary care center between 2000-2022 were analyzed. Variables such as patient age, gender, preoperative serum autoantibody levels, tumor characteristics, and treatment modalities were obtained from medical records. The diagnosis of HT was based either on the presence of a positive result in the pathological examination and/or on antibody positivity. A total of 637 patients [mean±SD age, 44.9±13.5 years; 485 women [76.1%)] were included in the analysis. The overall prevalence of coexistent HT was 22.9% (n=146). The disease-specific mortality associated with DTC was 2.9%. DTC patients with HT compared to those without; have more positive lymphovascular invasion (p<0.001), and lymph node metastases (p<0.001). According to the Kaplan-Meier curves, disease-specific survival rates among DTC patients without HT were significantly higher than patients with HT (log-rank p=0.002). The disease-specific mortality rate was 4.79% in DTC patients with HT, it was 1.43% in those without HT. Hashimoto thyroiditis was not associated with a 10-year recurrence-free survival (p=0.059). Differentiated thyroid cancers with concomitant HT are associated with some aggressive tumor features (such as lymphovascular invasion and nodal metastasis) and lower survival. In staging systems based on tumor risk factors, it may be useful to evaluate the presence of concomitant HT as a prognostic factor., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The outbreak of COVID-19 has affected more than half a billion people worldwide and caused more than 6 million deaths since 2019. The responsible virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affects the lungs, but it has multisystemic effects. It is well known that dysfunction of multiple endocrine organs may occur during or after COVID-19. Impairment of the hypothalamic-pituitary-adrenal (HPA) axis is of utmost importance as it may lead to death if went undiagnosed. SARS-CoV-2 may cause both primary and secondary adrenal insufficiencies (AIs). The clinical manifestations of AI are generally non-specific and might be attributed to the complications caused by the infection itself. The underlying pathogenetic mechanisms were explained by the immunogenic, vascular effects of the infection or the direct effects of the virus. The diagnosis of AI in critically ill patients with COVID-19 is not straightforward. There is lack of consensus on the cut-off values of basal serum cortisol levels and stimulation tests during the disease. Here we review the literature with a special regard on the evaluation of the HPA axis in patients with COVID-19. We conclude that the possibility of AI should always be kept in mind when dealing with patients with COVID-19, and repeated basal cortisol measurements and the ACTH stimulation test results could guide the clinician during the diagnostic process., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: In this single-center study, we analyzed a retrospective cohort of patients with diabetic foot infections (DFIs) between 2011 and 2020. Patients and Methods: The first and second five-year periods were compared. A poor prognosis was defined as a primary composite end point including re-infection, major amputation, or mortality at six months. Results: A total of 484 patients were enrolled. Overall, 269 patients had the primary composite end point. A substantial decrease was detected in the second five-year period in terms of re-infection (n = 132, 66.0% vs. n = 68, 23.9%; p < 0.001) and mortality (n = 22, 11.0% vs. n = 7, 2.5%; p < 0.001). A total of 798 micro-organisms were isolated from 484 patients. A substantial increase was detected in polymicrobial infections (48.5% vs. 65.1%; p = 0.001) as well as Streptococcus spp. (2.5% vs. 9.2%; p = 0.003), Corynebacterium spp. (9.5% vs. 22.9%; p < 0.001), and extended-spectrum β-lactamase (ESBL) producing Escherichia coli (3.0% vs. 12.7%; p < 0.001) in the second five-year period, whereas the prevalence of multi-drug-resistanct (MDR) Pseudomonas aeruginosa (17.0% vs. 10.2%; p = 0.029) and carbapenem-resistant Acinetobacter baumannii (7.5% vs. 2.8%; p = 0.017) decreased. Multivariable regression analysis revealed that MDR Pseudomonas aeruginosa (odds ratio [OR], 1.917; 95% confidence interval [CI], 1.074-3.420; p = 0.028) and carbapenem-resistant Acinetobacter baumannii (OR, 3.069; 95% CI, 1.114-8.453; p = 0.030) were independent predictors for poor prognosis. Conclusions: This 10-year cohort study provides reassuring information about the changing epidemiology of DFIs and the prognostic determinants in patients with DFIs.

Background: The aim of this study was to investigate the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on the glomerulus through the evaluation of podocyturia in patients with diabetic kidney disease (DKD)., Methods: The study population was composed of 40 male patients with type 2 diabetes mellitus; 22 of them received SGLT2i (SGLT2i group), and the others who did not were the control. The DKD-related parameters of patients were monitored before SGLT2i initiation, and then in the third and sixth month of the follow-up period. Patients' demographic, clinical, laboratory, and follow-up data were obtained from medical charts. Microalbuminuria was measured in 24-h urine. The number of podocytes in the urine was determined by immunocytochemical staining of two different markers, namely podocalyxin (podx) and synaptopodin (synpo). Concentrations of urine stromal cell-derived factor 1a and vascular endothelial growth factor cytokines were quantified with an enzyme-linked immunosorbent assay kit., Results: At the end of the follow-up period, decreases in glycosylated hemoglobin, glucose, systolic and diastolic blood pressure, uric acid level, and microalbuminuria, and improvement in body mass index level and weight loss were significant for the SGLT2i group. On the other hand, there was no significant difference in terms of these parameters in the control group. The excretion of synaptopodin-positive (synpo + ) and podocalyxin-positive (podx + ) cells was significantly reduced at the end of the follow-up period for the SGLT2i group, while there was no significant change for the control., Conclusions: At the end of the follow-up period, male patients receiving SGLT2i had better DKD-related parameters and podocyturia levels compared to baseline and the control group. Our data support the notion that SGLT2i might have structural benefits for glomerular health., (© 2022 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

SARS-CoV-2 may affect the hypothalamic-pituitary axis and pituitary dysfunction may occur. Therefore, we investigated neuroendocrine changes, in particular, secondary adrenal insufficiency, using a dynamic test and the role of autoimmunity in pituitary dysfunction in patients with COVID-19. The single-center, prospective, case-control study included patients with polymerase chain reaction (PCR)-confirmed COVID-19 and healthy controls. Basal hormone levels were measured, and the adrenocorticotropic hormone (ACTH) stimulation test was performed. Antipituitary (APA) and antihypothalamic antibodies (AHA) were also determined. We examined a total of 49 patients with COVID-19 and 28 healthy controls. The frequency of adrenal insufficiency in patients with COVID-19 was found as 8.2%. Patients with COVID-19 had lower free T 3 , IGF-1, and total testosterone levels, and higher cortisol and prolactin levels when compared with controls. We also demonstrated the presence of APA in three and AHA in one of four patients with adrenal insufficiency. In conclusion, COVID-19 may result in adrenal insufficiency, thus routine screening of adrenal functions in these patients is needed. Endocrine disturbances in COVID-19 are similar to those seen in acute stressful conditions or infections. Pituitary or hypothalamic autoimmunity may play a role in neuroendocrine abnormalities in COVID-19., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: During the COVID-19 pandemic, health care systems are under extreme pressure. This study analyzed health care resource use (HCRU) and costs in patients admitted to the hospital for COVID-19 and aimed to estimate the one-year direct medical cost of the disease in Turkey., Methods: This retrospective cohort study was conducted between March and July 2020 in a tertiary hospital (n = 1056) in Istanbul. Patient demographics, clinical and treatment characteristics at admission, comorbidities, disease severity, and costs from a payer perspective were evaluated using the microcosting method. The results include LOS, hospital costs, and univariate and generalized linear models to investigate influencing factors. The data were extrapolated to provide a country-level estimate., Results: The mean length of stay was 9.1 days (SD 6.9). The mean length of stay was 8.0 days (4.7) for patients hospitalized in wards versus 14.8 days (SD 12.0) for patients hospitalized in the ICU. In univariate analysis, several factors, including O 2 therapy (+ 3.7 days), high CRP > 41.8 mg/L (+ 3.8 days), and elevated ferritin (+ 3.5), were found to be associated with a longer LOS (p < 0.05). The direct annual medical cost of COVID-19 was estimated at PPP$ 2.1 billion. The COVID-19 pandemic resulted in a direct medical burden that corresponds to 2.0% of the government health expenditures and 0.8 per thousand of Turkey's gross domestic product (GDP)., Conclusions: Estimating the impact of this pandemic in terms of HCRU and costs to the health care system can help design strategies to manage the pandemic., (© 2021. The Author(s).)

Introduction: This study aims to evaluate the cost-effectiveness of remdesivir compared to other existing therapies (SoC) in Turkey to treat COVID-19 patients hospitalized with < 94% saturation and low-flow oxygen therapy (LFOT) requirement., Methods: We compared remdesivir as the treatment for COVID-19 with the treatments in the Turkish treatment guidelines. Analyses were performed using data from 78 hospitalized COVID-19 patients with SpO 2  < 94% who received LFOT in a tertiary healthcare facility. COVID-19 episode costs were calculated for 78 patients considering the cost of modeled remdesivir treatment in the same group from the payer's perspective. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) was calculated for remdesivir versus the SoC for the population identified. For Turkey, a reimbursement threshold value between USD 8599 (1 × per capita gross domestic product-GDP) and USD 25.797 (3 × GDP) per QALY was used., Results: In the remdesivir arm, the length of hospital stay (LOS) was 3 days shorter than the SOC. The low ventilator requirement in the remdesivir arm was one factor that decreased the QALY disutility value. In patients who were transferred to intensive care unit (ICU) from the ward, the mean LOS was 17.3 days (SD 13.6), and the mean cost of stay was USD 155.3/day (SD 168.0), while in patients who were admitted to ICU at baseline, the mean LOS was 13.1 days (SD 13.7), and the mean cost of stay was USD 207.9/day (SD 133.6). The mean cost of episode per patient was USD 3461.1 (SD 2259.8) in the remdesivir arm and USD 3538.9 (SD 3296.0) in the SOC arm. Incremental QALYs were estimated at 0.174. Remdesivir treatment was determined to be cost saving vs. SoC., Conclusions: Remdesivir, which results in shorter LOS and lower rates of intubation requirements in ICU patients than existing therapies, is associated with higher QALYs and lower costs, dominating SoC in patients with SpO 2  < 94% who require oxygen support., (© 2021. The Author(s).)

Background: To investigate the relationship between visceral adiposity index (VAI) and other metabolic syndrome (MetS)-related parameters, and thyroid nodules. Methods: This single-center, prospective, case-control study included 67 patients with thyroid nodules and 48 healthy volunteers with similar age, sex, and body mass index (BMI). Biochemical parameters were obtained from medical charts. Anthropometric measurements and total body composition analysis were performed to calculate VAI and other MetS parameters. The parenchymal structure was evaluated according to VESINC (Volume, Echogenicity, Sonographic texture, Infiltration of pseudonodular Nodules, Cysts) system on thyroid ultrasound and nodule characteristics were also detected. MetS was defined according to International Diabetes Federation criteria. Results: We examined a total of 67 patients with thyroid nodule and 48 healthy volunteers. Sixty-one (91%) were female in the patient group; and 43 (90%) were female in the control group. The mean age was 48.5 ± 11.6 years in the patient group; 47.2 ± 9.5 years in the control. The median VAI was significantly higher in the patient group than the control group [4.1 interquartile range (IQR: 2.6-5.9) vs. 3 (IQR: 2-4.3), P  = 0.024]. There was a positive correlation between VAI and BMI, waist/hip ratio (WHpR), waist/height ratio (WHtR), and homeostasis of model assessment of insulin resistance (HOMA-IR). On the other hand, there was no significant correlation between VAI and thyroid function tests and autoantibodies and thyroid volume. Conclusions: In conclusion, we demonstrated that MetS was more common in patients with thyroid nodules. Although VAI and HOMA-IR levels were significantly different between the two groups, we found no significant difference in terms of waist circumference, WHpR, and WHtR. This might suggest that VAI compared with these parameters, better predicts the risk of MetS in patients with thyroid nodules.

Type 2 diabetes (T2D) is a complicated public health problem in Turkey as well as worldwide. Genome-wide approaches have been guiding in very challenging situations, such as the elucidation of genetic variations underlying complex diseases such as T2D. Despite intensive studies worldwide, few studies have determined the genetic susceptibility to T2D in Turkish populations. In this study, we investigated the effect of genes that are strongly associated with T2D in genome-wide association (GWA) studies, including MTNR1B, CDKAL1, THADA, ADAMTS9 and ENPP1, on T2D and its characteristic traits in a Turkish population. In 824 nonobese individuals (454 T2D patients and 370 healthy individuals), prominent variants of these GWA genes were genotyped by real-time PCR using the LightSNiP Genotyping Assay System. The SNP rs1387153 C/T, which is located 28 kb upstream of the MTNR1B gene, was significantly associated with T2D and fasting blood glucose levels (P < 0.05). The intronic SNP rs10830963 C/G in the MTNR1B gene was not associated with T2D, but it was associated with fasting blood glucose, HbA1C and LDL levels (P < 0.05). The other important GWA loci investigated in our study were not found to be associated with T2D or its traits. Only the SNP rs1044498 (A/C variation) in the ENPP1 gene was determined to be related to fasting blood glucose (P < 0.05). Our study suggests, consistent with the literature, that the MTNR1B locus, which has a prominent role in glucose regulation, is associated with T2D development by affecting blood glucose levels in our population.

Introduction: The aim of this was to describe the predictors of mortality related to COVID-19 infection and to evaluate the association between overweight, obesity, and clinical outcomes of COVID-19., Methods: We included the patients >18 years of age, with at least one positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction. Patients were grouped according to body mass index values as normal weight <25 kg/m2 (Group A), overweight from 25 to <30 kg/m2 (Group B), Class I obesity 30 to <35 kg/m2 (Group C), and ≥35 kg/m2 (Group D). Mortality, clinical outcomes, laboratory parameters, and comorbidities were compared among 4 groups., Results: There was no significant difference among study groups in terms of mortality. Noninvasive mechanical ventilation requirement was higher in group B and D than group A, while it was higher in Group D than Group C (Group B vs. Group A [p = 0.017], Group D vs. Group A [p = 0.001], and Group D vs. Group C [p = 0.016]). Lung involvement was less common in Group A, and presence of hypoxia was more common in Group D (Group B vs. Group A [p = 0.025], Group D vs. Group A [p < 0.001], Group D vs. Group B [p = 0.006], and Group D vs. Group C [p = 0.014]). The hospitalization rate was lower in Group A than in the other groups; in addition, patients in Group D have the highest rate of hospitalization (Group B vs. Group A [p < 0.001], Group C vs. Group A [p < 0.001], Group D vs. Group A [p < 0.001], Group D vs. Group B [p < 0.001], and Group D vs. Group C [p = 0.010])., Conclusion: COVID-19 patients with overweight and obesity presented with more severe clinical findings. Health-care providers should take into account that people living with overweight and obesity are at higher risk for COVID-19 and its complications., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Background/aim: Diabetic nephropathy (DN) is one of the most serious microvascular complications in diabetic patients. The kruppel-like transcription factor-4 (KLF-4) affects the expression of genes involved in the pathogenesis of DN. The present study aims to identify the KLF-4 expression and DNA methylation (DNAMe) status in patients with type-2 diabetes (T2D) and DN and to reveal the contribution of the KLF-4 to the development of DN., Material and Methods: The cohort study was performed with blood samples from 120 individuals; T2D group (n = 40), DN group (n = 40) and control group (n = 40). The expression level of the KLF-4 gene was analyzed using the real-time polymerase chain reaction (qRT-PCR) and the methylation profile detected using the methylation-specific PCR (MS-PCR) technique., Results: According to our findings, KLF-4 mRNA expression in the T2D group was 1.60 fold lower than in the control group (p = 0.001). In the DN group, the expression of KLF-4 mRNA was 2.92-fold less than that of the T2D group (p = 0.001). There was no significant alteration in the DNAMe status among the groups., Conclusion: Our findings showed that regardless of the DNAMe status, KLF-4 gene expression may play a role in the development of T2D and DN. This suggests that the KLF-4 gene may be the target gene in understanding the mechanism of nephropathy, which is the most important complication of diabetes, and planning nephropathy-related treatments, but the data should be supported with more studies., (Copyright © 2019 IMSS. Published by Elsevier Inc. All rights reserved.)

Purpose: Insulin resistance (IR) and increased oxidative stress (OS) are the characteristics of polycystic ovary syndrome (PCOS). In this study, we aimed to evaluate the effects of oral glucose tolerance (OGTT) and mixed meal tests (MMT) on plasma total oxidant (TOS) and total antioxidant status (TAS) in patients with PCOS and the relationship between these parameters and IR, calculated via homeostasis of model assessment-IR (HOMA-IR) and Matsuda's insulin sensitivity index (ISI) derived from OGTT and MMT., Methods: Twenty-two patients with PCOS, and age- and body mass index (BMI)-matched 20 women as controls were enrolled into the study. Five-hour OGTT and MMT were performed on different days, and before and after these tests, plasma TOS and TAS levels were investigated. IR was calculated with HOMA-IR and Matsuda's ISI., Results: HOMA-IR levels were higher in patients with PCOS, compared to controls, while Matsuda's ISI derived from OGTT and MMT was higher in controls. Plasma TOS levels before OGTT and MMT were higher in patients with PCOS than controls, while TAS levels were similar. After OGTT, plasma TOS levels became decreased at 5th hour, when compared to baseline values in PCOS group. Likewise, the same decrement was found in controls, but the decrement was not significant. After OGTT and MMT at 5th hour, no changes were observed in TAS levels, compared to baseline., Conclusion: Matsuda's ISIs derived from OGTT and MMT can be used instead of each other, and interestingly, we found a decrease in TOS levels after OGTT in patients with PCOS.

Objective. Diabetes mellitus (DM) is associated with low-grade inflammation. The benefits of regular exercise for the DM are well established, whereas less is known about the impact of aerobic exercise on malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) in the DM. Methods. We randomised 64 participants, who do not exercise regularly, without any diabetic chronic complications in parallel to 12 weeks of aerobic exercise (three times per week, n = 31) and no exercise (control; n = 33). Plasma levels of soluble TNF-α and MDA levels were measured before-after physical training programme and control group. Results. Sixty-four patients with type 2 diabetes mellitus were analysed. When comparing the two groups of patients with age, gender, hemoglobin A1c (HbA1c) levels, lipid profile, waist circumference, body mass index (BMI) and class of treatment for diabetes were not different between groups. While soluble TNF-α remained essentially unaffected by physical training, plasma concentrations of MDA markedly decreased (P < 0.05); physical training also decreased body weight, waist circumference, and blood pressure (P < 0.05). Conclusion. Exercise training favorably affected body weight, waist circumference, and blood pressure. A three-weekly, 12-week, aerobic-training programme, without a concomitant weight loss diet, was associated with significant decrease in MDA levels in type 2 diabetic individuals.

Adiponectin, an adipose tissue specific protein encoded by the Adiponectin gene, modulates insulin sensitivity and plays an important role in regulating energy homeostasis. Many studies have shown that single nucleotide polymorphisms (SNPs) in the Adiponectin gene are associated with low plasma Adiponectin levels, insulin resistance and an increased risk of type 2 diabetes mellitus. The aim of the present study was to evaluate the contribution of the Adiponectin gene polymorphisms in genetic background of type 2 diabetes in a Turkish population. In total, 169 unrelated and non-obese diabetic patients and 119 age- and BMI-matched nondiabetic individuals with no family history of diabetes were enrolled in this study. We detected a significant association between type 2 diabetes and two SNPs: SNP −11391G N A, which is located in the promoter region of the Adiponectin gene, and SNP +276G N T, which is found in intron 2 of the gene (P b 0.05). The silence SNP G15G (+45TN G) in exon 1 and SNP+349ANG in intron 2 also showed a weak association with type 2 diabetes (P=0.06 and P=0.07, respectively),while SNPs−3971ANG in intron 1 and Y111H, R112C and H241P in exon 3 showed no association (P N 0.05). In conclusion, these findings suggest that Adiponectin gene polymorphisms might be effective on susceptibility for type 2 diabetes development which emerged from the interactions between multiple genes, variants and environmental factors.

Objective: The aim of this study was to examine the current prevalence of major depression and anxiety disorders in patients with euthyroid Hashimoto's thyroiditis (HT) and euthyroid goiter., Method: The study sample was formed by consecutive 51 and 45 patients who were admitted to the endocrinology outpatient clinic and diagnosed with euthyroid HT and endemic/nonendemic goiter, respectively, and 68 healthy controls. Current diagnoses of psychiatric disorders were determined using the Structured Clinical Interview for DSM-IV. Beck Depression Inventory and Beck Anxiety Inventory were applied to the participants., Results: There was a statistically significant difference among the three groups in terms of major depression (P=.001), any mood or anxiety disorder (P=.000), any depressive disorder (P=.020), any anxiety disorder (P=.016) and obsessive-compulsive disorder (OCD) (P=.013). In the HT group, the prevalence of depression (P=.000), OCD (P=.005) and panic disorder (P=.041) was significantly higher than that in the control group. In the goiter group, depression (P=.006), any depressive disorder (P=.03), and any mood or anxiety disorder (P=.000) were significantly common in comparison to the control group. No significant difference was found between the HT and goiter groups., Conclusions: Euthyroid HT and euthyroid goiter increase predisposition to major depression and anxiety disorders, and thyroid autoimmunity and other thyroid pathologies should be investigated in euthyroid patients with chronic and treatment-resistant complaints., (© 2014.)

Primary ovarian insufficiency (POI) is not only a gynecological problem but also has serious effects on women's health such as changes in hormone levels that can trigger fluctuations in blood sugar level and inflammation status. The present study was designed to determine vitamin D, copper, zinc, metabolic parameters [insulin, homeostasis model of assessment-insulin resistance (HOMA-IR)], inflammation parameters such as procalcitonin and high sensitivity C reactive protein (hs-CRP), and lipid profile in POI patients and control subjects with normal menstrual cycles. A total of 43 patients with nondiabetic POI were studied in order to evaluate and compare the findings with those of the control group, which comprised 33 women with normal menstrual cycles. The women with POI had higher levels of serum copper, serum insulin, glucose, LDL-cholesterol, total cholesterol, HOMA-IR, hs-CRP, and procalcitonin, whereas serum vitamin D and zinc levels were lower compared with the healthy control group. Follicle-stimulating hormone (FSH) levels were positively correlated with insulin, glucose, HOMA-IR, hs-CRP, procalcitonin, and copper and negatively correlated with vitamin D and zinc levels. In multivariate statistic analyses with body mass index and FSH as dependent variables, FSH was positively associated with copper and HOMA-IR negatively with vitamin D levels. The present study demonstrated that women with POI have traditional risk factors for diabetes mellitus, including lower levels of vitamin D, whereas higher levels of copper and HOMA-IR.

Objective: Premature menopause in young women is associated with an increased incidence of cardiovascular disease. The present study was designed to determine vitamin D (vit D) and the coagulation parameters such as activated partial thromboplastin time (APTT), PT, D-dimer, white blood cell (WBC), and mean platelet volume (MPV) levels, in primary ovarian insufficiency (POI) patients and control women with a normal menstrual cycle., Materials and Methods: A total of 43 patients with non-diabetic POI were studied in order to evaluate and compare with the control group comprising 33 women with a normal menstrual cycle., Results: There was no significant difference between the groups for age and body mass index (BMI). D-dimer, WBC, MPV, PT, total cholesterol, and LDL cholesterol were higher in women with POI. APTT levels were also increased but missed the significance in POI group. Women with POI had significantly lower serum vit D levels compared with healthy control group. FSH level was positively correlated with D-dimer, WBC, MPV, and negatively correlated to vit D and serum D vit level was inversely correlated with MPV, APTT, D-dimer, FSH levels in individual women., Conclusions: The obtained results seem to indicate that POI patients had low-grade systemic coagulation and fibrinolytic activation as evidenced by elevated D-dimer, WBC, MPV, PT values potentially be used as indicators of risk factor for thrombosis and atherosclerosis in POI women. All of our patients with POI were deficient in vit D. These results also suggest that vit D deficiency plays important roles of POI women and associated with coagulation, independently from age and BMI.

We recently encountered a 35-year old man who suffered from frequent hypoglycemia. His blood test revealed the presence of high and suppressed level of insulin with supressed C-peptide levels, hypothalamic-pituitary axis was normal response in hypoglycemia and negative for anti-insulin antibody. Endocrinological and imaging data eliminated the possibility of insulinoma. His symptoms responded well to the therapy of prednisolone (60 mg/day) and plasmapheresis. We followed up the patient over the subsequent 6 months without remarkable lesions. He has had no further recurrences of hypoglycemia. We believe that the antiinsulin receptor antibody might have induced hypoglycemia in this patient., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background and Aims: ATP-sensitive potassium (K(ATP)) channels of pancreatic β-cells play a key role in glucose-stimulated insulin secretion mechanism. The Kir6.2 protein, forming the K(ATP) channel pore inwardly, and the SUR1 protein that surrounds it forming the outside part of the channel were encoded by ABCC8 and KCNJ11 genes, respectively. Recent studies reported that the single nucleotide polymorphisms (SNPs) established in these genes are associated with defects in insulin secretion and type 2 diabetes mellitus (T2DM). We aimed to investigate the allele profiles and the risk alleles of the ABCC8 and KCNJ11 genes and to highlight the associations with the disease in patients in Konya region of Turkey where T2DM is common., Methods: In this study, 169 patients with T2DM and 119 healthy controls were included. A total of 29 SNPs in ABCC8 and KCNJ11 genes were screened by PCR-SSCP technique and sequenced. Biochemical parameters and genotype-phenotype relationships were analyzed using variance analysis., Results: R1273R silent substitution in exon 31 and 16/-3t→c substitution in noncoding region of exon 16 of ABCC8 gene showed a significant association (OR 4.8 [95% CI 2.41-9.77], p <0.001 and OR 3.5 [95% CI 1.64-7.40], p <0.001 under dominant and recessive models, respectively). We detected a significant association between E/K heterozygote genotype and reduced plasma insulin level in patients with T2DM (p <0.05)., Conclusions: ABCC8 exons 16 and 31 variants increase susceptibility to T2DM and KCNJ11 E23K decreases insulin secretion in a Turkish population., (Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.)

A 41-year-old man with a history of hyperthyroidism had been treated with methimazole and propranolol for the past 2 months. He developed multiorgan dysfunction with acute liver failure, severe lactic acidosis, disseminated intravascular coagulation, heart failure and acute pulmonary edema with rapid deterioration of renal function. The patient had no history of alcoholism, drug abuse, blood transfusion, or exposure to hepatitis A, B, or C. Extrahepatic obstruction was ruled out with an abdominal ultrasonogram. Serologic studies and immunologic tests were negative. This case illustrates the sudden and abrupt deterioration of multiorgan dysfunction due to antithyroid drug administration and thyroid storm. The thyroid storm score of Burch and Wartofsky was 90/140. The multiorgan dysfunction was reversed by discontinuation of the methimazole and treat with hemodialysis, steroids, cholestyramine, nonselective beta-blocker, fresh frozen plasma infusion and supportive management in the intensive care unit. The patient was discharged from the hospital with normal coagulation parameters, renal and liver function tests., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Aim. Colonic polyps and thyroid nodules are common diseases and their frequency increases with age. In the literature, there is no study investigating the coexistence of colonic polyps and thyroid nodules. Therefore, this study was designed to investigate thyroid nodule prevalence in patients with colonic polyps. Material and Methods. Sixty-six patients with colonic polyps and 146 patients without colonic polyps enrolled into the study. Age and sex matched control group was composed from patients without colonic polyps. Colonoscopic examinations, thyroid ultrasonographies were performed in all patients, and TSH were measured. Results. Male/female ratio in polyp and control groups were 40/26 versus 68/78, respectively (P = 0.058). Mean ages were similar in both groups (53.3 ± 11.4 versus, 51.8 ± 11.4, P = 0.373). Thyroid nodule was detected in 44 (66.7%) patients with polyps and in 61 (41.8%) controls (P = 0.001). Patients with adenomatous polyps had 5 or more thyroid nodules compared to patients with hyperplastic polyps (P = 0.03). Thyroid nodules were more prevalent among patients aged 50 or older compared to 50 years or less (P = 0.023). Conclusion. Thyroid nodules were detected more common in patients with colonic polyps. Further studies are needed to clarify this coexistence.

Background: Increased levels of selectins, adhesion molecules, hs-CRP and homocysteine are considered important as indicators of atherosclerosis. There is a significant amount of evidence that high LDL-C levels are a risk factor for coronary artery disease, whereas the relevance of isolated triglycerides is controversial. The present study aims to compare the levels of homocysteine, hs-CRP, E-selectin, sP-selectin, VCAM-1, ICAM-1 in patients with isolated hypertriglyceridemia and polygenic hypercholesterolemia., Methods: The following three groups were formed: polygenic hypercholesterolemia group (n=30), isolated hypertriglyceridemia group (n=30) and control group (n=30). These three groups were matched in terms of BMI, waist circumference and gender. Plasma high sensitive CRP, homocysteine, sVCAM-1, sICAM-1, sP-selectin, sE-Selectin levels of patients in these three groups were measured., Results: In the present study, mean values for sE-selectin, sVCAM-1 and sICAM-1 in the polygenic hypercholesterolemia group were significantly higher than in the other two groups (p<0.001). Homocysteine and hs-CRP levels were higher in the polygenic hypercholesterolemia group, compared to the isolated hypertriglyceridemia group (p=0.019, p<0.001; respectively) and the control group (p<0.001, p<0.001; respectively). Comparison of patients with hypertriglyceridemia to individuals in the control group did not yield a significant difference in terms of sE-selectin, sP-selectin, sVCAM-1, sICAM and homocysteine (p>0.05), where as the hs-CRP value was significantly higher in patients with isolated hypertriglyceridemia compared to the control group (p=0.001)., Conclusion: The increase of adhesion molecules, homocysteine and hs-CRP in polygenic hypercholesterolemia subjects compared to the isolated hypertriglyceridemia group reflects their high cardiovascular risk.

Background: To determine the ocular changes related to hypothyrodism in newly diagnosed patients without orbitopathy., Findings: Thirty-three patients diagnosed to have primary overt hypothyroidism were enrolled in the study. All subjects were assigned to underwent central corneal thickness (CCT), anterior chamber volume, depth and angle measurements with the Scheimpflug camera (Pentacam, Oculus) and cup to disc ratio (C/D), mean retinal thickness and mean retinal nerve fiber layer (RNFL) thickness measurements with optical coherence tomography (OCT) in addition to ophthalmological examination preceeding the replacement therapy and at the 1(st), 3(rd )and 6(th )months of treatment. The mean age of the patients included in the study were 40.58 +/- 1.32 years. The thyroid hormone levels return to normal levels in all patients during the follow-up period, however the mean intraocular pressure (IOP) revealed no significant change. The mean CCT was 538.05 +/- 3.85 mu initially and demonstrated no statistically significant change as the anterior chamber volume, depth and angle measurements did. The mean C/D ratio was 0.29 +/- 0.03 and the mean retinal thickness was 255.83 +/- 19.49 mu initially and the treatment did not give rise to any significant change. The mean RNFL thickness was also stable during the control visits, so no statistically significant change was encountered., Conclusions: Neither hypothyroidism, nor its replacement therapy gave rise to any change of IOP, CCT, anterior chamber parameters, RNFL, retinal thickness and C/D ratio.

The main aim of this study is to evaluate the role of blink reflex for early diagnosis of cranial neuropathy in diabetic patients with or without polyneuropathy. Ninety-five diabetic patients were included in the present study for the evaluation of blink reflex. The diabetic patients were divided into two groups according to having diabetic neuropathy or not. Both R1, R2i and R2c latencies in all diabetic patients with or without polyneuropathy were prolonged relative to controls and the differences were statistically significant (p < .001). R1 latencies in diabetic patients with polyneuropathy were prolonged relative to diabetic patients without polyneuropathy and the differences were statistically significant (p < .001). These findings presumably reflect that facial nerve is severly involved in diabetic polyneuropathy. Finally blink reflex is of value in detection of clinically silent intraaxial brainstem functional abnormalities or extraaxial lesions in diabetic patients before peripheral neuropathy.

Background: The aim of the present study was to evaluate left ventricle (LV) systolic and diastolic function, using tissue Doppler echocardiography (TDE) and color M-mode flow propagation velocity, in relation to blood glucose status in normotensive patients with type 2 diabetes mellitus (T2DM) who had no clinical evidence of heart disease., Methods: Seventy-two patients with T2DM (mean age 49.1 +/- 9.8 years) without symptoms, signs or history of heart disease and hypertension, and 50 ages matched healthy controls (mean age 46.1 +/- 9.8 years) had echocardiography. Systolic and diastolic LV functions were detected by using conventional echocardiography, TDE and mitral color M-mode flow propagation velocity (V(E)). Fasting blood glucose level (FBG) after 8 hours since eating a meal, postprandial blood glucose level (PPG), and HbA(1C) level were determined. The association of FBG, PPG and HbA(1C) with the echocardiographic parameters was investigated., Results: It was detected that although systolic functions of two groups were similar, diastolic functions were significantly impaired in diabetics. No relation of FBG and PPG with systolic and diastolic functions was determined. However, HbA(1C) was found to be related to diastolic parameters such as E/A, Em/Am, V(E) and E/V(E) (beta=-0.314, P = < 0.05; beta=-0.230, P < 0.05; beta=-0.602, P < 0.001, beta= 0.387, P < 0.005, respectively). In addition to HbA(1C), LV, diastolic functions were also correlated with age and diabetes duration., Conclusion: Diastolic LV dysfunction may develop even in absence of ischemia, hypertension, and LVH in T2DM. FBG and PPG have no effect on LV functions, but HbA(1C) levels may affect diastolic parameters.

Objective: To determine the frequency of antithyroid antibodies and the presence of autoimmune thyroiditis among patients with primary Sjögren's syndrome., Design: A case-control study., Methods: 53 consecutive patients with primary Sjögren's syndrome, 30 with rheumatoid arthritis, 12 with secondary Sjögren's syndrome associated with rheumatoid arthritis, 17 with autoimmune thyroiditis, and 53 apparently healthy controls were studied for anti-TG and anti-TPO antibodies as well as serum thyroid hormones and TSH levels., Results: The overall frequencies of thyroid antibodies were 6/53 (11%) in primary Sjögren's syndrome, 2/30 (7%) in rheumatoid arthritis, 2/12 (17%) in secondary Sjögren's syndrome, 4/53 (8%) in healthy controls, and 16/17 (94%) in autoimmune thyroiditis. There was no difference in the frequency of the thyroid antibodies among the groups if patients with autoimmune thyroiditis were excluded (p = 0.415 for anti-TPO; p = 0.275 for anti-TG; p = 0.696 for either anti-TG and/or anti-TPO). Only two patients with primary Sjogren's syndrome had clinical hypothyroidism associated with autoimmune thyroiditis., Conclusions: In this Turkish population, no association between primary Sjögren's syndrome and autoimmune thyroiditis was found.