Impact of HLA polymorphisms on the susceptibility to SARS-CoV-2 infection and related mortality in patients with renal replacement therapy.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection could present in a clinical spectrum of varying severity. Human leukocyte antigen (HLA) is a crucial component of the viral antigen presentation pathway and immune response to the virus. Therefore, we aimed to assess the impact of HLA allele polymorphisms on the susceptibility to SARS-CoV-2 infection and related mortality in Turkish kidney transplant recipients and wait listed patients, along with clinical characteristics of the patients. We analysed data from 401 patients with clinical characteristics according to presence (n = 114, COVID+) or absence of SARS-CoV-2 infection (n = 287, COVID-) who had previously been HLA typed to support transplantation. The incidence of coronavirus disease-19 (COVID-19) was 28 %, and the mortality rate was 19 % in our wait listed/ transplanted patients. Multivariate logistic regression analysis showed that a significant HLA association between HLA- B*49 (OR = 2.57, 95 % CI, 1.13-5.82; p = 0.02) and HLA- DRB1*14 (OR = 2.48, 95 % CI, 1.18-5.20; p = 0.01) with SARS-CoV-2 infection. Besides, in COVID + patients, HLA-C*03 was correlated to mortality (OR = 8.31, 95 % CI, 1.26-54.82; P = 0.03). The new finding from our analysis suggests that HLA polymorphisms could be associated with the occurrence of SARS-CoV-2 infection and COVID-19 mortality in Turkish patients with renal replacement therapy. This study may provide new information for the clinician to identify and manage sub-populations at risk in the setting of the current COVID-19 pandemic.

Central venous sampling and magnetic resonance imaging in the diagnosis of ACTH-dependent Cushing's syndrome.

OBJECTIVES: Central venous sampling (CVS) with corticotropin-releasing hormone (CRH) stimulation is a crucial technique in evaluating adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS). We evaluated central venous sampling (CVS) and magnetic resonance imaging (MRI) findings in predicting the localization and lateralization of pituitary microadenomas. METHODS: We analyzed 29 patients with CS who underwent CVS with CRH stimulation and examined with MRI retrospectively. Catheterization to central sinuses was successfully performed in 26 patients. Three patients with variant anatomy or inability to cannulate were diagnosed with CD after examination of pathology. RESULTS: After CVS, among 26 patients, 23 patients were determined to have CD (88.4%) and 2 (7.7%) patients were diagnosed with ectopic ACTH syndrome. One patient was diagnosed with CD postoperatively. While the sensitivity of the CVS was 95.6%, sensitivity of the preoperative pituitary MRI was lower (69.5%). Also, the negative predictive value ratio was higher in CVS than in MRI (66% versus 22%). Diagnostic accuracy in the lateralization of the tumor was high as in CVS as in MRI (76.4% versus 73.9%). CONCLUSION: Central venous sampling with higher sensitivity in the localization of pituitary microadenoma, also has approximately similar diagnostic accuracy in lateralizing the tumor with MRI.

Assesment of attainment of recommended TSH levels and levothyroxine compliance in differentiated thyroid cancer patients.

OBJECTIVE: Thyroid-stimulating hormone (TSH) suppression treatment can induce signs and symptoms of hyperthyroidism and hypothyroidism due to inappropriate treatment or poor compliance to the treatment. The current study aimed to investigate TSH levels, frequency of being on target TSH, adherence to levothyroxine (LT4) suppression treatment in differentiated thyroid cancer (DTC) patients after surgery in a multicentric setting. DESIGN AND PATIENTS: This multicentric cross-sectional study was conducted at 21 medical centres from 12 cities in Turkey. DTC patients followed at least one year in the same center included in the study. Clinical data, serum TSH, free thyroxine (FT4), thyroglobulin (Tg) and anti-Tg levels were recorded during the most recent visit. Body mass index, systolic and diastolic blood pressures, pulse rate were measured. LT4 doses were recorded and doses per kilogram of bodyweight were calculated. Pill ingestion habits recorded and adherence to the therapy were evaluated using the Morisky Medication Adherence Scale and categorized as good, moderate or poor compliant based on their scores. Risk stratification forpredicting the disease persistance and/or reccurence was assessed using the American Joint Committee on Cancer-7th edition thyroid cancer staging calculator. TSH serum concentrations were classified as severe suppression (TSH < 0.01 mU/L), moderate suppression (TSH: 0.01-0.1 mU/L), mild suppression (TSHL 0.1-0.5 mU/L), euthyroid (TSH: 0.5-4 mU/L) and hypothyroid (TSH > 4 mU/L). TSH levels can also be classified as on being on target, under the target, or beyond over the target, according to the American Thyroid Association recommendations. RESULTS: A group of 1125 patients (F/M: 941/184, 50.7 ± 11.7 years) were included in the study. The mean LT4 daily dosage was 132.4 ± 39.6 mcg/day. TSH levels showed severe suppression in 99 (%8.8) patients, moderate suppression in 277 (%24.6) patients and mild suppression in 315 (%28) patients and euthyroid range in 332 (%29.5) patients and hypothyroid range in 97 (8.6%). TSH levels were in target in 29.2% of the patients 20.4% of the patients were undertreated, 50.4% overtreated. The daily LT4 dose and LT4 dose/kg were significantly higher in the severe suppression group (p < .001, p < .001). According to the Morisky scale, 564 patients (50.1%) were good compliant, 368 patients (32.7%) were moderate compliant, and 193 patients (17.1%) were noncompliant. Patients with poor compliance need a higher dose of LT4 compared to the good compliance group (p < .001). TSH levels of patients with good compliance were 0.67 ± 1.96 mU/L and TSH with poor compliance was 2.74 ± 7.47 mU/L (p < .001). TSH levels were similar in patients on fixed and alternating dosages. CONCLUSION: In 29.2% of the DTC patients, serum TSH levels were at target levels. Remaining of the study group have TSH levels under or over treatment range, exposing the patient to medication side effects. Majorty of the study group 82.8% have good or moderate adherence to LT4 therapy. Reaching TSH targets requires simplified and applicable guidelines and following the guideline recommendations.

Identifying Clinical Characteristics of Hypoparathyroidism in Turkey: HIPOPARATURK-NET Study.

Hypoparathyroidism is an orphan disease with ill-defined epidemiology that is subject to geographic variability. We conducted this study to assess the demographics, etiologic distribution, treatment patterns and complication frequency of patients with chronic hypoparathyroidism in Turkey. This is a retrospective, cross-sectional database study, with collaboration of 30 endocrinology centers located in 20 cities across seven geographical regions of Turkey. A total of 830 adults (mean age 49.6 ± 13.5 years; female 81.2%) with hypoparathyroidism (mean duration 9.7 ± 9.0 years) were included in the final analysis. Hypoparathyroidism was predominantly surgery-induced (n = 686, 82.6%). The insulting surgeries was carried out mostly due to benign causes in postsurgical group (SG) (n = 504, 73.5%) while patients in nonsurgical group (NSG) was most frequently classified as idiopathic (n = 103, 71.5%). The treatment was highly dependent on calcium salts (n = 771, 92.9%), calcitriol (n = 786, 94.7%) and to a lower extent cholecalciferol use (n = 635, 76.5%) while the rate of parathyroid hormone (n = 2, 0.2%) use was low. Serum calcium levels were most frequently kept in the normal range (sCa 8.5-10.5 mg/dL, n = 383, 46.1%) which might be higher than desired for this patient group. NSG had a lower mean plasma PTH concentration (6.42 ± 5.53 vs. 9.09 ± 7.08 ng/l, p < 0.0001), higher daily intake of elementary calcium (2038 ± 1214 vs. 1846 ± 1355 mg/day, p = 0.0193) and calcitriol (0.78 ± 0.39 vs. 0.69 ± 0.38 mcg/day, p = 0.0057), a higher rate of chronic renal disease (9.7% vs. 3.6%, p = 0.0017), epilepsy (6.3% vs. 1.6%, p = 0.0009), intracranial calcifications (11.8% vs. 7.3%, p < 0.0001) and cataracts (22.2% vs. 13.7%, p = 0.0096) compared to SG. In conclusion, postsurgical hypoparathyroidism is the dominant etiology of hypoparathyroidism in Turkey while the nonsurgical patients have a higher disease burden with greater need for medications and increased risk of complications than the postsurgical patients.

MONOCYTE/HDL RATIO IN NON-ALCOHOLIC HEPATIC STEATOSIS.

BACKGROUND: Non-alcoholic hepatic steatosis (NAS) is characterized by excess fat accumulation in hepatocytes, causing portal and lobular inflammation and hepatocyte injury. OBJECTIVE: We aimed to evaluate the alterations in monocyte count to high-density lipoprotein cholesterol ratio (MHR) in patients with grade 2 or 3 fatty liver disease and the association of this marker with liver function tests and insulin resistance. METHODS: In this retrospective analysis; patients diagnosed and followed for the grade 2 or 3 fatty liver disease were included in the patient group and the patients who had undergone abdominal ultrasound for any reason and who were not having any fatty liver disease were included in the control group. RESULTS: Totally 409 cases were included in the study. Among participants, 201 were in the control group, and 208 were in the NAS group (111 were having grade 2 and 97 were having grade 3 steatosis). The monocyte/HDL ratio was significantly higher in the NAS group compared with the healthy controls (P=0.001). There was a significant positive correlation between the monocyte/HDL ratio and age (r=0.109; P=0.028), ALT (r=0.123, P=0.014) and HOMA-IR (r=0.325, P=0.001) values. CONCLUSION: In conclusion, the monocyte to high-density lipoprotein ratio significantly increases in fatty liver disease and correlates with insulin resistance. Since it was suggested as a prognostic marker in atherosclerotic diseases, elevated MHR values in fatty liver disease should be evaluated cautiously.

Relação monócito/HDL em esteatose não hepática / Monocyte/hdl ratio in non-alcoholic hepatic steatosis

ABSTRACT BACKGROUND: Non-alcoholic hepatic steatosis (NAS) is characterized by excess fat accumulation in hepatocytes, causing portal and lobular inflammation and hepatocyte injury. OBJECTIVE: We aimed to evaluate the alterations in monocyte count to high-density lipoprotein cholesterol ratio (MHR) in patients with grade 2 or 3 fatty liver disease and the association of this marker with liver function tests and insulin resistance. METHODS: In this retrospective analysis; patients diagnosed and followed for the grade 2 or 3 fatty liver disease were included in the patient group and the patients who had undergone abdominal ultrasound for any reason and who were not having any fatty liver disease were included in the control group. RESULTS: Totally 409 cases were included in the study. Among participants, 201 were in the control group, and 208 were in the NAS group (111 were having grade 2 and 97 were having grade 3 steatosis). The monocyte/HDL ratio was significantly higher in the NAS group compared with the healthy controls (P=0.001). There was a significant positive correlation between the monocyte/HDL ratio and age (r=0.109; P=0.028), ALT (r=0.123, P=0.014) and HOMA-IR (r=0.325, P=0.001) values. CONCLUSION: In conclusion, the monocyte to high-density lipoprotein ratio significantly increases in fatty liver disease and correlates with insulin resistance. Since it was suggested as a prognostic marker in atherosclerotic diseases, elevated MHR values in fatty liver disease should be evaluated cautiously.

RESUMO CONTEXTO: A esteatose não hepática (ENH) é caracterizada pelo acúmulo de gordura nos hepatócitos, causando inflamação portal e lobular e lesões ao hepatócito. OBJETIVO: Avaliar as alterações na contagem de monócitos em relação à proporção de lipoproteína de colesterol de alta densidade (MHR) em doentes com doença hepática gordurosa de grau 2 ou 3 e a associação deste marcador com testes de função hepática e de resistência à insulina. MÉTODOS: Nesta análise retrospectiva os pacientes diagnosticados e seguidos para a doença hepática gordurosa de grau 2 ou 3, foram incluídos no grupo de doentes e os indivíduos que tinham sido submetidos a ecografia abdominal por qualquer motivo e que não tinham qualquer doença hepática gordurosa foram incluídos no de controle. RESULTADOS: Foram incluídos 409 pacientes no estudo. Entre os participantes, 201 estavam no grupo controle e 208 estavam no grupo ENH (111 caracterizados como grau 2 e 97 com esteatose de grau 3). A relação monócito/HDL foi significativamente maior no grupo ENH em comparação com os controles saudáveis (P=0,001). Verificou-se correlação positiva significativa entre a relação monócitos/HDL e a idade (r=0,109; P=0,028), e valores de ALT (r=0,123; P=0,014) e HOMA-IR (r=0,325; P=0,001). CONCLUSÃO: A razão entre monócitos e a lipoproteína de alta densidade aumenta significativamente na doença hepática gordurosa e correlaciona-se com a resistência à insulina. Uma vez que foi sugerido como um marcador prognóstico em doenças ateroscleróticas, os valores elevados de MHR na doença hepática gordurosa devem ser avaliados com cautela.

Arterial stiffness in hyperthyroid patients is deteriorated due to thyroid hormones

ABSTRACT Objective The aim of this study is to evaluate and compare arterial stiffness, which is an independent risk indicator for cardiovascular diseases (CVDs), between patients with overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism by antithyroid therapy and healthy volunteers with pulse wave analysis (PWA). Subjects and methods A total of 102 volunteers were included in the study (30 in the overt hyperthyroid group, 28 in the subclinical hyperthyroid group and 14 with euthyroidism by antithyroid therapy and 30 healthy). The arterial stiffness measurements of the participants in the study were performed with the Mobil-O-Graph PWA device (I.E.M. GmBH, Stolberg, Germany), which makes cuff based oscillometric measurement from the brachial artery. Results Systolic blood pressure, pulse rate, central systolic blood pressure, cardiac output, heart rate-corrected augmentation index (Aix@75) and pulse wave velocity (PWV) measurements were significantly higher in the hyperthyroid group than in the control group. The heart rate and PWV in the subclinical hyperthyroid group were significantly higher than the control group. In the euthyroid group, systolic blood pressure, central systolic blood pressure, cardiac output, cardiac index and PWV were found significantly higher than the control group. There was also a negative correlation between Aix@75 and thyroid-stimulating hormone (TSH), and a positive correlation between Aix@75 and free thyroid hormones. Conclusion In our study, we observed that the arterial stiffness was adversely affected by an overt or subclinical increase in thyroid hormones and this correlated with thyroid hormone levels. We recommend that PWV measurement, which is a simple method for detecting CVD risk, can be used in these patients.

Arterial stiffness in hyperthyroid patients is deteriorated due to thyroid hormones.

OBJECTIVE: The aim of this study is to evaluate and compare arterial stiffness, which is an independent risk indicator for cardiovascular diseases (CVDs), between patients with overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism by antithyroid therapy and healthy volunteers with pulse wave analysis (PWA). SUBJECTS AND METHODS: A total of 102 volunteers were included in the study (30 in the overt hyperthyroid group, 28 in the subclinical hyperthyroid group and 14 with euthyroidism by antithyroid therapy and 30 healthy). The arterial stiffness measurements of the participants in the study were performed with the Mobil-O-Graph PWA device (I.E.M. GmBH, Stolberg, Germany), which makes cuff based oscillometric measurement from the brachial artery. RESULTS: Systolic blood pressure, pulse rate, central systolic blood pressure, cardiac output, heart rate-corrected augmentation index (Aix@75) and pulse wave velocity (PWV) measurements were significantly higher in the hyperthyroid group than in the control group. The heart rate and PWV in the subclinical hyperthyroid group were significantly higher than the control group. In the euthyroid group, systolic blood pressure, central systolic blood pressure, cardiac output, cardiac index and PWV were found significantly higher than the control group. There was also a negative correlation between Aix@75 and thyroid-stimulating hormone (TSH), and a positive correlation between Aix@75 and free thyroid hormones. CONCLUSION: In our study, we observed that the arterial stiffness was adversely affected by an overt or subclinical increase in thyroid hormones and this correlated with thyroid hormone levels. We recommend that PWV measurement, which is a simple method for detecting CVD risk, can be used in these patients.

Evaluation of Cardiovascular Risk With Arterial Stiffness in Patients with Nonfunctioning Pituitary Adenoma.

OBJECTIVE: Nonfunctioning pituitary adenoma (NFPA) accounts for 30% of all pituitary adenomas, and its incidence has been increasing compared to previous years. Increased risk of cardiovascular effects shown in recent studies is noteworthy in patients with NFPA diagnosis, but the number of studies on the subject is limited. In this study, we aimed to assess possible cardiovascular effects and risk via arterial stiffness measurements in patients diagnosed with NFPA. METHODS: We performed arterial stiffness measurements for 30 patients diagnosed with NFPA and 30 healthy volunteers and compared the results to explore the relationship between arterial stiffness parameters, hormone levels, and adenoma size. RESULTS: Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), central SBP, central DBP, augmentation index corrected for a heart rate of 75 beats per minute (AIx@75), and pulse wave velocity (PWV) values of the patients with NFPA diagnosis were significantly higher than the control group. PWV was found to have a significant and negative correlation with growth hormone and insulin-like growth factor 1 (IGF-1). A significant and positive correlation was found between adenoma median short-axis length and PWV. IGF-1 was found to have a significant and negative correlation with adenoma median long- and short-axis length. In multivariate linear regression analysis, we found that IGF-1 was an independent predictor of PWV. CONCLUSION: Both arterial stiffness parameters such as AIx@75 and PWV and peripheral SBP, DBP, and MBP values were found to be high in NFPA patients with no cardiovascular risk factors. Our findings suggest increased cardiovascular effect and risk in patients with NFPA diagnosis, and therefore, we recommend that patients are monitored closely in this respect. ABBREVIATIONS: ACTH = adrenocorticotropic hormone; AIx@75 = augmentation index corrected for a heart rate of 75 beats per minute; BMI = body mass index; CVD = cardiovascular disease; DBP = diastolic blood pressure; FSH = follicle-stimulating hormone; GH = growth hormone; HT = hypertension; IGF-1 = insulin-like growth factor 1; LH = luteinizing hormone; MBP = mean blood pressure; MRI = magnetic resonance imaging; NFPA = nonfunctioning pituitary adenoma; PP = pulse pressure; PWA = pulse wave analysis; PWV = pulse wave velocity; SBP = systolic blood pressure; TSH = thyroid-stimulating hormone.

Nonfunctioning adrenal incidentaloma affecting central blood pressure and arterial stiffness parameters.

PURPOSE: Recently, cardiovascular risk is thought to be increased in patients with nonfunctioning adrenal incidentaloma (NFAI). There are no sufficient studies in the literature to evaluate this situation in NFAI patients without cardiovascular risk. The objective of this study is to compare peripheral and central blood pressure and arterial stiffness between patients with NFAI and healthy volunteers (of a similar age, gender and body mass index as the NFAI group) who have no traditional cardiovascular risk factors and autonomous cortisol secretion, with pulse wave analysis (PWA). METHODS: In this cross-sectional study, we evaluated 35 NFAI patients who have no traditional cardiovascular risk factors and 35 healthy volunteers. PWA was performed in the participants of similar gender, age and body mass index, with a Mobil-O-Graph PWA/ABPM (I.E.M. GmBH, Stolberg, Germany) device. Radiological and biochemical data were obtained retrospectively in the NFAI group. RESULTS: In our study, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), central SBP, central DBP, peripheral vascular resistance, augmentation pressure (AP), heart rate-corrected augmentation index (Aix@75) and pulse wave velocity (PWV) values were significantly higher in the NFAI group compared to the control group. In addition, peripheral and central blood pressure and arterial stiffness parameters were correlated with age and duration of NFAI diagnosis of more than 1 year. CONCLUSIONS: NFAIs are known as cardiometabolically innocent, but in our study, both peripheral and central blood pressure values and arterial stiffness parameters were negatively affected in patients diagnosed with NFAI who have no traditional cardiovascular risk factors. These patients are at risk of cardiovascular diseases.