Effects of restoration of the euthyroid state on epicardial adipose tissue and carotid intima media thickness in subclinical hypothyroid patients.

Epicardial adipose tissue (EAT) thickness is a novel cardiovascular risk indicator, whereas carotid intima media thickness (CIMT) is a known marker of subclinical atherosclerosis. The aim of this study was to measure EAT thickness and CIMT in subclinical hypothyroid (SCH) patients and to determine the effect of restoration of the euthyroid state on these variables. The study included 43 patients with SCH (mean age: 35.2±10.7 years; F-M ratio: 42:1) and 30 healthy controls (mean age: 34.5±8.2 years; F-M ratio: 25:5). EAT thickness and CIMT were measured via conventional echocardiography and ultrasonography. Among the patients, 23 were followed up with L-thyroxine replacement until restoration of the euthyroid state and re-evaluated 6 months after baseline. Basal EAT thickness was higher in the SCH patients than in the controls (3.2±0.7 vs. 2.3±0.3 mm-p<0.0001), whereas CIMT was similar in both groups (0.50±0.09 vs. 0.48±0.04 mm). EAT thickness was correlated with CIMT in the patient group (r=0.39, p=0.01), but this correlation was not evident based on multivariate analysis when corrected for age and body mass index (r2=0.47 and p=0.0001 for the model). In the follow-up patient subgroup, both EAT thickness and CIMT decreased significantly following L-thyroxine treatment, when normal TSH levels were attained (3.4±0.7 vs. 2.3±0.5 mm-p=0.007 and 0.51±0.09 vs. 0.46±0.07 mm-p=0.01, respectively). EAT thickness was greater in the SCH patients than in controls, whereas CIMT was similar in both groups. Restoration of the euthyroid state with L-thyroxine treatment was associated with significant decreases in EAT thickness and CIMT in the group of patients that received L-thyroxine treatment and, as such, might reduce the cardiovascular risk associated with SCH.

Amyloid goiter due to familial mediterranean Fever in a patient with byler syndrome: a case report.

BACKGROUND: Familial Mediterranean Fever (FMF), also inherited with autosomal recessive trait, is characterized by recurrent episodes of fever, arthritis, and serositis. Congenital Byler Syndrome (Progressive Familial Intrahepatic Cholestasis) inherited with autosomal recessive trait and characterized by defective secretion of bile acids. FMF associated Amyloid A deposition occurs in many tissues and organs, but amyloid goiter is a rare entity that leads to enlargement and dysfunction of the thyroid. CASE REPORT: We present a rare case of 24 year old male patient who had liver and kidney transplantation due to Byler Syndrome and secondary amyloidosis related to FMF, diagnosed as rapidly growing large amyloid goiter. Deposits of extracellular amyloid and dense adipose metaplasia diagnostic for amyloid goiter are determined upon histopathological examination of thyroidectomy material. CONCLUSION: When goiter was detected in cases with history of systemic amyloidosis and rapidly growing goitre, amyloid goiter should be remembered at first. This case is unique since two autosomal genetic disorders are together in the same patient and important as it emphasizes the consequences of consanguineous marriage, early diagnosis and treatment compliance of FMF and the awareness of amyloid goiter in patients followed by primary care physicians and healthcare professionals.

Vitamin D deficiency is related to thyroid antibodies in autoimmune thyroiditis.

INTRODUCTION: It has been known that vitamin D has some immunomodulatory effects and in autoimmune thyroid diseases, vitamin D deficiency was more prevalent. In this study, our aim was to investigate the relationship between thyroid autoantibodies and vitamin D. MATERIAL AND METHODS: Group 1 and 2 consisted of 254 and 27 newly diagnosed Hashimoto's thyroiditis (HT) and Graves' disease (GD) cases, respectively; age-matched 124 healthy subjects were enrolled as controls (group 3). All subjects (n = 405) were evaluated for 25OHD and thyroid autoantibody [anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-tg)] levels. RESULTS: Group 2 and group 1 patients had lower 25OHD levels than group 3 subjects 14.9 ±8.6 ng/ml, 19.4 ±10.1 ng/ml and 22.5 ±15.4 ng/ml, respectively (p < 0.001). Serum 25OHD levels inversely correlated with anti-tg (r = -0.136, p = 0.025), anti-TPO (r = -0.176, p = 0.003) and parathormone (PTH) (r = -0.240, p < 0.001). Group 2 patients had higher anti-tg and anti-TPO levels than group 1 and 3 (p < 0.001). CONCLUSIONS: In this study, we found that patients with autoimmune thyroid disease (AITD) present with lower vitamin D levels and GD patients have higher prevalence. Since we found an inverse correlation between vitamin D levels and thyroid antibody levels, we may suggest that vitamin D deficiency is one of the potential factors in pathogenesis of autoimmune thyroid disorders.

Vitamin D deficiency is a problem for adult out-patients? A university hospital sample in Istanbul, Turkey.

OBJECTIVE: To investigate the frequency of vitamin D deficiency in relation to demographics, clinical diagnosis, season of measurement and laboratory parameters in adult out-patients. DESIGN: Descriptive, retrospective study concerning evaluation of the initial 25-hydroxyvitamin D (25(OH)D) levels determined at admission in relation to demographics, clinical diagnosis, season of measurement and laboratory parameters. 25(OH)D levels ,20 ng/ml were classified as deficiency, 20­30 ng/ml as insufficiency and .30 ng/ml as sufficiency. SETTING: Out-patient clinics at a tertiary care centre. SUBJECTS: A total of 2488 adult patients (mean age: 53?3 (SD 15?2) years; 85?2% were females) admitted to out-patient clinics at Baskent University Istanbul Hospital were included. RESULTS: Mean level of 25(OH)D in the overall population was 17?4 (SD 11?5) ng/ml while insufficiency and deficiency were evident in 24% and 66% of patients, respectively. Mean 25(OH)D levels in males .45 years old were higher than in their female counterparts (19?4 (SD 11?3) ng/ml v. 17?8 (SD 12?2) ng/ml; P,0?05). Mean 25(OH)D levels obtained in summer (18?6 (SD 11?1) ng/ml) and autumn (23?3 (SD 13?6) ng/ml) were significantly higher than levels in spring (16?1 (SD 10?3) ng/ml) and winter (14?6 (SD 10?2) ng/ml; P,0?01). Mean 25(OH)D levels were determined to be significantly lower in obese patients compared with non-obese patients (15?6 (SD 10?4) ng/ml v. 17?6 (SD 11?6) ng/ml; P,0?05). Levels of 25(OH)D were significantly negatively correlated with serum parathyroid hormone levels (r520?194; P,0?001) while significantly positively correlated with phosphorus (r50?059; P,0?01) and HDL cholesterol (r50?070; P,0?01) levels. CONCLUSIONS: Our findings indicate that vitamin D deficiency is very common among out-patients in Turkey, regardless of gender and age, especially among obese people and during winter and spring.

Association of metabolic syndrome parameters with TT3 and FT3/FT4 ratio in obese Turkish population.

BACKGROUND: Obesity and metabolic syndrome are major health problems worldwide, including Turkey. Recent studies have shown an association between thyroid function tests and metabolic syndrome parameters. In this study, we aimed to determine the frequency of metabolic syndrome in an obese Turkish population and the relationship between metabolic syndrome and thyroid functions. MATERIALS AND METHOD: We recruited 211 patients (187 females/24 males; mean age, 39.7±11.7 years) with body mass index (BMI) >30 kg/m(2) and no other hormonal pathology that could cause obesity. Anthropometric evaluation was followed by measurement of fasting blood glucose (FBG), insulin, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free T3 (FT3), and free T4 (FT4). Metabolic syndrome was defined according to the 2005 revision of the National Cholesterol Education Program Adult Panel III (NCEP ATP III) criteria. Insulin resistance was calculated from homeostasis model assessment of insulin resistance (HOMA-IR) formula. The TSH cutoff value was set at 2.5 mU/L. RESULTS: Metabolic syndrome was diagnosed in 122 patients (58%). Metabolic syndrome positive patients had significantly higher FBG, triglycerides, FT4, systolic (SBP) and diastolic blood pressure (DBP), and statistically lower HDL-C and FT3/FT4 ratio than metabolic syndrome negative patients. TSH decreased with age and was not related with any metabolic syndrome parameters. The FT3/FT4 ratio negatively correlated with FBG, triglycerides, SBP, and DBP (P=0.003, r=-38; P=0.02, r=-0.28; P=0.005, r=-0.35; and P=0.007, r=-0.34, respectively); TT3 positively correlated with HOMA-IR (P=0.006, r=0.40), FBG (P=0.009, r=0.38), and waist circumference (P=0.02, r=0.34). CONCLUSION: Metabolic syndrome frequency was increased in our study population compared to the general population. Metabolic syndrome parameters (except HDL) correlated with TT3, FT4, and the FT3/FT4 ratio. FT4 levels were associated with obesity and metabolic syndrome independently of insulin resistance, whereas TT3 levels were associated with both insulin resistance and metabolic syndrome. This relationship can be explained by compensatory effects of TT3, and probably FT4, on energy expenditure and thermogenesis in obese people.

Bulky gastrinoma of the common bile duct: unusual localization of extrapancreatic gastrinoma--case report.

Zollinger-Ellison syndrome is characterized by elevated levels of serum gastrin associated with increased gastric acid secretion, gastrointestinal ulcerations and diarrhea. Most gastrinomas (75%) occur sporadically and are located within the gastrinoma triangle. Extraduodenal, extrapancreatic and extranodal gastrinomas have been shown in 5.6% of the patients with Zollinger-Ellison syndrome who underwent surgery. We report a 44-year-old female who had been complaining of nausea and diarrhea for 12 years. Abdominal computed tomography and magnetic resonance imaging detected a homogeneous, regular-shaped 6 x 7 cm solid mass, located between the liver, right kidney and inferior vena cava. Somatostatin receptor positive scanning led us to investigate a neuroendocrine tumor. Serum gastrin level was found very high and the patient underwent surgery. Local excision of the tumor was performed, and an 8x6x5 cm, well-capsulated, solitary mass, originating from the common bile duct was removed. The unique feature of our case is the unusual localization, and although the tumor was very large in size, only capsule invasion was observed with no evidence of distant metastasis.

Epicardial adipose tissue thickness in type 1 diabetic patients.

Insulin resistance is getting important in the course of type 1 diabetes mellitus. Visceral fat depot is associated with insulin resistance and assessment of epicardial fat thickness is a way of measuring visceral fat. The aim of the study was to measure epicardial adipose tissue (EAT) thickness and to determine its relationship with waist-hip-ratio (WHR) and estimated glucose disposal rate (eGDR) in adult type 1 diabetic patients. Thirty-six type 1 diabetic patients (aged 31±8 years; Female/Male: 22/14) and 43 age, gender and BMI matched healthy controls were included. Fasting blood glucose (FBG), hemoglobin A1c, and lipid profiles were measured. Waist-hip-ratio (WHR) was calculated. Daily insulin dose/kg of patients were recorded and eGDR of all subjects was calculated. Epicardial adipose tissue (EAT) thickness was evaluated by echocardiography. EAT thickness of the type 1 diabetic patients was significantly higher than controls (3.30±1.06 vs. 2.30±0.34 mm, P<0.0001). EAT thickness was correlated with age (P=0.05; r=0.35), WHR (P=0.003; r=0.67), daily insulin dose/kg (r=0.45, P=0.005), and eGDR (r=-0.55, P=0.0004). Multivariate analysis revealed WHR and eGDR to be related to EAT among age, WHR, daily insulin dose/kg, eGDR, FBG, and hemoglobin A1c (r2 of the model=0.64). Epicardial adipose tissue thickness is increased in type 1 diabetic patients compared to controls and is related to WHR and eGDR in this group of patients. This measurement may point to the presence of insulin resistance in type 1 diabetic patients.

Anti-Saccaromyces Cerevisiae antibodies (ASCA) are elevated in autoimmune thyroid disease ASCA in autoimmune thyroid disease.

Environmental factors have been implicated in the development of autoimmune thyroid disease (AITD). Anti-Saccaromyces Cerevisiae Antibodies (ASCA) were shown to be elevated in several autoimmune diseases. The aim of the study was to determine ASCA levels and their relationship with thyroid autoantibodies in patients with AITD. One-hundred and twelve patients with AITD (age 41.1±12.8 years; F/M:96/16) and 103 healthy controls (38.5±10.3 years; F/M:82/21) were included. Twenty-four patients had Graves disease (GD), and 88 had Hashimoto's thyroiditis (HT). ASCA IgA and IgG, TSH, free T4, anti-thyroglobulin, and anti-thyroid peroxidase antibody concentrations were determined. ASCA IgA positivity in patients with GD (16.6%) was similar to patients with HT (13.6%) and was higher than controls (5.8%). No significant difference was present between the frequencies of IgG positivity among GD (12.5%), HT (7.9%), and control groups (5.8%). The mean levels of ASCA IgA and IgG were comparable within the groups. No correlation of ASCA and anti-thyroglobulin and anti-thyroid peroxidase levels was observed. Increased IgA ASCA positivity is observed in patients with GD, suggesting a role of environmental stimuli in its pathogenesis. The role of ASCA in the etiology of AITD needs to be further examined.

Epicardial fat tissue thickness correlates with endothelial dysfunction and other cardiovascular risk factors in patients with metabolic syndrome.

BACKGROUND: Epicardial adipose tissue has shown to be related to cardiovascular risk. The aim of this study is to investigate the relationship between epicardial adiposity and endothelial function in metabolic syndrome. METHODS: Fifty patients with metabolic syndrome were recruited. Anthropometric measurements, fasting blood glucose, insulin, lipid profile, high-sensitivity C-reactive protein (hsCRP), fibrinogen, apolipoprotein A (Apo A), Apo B1, and lipoprotein (a) [Lp(a)] were determined. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Epicardial fat thickness was measured via two-dimensional M-mode echocardiography. Endothelial function was assessed as flow-mediated dilatation at the brachial artery. RESULTS: Epicardial fat tissue thickness was shown to be correlated negatively with FMD and positively with age, diastolic blood pressure, hsCRP, fibrinogen, HOMA-IR, and lipid parameters. Multiple regression analysis showed epicardial fat tissue thickness to be an independent factor influencing the endothelial function. CONCLUSIONS: Epicardial fat tissue may be a useful parameter in the assessment of patients with metabolic syndrome.

Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects.

CONTEXT: Vitamin D receptors are present in many tissues. Hypovitaminosis D is considered to be a risk factor for atherosclerosis. OBJECTIVE: This study explores the effects of vitamin D replacement on insulin sensitivity, endothelial function, inflammation, oxidative stress, and leptin in vitamin D-deficient subjects. DESIGN, SETTING, AND PATIENTS: Twenty-three asymptomatic vitamin D-deficient subjects with 25-hydroxyvitamin D [25(OH)D] levels below 25 nmol/liter were compared with a control group that had a mean 25(OH)D level of 75 nmol/liter. The vitamin D-deficient group received 300,000 IU im monthly for 3 months. The following parameters were evaluated before and after treatment: vitamin D metabolites, leptin, endothelial function by brachial artery flow mediated dilatation (FMD), insulin sensitivity index based on oral glucose tolerance test, and lipid peroxidation as measures of thiobarbituric acid reactive substances (TBARS). RESULTS: FMD measurements were significantly lower in 25(OH)D-deficient subjects than controls (P = 0.001) and improved after replacement therapy (P = 0.002). Posttreatment values of TBARS were significantly lower than pretreatment levels (P < 0.001). A positive correlation between FMD and 25(OH)D (r = 0.45; P = 0.001) and a negative correlation between FMD and TBARS (r = -0.28; P < 0.05) were observed. There was a significant increase in leptin levels after therapy, and the leptin levels were positively correlated with 25(OH)D levels (r = 0.45; P < 0.05). CONCLUSIONS: This study shows that 25(OH)D deficiency is associated with endothelial dysfunction and increased lipid peroxidation. Replacement of vitamin D has favorable effects on endothelial function. Vitamin D deficiency can be seen as an independent risk factor of atherosclerosis. Hypovitaminosis D-associated endothelial dysfunction may predispose to higher rates of cardiovascular disease in the winter.

Melatonin ameliorates methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in rats.

Nonalcoholic steatohepatitis (NASH) may progress to advanced fibrosis and cirrhosis. Mainly, oxidative stress and excessive hepatocyte apoptosis are implicated in the pathogenesis of progressive NASH. Melatonin is not only a powerful antioxidant but also an anti-inflammatory and anti-apoptotic agent. We aimed to evaluate the effects of melatonin on methionine- and choline-deficient diet (MCDD)-induced NASH in rats. Thirty-two male Wistar rats were divided into four groups. Two groups were fed with MCDD while the other two groups were fed a control diet, pair-fed. One of the MCDD groups and one of the control diet groups were administered melatonin 50 mg/kg/day intraperitoneally, and the controls were given a vehicle. After 1 month the liver tissue oxidative stress markers, proinflammatory cytokines and hepatocyte apoptosis were studied by commercially available kits. For grading and staging histological lesions, Brunt et al.'s system was used. Melatonin decreased oxidative stress, proinflammatory cytokines and hepatocyte apoptosis. The drug ameliorated the grade of NASH. The present study suggests that melatonin functions as a potent antioxidant, anti-inflammatory and antiapoptotic agent in NASH and may be a therapeutic option.

Insulin resistance, adipocyte biology, and thiazolidinediones: a review.

Obesity is a well-recognized risk factor for the development of insulin resistance and the metabolic syndrome. Adipokines secreted from adipocytes play an important role in the pathogenesis of insulin resistance, hypertension, disorders of coagulation, dyslipidemia, and glucose abnormalities associated with insulin resistance or the metabolic syndrome. The selective ligands of the nuclear transcription factor PPARgamma, Thiazolidinediones (TZDs), induce differentiation of preadipocytes to mature and more insulin sensitive adipocytes. This review summarizes adipocyte biology, the role of the adipokines in the pathogenesis of insulin resistance, and the effects of TZDs on insulin resistance and the metabolic disorders associated with it.

Influence of serum folic acid levels on plasma homocysteine concentrations in patients with rheumatoid arthritis.

The purpose of this study was to investigate whether negative effects of methotrexate (mtx) on blood homocysteine (hmc) levels can be prevented with the replacement of folic acid. 42 female patients with rheumatoid arthritis (RA) were studied. Patients were separated into two groups according to their treatment status with mtx (group I: 27 patients taking mtx and folic acid; group II: 15 patients not using mtx). The level of hmc was found to be 6.3+/-2.4 micromol/l in group I and 7.87+/-3.2 micromol/l in group II (p>0.05). Folic acid levels of group I and II were found to be 21.3+/-15.9 ng/ml and 8.41+/-2.86 ng/ml respectively (p<0.001). There was a statistically-significant correlation between age and hmc levels (r=0.386, p=0.012). Negative statistically-significant correlations were observed between folic acid and hmc levels. The effects of mtx on hmc can be prevented with the replacement of folic acid.

In vivo inefficiency of pentoxifylline and interferon-alpha on hepatic fibrosis in biliary-obstructed rats: assessment by tissue collagen content and prolidase activity.

BACKGROUND AND AIM: To evaluate the possible antifibrotic effects of two drugs, pentoxifylline (PTX) and interferon (IFN)-alpha as well as their combination, on a bile-duct-ligated rat hepatic fibrosis model. METHODS: Bile ducts of 34 female Wistar rats were ligated, and 24 bile ducts were sham operated. Bile-duct-ligated rats were divided into four groups, in which either sterile saline, IFN-alpha (100 000 IU/3 days a week), PTX (50 mg/kg/day) or IFN-alpha + PTX were administered. Sham-operated rats were treated at the same doses. On the 28th day, rats were decapitated to obtain blood for the measurements of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT) and bilirubins. Serum prolidase was assayed at the beginning and at the end of the study by the modified Chinard's colorimetric method. Liver prolidase was assayed after tissue homogenization. Liver collagen content was determined by the dye elution method described by Lopez de Leon. Morphometric-densitometric measurements of hepatic fibrosis were quantified by computerized image analysis. RESULTS: The AST, ALT, ALP, GGT and bilirubins, liver prolidase enzyme activity, collagen content and hepatic collagen surface density were found to be increased in bile-duct-ligated rats on day 28. There was no statistically significant recovery or even a change in collagen turnover rate in rats treated with alternate regimens applied in the study (P > 0.05). CONCLUSION: Pentoxifylline, IFN-alpha and their combination have no beneficial effect on experimental fibrosis induced by biliary obstruction.