Obesity is associated with increased serum TSH level, independent of thyroid function

Objective: To reinvestigate the relationship between circulating TSH levels and adiposity in a cohort of obese people, who have normal thyroid function. Methods: Retrospective cross-sectional analysis was carried out on 226 euthyroid obese or overweight female patients. Thirty-nine female lean and euthyroid subjects (BMI <25 kg/m2) were included in the study group. TSH, free thyroxine (FT4), free triiodothyronine (FT3), fasting plasma levels of insulin and glucose, homeostasis model assessment (HOMA) for insulin resistance (HOMA-IR) and insulin secretion (HOMA-β cell), body weight, height, body mass index (BMI) and waist circumference were assessed. Results: Serum TSH levels were higher in the obese than in the lean subjects. In the study group (lean and obese subjects), there was a significant positive correlation between serum TSH and body weight (r = 0.231, p <0.001), BMI (r = 0.270, p <0.001), waist circumference (r = 0.219, p = 0.001), fasting insulin (r = 0.201, p = 0.002) and HOMA-IR (r = 0.201, p = 0.002); there was no correlation between serum FT4 and any of the parameters. A multivariate linear regression analysis revealed that only BMI (p = 0.012, 95% CI = 0.01-0.08) contributed significantly to the variance of TSH. Conclusions: This study strongly supports existing, but contradictory evidence that serum TSH levels are positively correlated with the degree of obesity and some of its metabolic consequences in overweight people with normal thyroid function

P-glycoprotein polymorphism in hypo- and hyper-thyroidism patients

P-glycoprotein (Pgp) is encoded by the multidrug resistance gene (MDR1) in humans and is the product of MDR1. It is expressed in various tissues and is related to drug distribution in intestinal erythrocytes, capillary endotel of brain, proximal tubules cells of kidneys and liver canalicular cells. Expression of Pgp is affected by Pgp polymorphism, and exon 26 C3435T polymorphism is the most common one. It has been thought that expression of Pgp is high in C-allele subjects and this situation is responsible for the resistance against some drugs and substances. Pgp may have a role in the distribution of thyroid hormones, drugs used for hypo- and hyperthyroidism and the resistance occurred. For this purpose possible relationship between T and C alleles and frequency of Pgp polymorphism as well as thyroid hormone distribution in patients with hypo- and hyperthyroidism was investigated. Thirty five hyperthyroidism patients diagnosed as Graves' disease, 78 hypothyroidism patients diagnosed as Hashimoto's thyroiditis and 100 healthy volunteers were included in the study. According to the results obtained no statistically significant difference was found in Pgp C3435T polymorphism between hypo- and hyperthyroidism patients. In addition, the serum free T3 levels of hyperthyroidism patients with C alleles was higher than those of subjects with T alleles. No statistically significant difference was seen in the CC, CT and TT genotype frequencies between the patients and control groups. In conclusion, it seems that Pgp polymorphism is not a predictor factor for the occurrence of hypo- and hyperthyroidism. There is a significant relationship between Pgp and the elevated serum free T3 levels of hyperthyroidism patients, and further research will help understand this situation. © 2007 Springer Science+Business Media B.V

Effects of substitutive therapy on right ventricular systolic and diastolic functions in patients with idiopathic hypogonadotropic hypogonadism.

There have been controversial studies evaluating ventricular functions in patients with idiopathic hypogonadotropic hypogonadism (IHH). A recent study has demonstrated that low serum testosterone levels are associated with increased cardiovascular mortality. We aimed to investigate ventricular functions by standard echocardiography and examine the effects of substitutive therapy on right ventricular (RV) functions in patients with IHH by means of pulsed wave tissue Doppler imaging (PWTDI). Twenty-three patients with IHH and 31 controls were evaluated by standard echocardiography and PWTDI. Isovolumic acceleration (IVA), myocardial systolic wave (Sm) velocity, myocardial precontraction time (PCTm), and PCTm to contraction time (CTm) ratio were determined as systolic indices. Myocardial relaxation time (RTm), early (Em) velocity, late (Am) velocity, and Em to Am ratio were determined as diastolic indices. Peak pulmonary artery pressure (PAP) was significantly higher in control subjects (p=0.008). IVA and Sm values were similar in patients and controls. Em, Am velocities, and their ratios did not differ. PCTm was significantly longer (p=0.001) and PCTm to CTm ratio was significantly higher in patients (p=0.001). These parameters also decreased after replacement therapy, albeit not statistically significantly (p>0.05). PAP was significantly higher after substitutive therapy (p=0.009). Ventricular functions are normal in patients with IHH. Substitutive therapy has no effects on RV functions. However, substitutive therapy may increase PAP in small amounts, which has no immediate clinical implication with short-term use

Association of SGLT-2 inhibitors with bacterial urinary tract infection in type 2 diabetes

Abstract Objective We aimed to investigate the factors associated with UTI in patients with T2D whether being treated with SGLT-2i or not. Methods Adult patients with T2D, whose urine culture results were available, were analyzed retrospectively. Urine culture was obtained from mid-flow urine. Antibacterial treatment was given to the patients with UTI, which was defined by positive urine cultures and/or clinical findings. We grouped the patients as follows: Group A, those treated with SGLT-2i; and Group B, those not treated with SGLT-2i. Results A total of 101 patients were included. Median age was 56 (45–67), 56.4% (n = 57) of the patients were female. Urine culture was positive in 54.9% (n = 28) and 16% (n = 8) of Group A (n = 51) and Group B (n = 50), respectively. Of those for whom urine culture was positive, Escherichia coli was isolated in 83.3% (n = 30), and both Escherichia coli and Klebsiella pneumoniae (K.pneumoniae) were isolated in 16.7% (n = 6). Klebsiella pneumoniae was isolated only from Group A. The need for and duration of hospitalization were higher in Group A (p  5.8% was associated with UTI with good accuracy (AUC: 0.835, p < 0.001). In multiple logistic regression analysis, SGLT-2i use and glucosuria were positive predictors for UTI (p = 0.004, Odds Ratio: 1984.013; and p = 0.028, and Odds Ratio: 12.480, respectively). Conclusion Besides the association of HbA1c and BMI with UTI, SGLT-2i use and glucosuria predicted UTI. Urine culture is important with respect to the choice of antibacterial treatment, especially in those patients under SGLT-2i treatment. The effect of SGLT-2i on the development of UTI is independent of baseline BMI score or HbA1c

Interaction of plasma homocysteine and thyroid hormone concentrations in the pathogenesis of the slow coronary flow phenomenon

Background and Objective: The slow coronary flow (SCF) phenomenon is an angiographic observation and a well-recognized clinical entity characterized by delayed opacification of vessels in a normal coronary angiogram due to reasons yet unclear. Thyroid hormones exert significant effects on plasma homocysteine (Hcy) levels and microvascular resistance. Recently, several investigators have consistently reported that elevation of the plasma Hcy level can severely disturb vascular endothelial function and play a role in the pathogenesis of SCF. Accordingly, we investigated the levels of plasma Hcy and thyroid hormones and their relationship in patients with SCF. Method: Forty-four patients with angiographically proven SCF (Group I) (mean age 55.5 ± 10.4 years, 26 males) and 44 cases with normal coronary flow (NCF) pattern (Group II) (mean age 53.9 ± 11 years, 22 males) with similar risk profiles were enrolled in the study. Coronary flow patterns of the cases were determined by the thrombolysis in myocardial infarction (TIMI) frame count method. The coronary TIMI frame counts were calculated separately for each coronary artery and their average was determined as the mean TIMI frame count for each subject. Serum levels of free tri-iodothyronine (fT3), free thyroxine (fT 4), thyroid stimulating hormone (TSH) and Hcy were measured. Patients with thyroid disease or on medications with a potential to affect thyroid functions were excluded. Results: There were no statistically significant differences between the groups concerning the demographic characteristics and major cardiovascular risk factors. Mean TIMI frame counts of SCF and NCF groups were 45.9 ± 12 and 23.3 ± 3.7, respectively. fT4 (ng/dl) and TSH (μIU/ml) levels of the two groups were similar (p &gt; 0.05). The level of fT3, the active metabolite of the thyroid hormone family, was dramatically reduced in the SCF group when compared to the NCF group (2.3 ± 0.2 vs. 3.0 ± 0.3, p = 0.0001, respectively). Plasma Hcy levels of patients with SCF were found to be significantly higher than controls (12.2 ± 4.9 vs. 8.5 ± 2.9, p = 0.0001, respectively). Correlation analysis showed a significant negative correlation between the plasma fT 3and Hcy levels and the mean TIMI frame counts (r = -0.31, p = 0.003 vs. r = -0.66, p = 0.0001). Moreover, there was a significant positive correlation between the plasma Hcy levels and the mean TIMI frame counts (r = 0.58, p = 0.0001). Also, fT3 was the only significant determinant of the variance of Hcy in multiple regression analysis (r = -0.30, p = 0.005). Conclusion: fT3 levels were decreased and plasma Hcy levels were increased significantly in patients with SCF as compared to controls. This finding suggests that thyroid hormones and/or (?) a possible disturbance in their metabolism may be responsible for the elevated levels of plasma Hcy in patients with SCF and may play a role in the pathogenesis of the SCF phenomenon. Copyright © 2007 S. Karger AG