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

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 < 0.001). UTI was detected in 60 patients. ROC analysis showed that a HbA1c of > 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.

Effect of methimazole on warfarin anticoagulation in a case of Graves' disease.

The article describes a case of Graves' disease treated with methimazole and examines the influence of methimazole-induced alterations of thyroid hormone concentrations during warfarin therapy. A 22-year-old woman presented at our endocrinology outpatient clinic with palpitations, sweating, fatigue, tremors, and diarrhea. She had a pain in her right leg and had difficulty walking. Her thyroid profile was consistent with hyperthyroidism. The patient was treated with warfarin 5 mg once a day for deep vein thrombosis for 2 days. Since a therapeutic range of International Normalized Ratio levels could not be achieved, methimazole was stopped due to drug-drug interaction. Lithium was started instead. A euthyroid state was obtained in 2 weeks together with a therapeutic International Normalized Ratio level. Interactions between warfarin and drugs that alter thyroid hormone concentrations have been reported; however, the extent and significance of the interaction between methimazole and warfarin have been inadequately described. Concomitant therapy with warfarin and antithyroid drugs should be managed by frequent monitoring of both thyroid function and the International Normalized Ratio. Lithium is employed only to provide temporary control of thyrotoxicosis in patients who cannot take thionamide and iodide. The administration of lithium alone or in combination with other drugs is shown to be an effective method of controlling hyperthyroidism when conventional antithyroid drugs show adverse effects or become insufficient. When warfarins are used together with antithyroid medications, adequate anticoagulation may not be obtained due to drug-drug interactions. Lithium can be an alternative drug for antithyroid medication in patients on warfarin therapy.

Phaeochromocytoma combined with subclinical Cushing's syndrome and pituitary microadenoma.

OBJECTIVES: Phaeochromocytoma (PHEO) occasionally associates with pathological lesions of the adrenal cortex. The coexistence of PHEO and pre-clinical Cushing's syndrome (PCS) of the same adrenal gland has rarely been reported. We report a case of PHEO and PCS originating from the same adrenal gland and discuss the peculiar diagnostic aspects of this entity. CLINICAL PRESENTATION: A 64 yr old man was hospitalized to evaluate the right adrenal mass which was discovered incidentally by ultrasonography. He had a history of type 2 diabetes mellitus and hyperlipidemia. Blood pressure measurements were all normal during his hospital stay. Laboratory examination showed: urinary catecholamines were markedly increased. HbA1C of 14.3 %, midnight cortisol of 11(microg/dL), cortisol was not suppressed after the overnight 1 mg oral dexamethasone suppression test (DST): 3.42(microg/dL), 24 hr free cortisol in the urine : 213 microg/day (10-100), cortisol levels were suppressed more than 50% with 8 mg of dexamethasone. CT scan of the adrenal glands showed a 6 cm well encapsulated right adrenal mass together with a clearly normal left adrenal gland. MRI investigation of the sella turcica revealed a pituitary microadenoma on the right side of the adenohypophysis He was treated with alpha and subsequent beta blockers after the diagnosis of PHEO and PCS was made. Right adrenalectomy was performed. The pathology showed typical PHEO with adrenocortical hyperplasia. VMA, metanefrin and free cortisol levels were normalized one month after surgery. CONCLUSION: The present report is a rare case of PHEO combined with PCS in the same adrenal gland.

The use of lithium carbonate in the preparation for definitive therapy in hyperthyroid patients.

OBJECTIVE: The aim of this study was to elucidate the effectiveness of lithium carbonate prior to thyroidectomy or radioiodide therapy in patients with thyrotoxicosis. SUBJECTS AND METHODS: Lithium carbonate was used as preoperative preparation or radioiodide therapy in 5 patients with Graves' disease and in 1 patient with toxic multinodular goiter because of side effects of thionamide in 5 patients and ineffectiveness of antithyroid medication in the remaining patient. RESULTS: All 6 patients had a benign course following treatment without thyroid storm. No adverse effects or complications of lithium carbonate were observed. CONCLUSION: This report shows that lithium carbonate can be safely used preoperatively or prior to radioiodide therapy in circumstances where antithyroid medications are contraindicated and are ineffective in obtaining an euthyroid status.

Associations between sex hormone binding globulin and metabolic syndrome parameters in premenopausal obese women.

BACKGROUND AND AIMS: The aim of this study was to determine sex hormone binding globulin (SHBG) concentrations in premenopausal obese women and to evaluate the relationships between sex hormones and features of the metabolic syndrome (MetS). SETTINGS AND DESIGN: Retrospective cross-sectional analysis was carried out on 350 obese patients aged 25 to 69 years referred to the Department of Endocrinology, Pamukkale University in 2002-2003. MATERIALS AND METHODS: 125 premenopausal euthyroid patients were eligible for this study. Subjects were divided into two groups according to the body mass index (BMI): Group I, women with BMI 2 (n = 17) and Group II,, women with BMI > or = 30 kg/m 2 (n = 108). Median SHBG concentration of Group I was 50.1 nmol/L. Group II was divided into two subgroups according to the median SHBG concentration of Group I: subjects with high SHBG levels (SHBG concentration > or = median level of the control group, i.e > or = 50.1 nmol/L) and subjects with low SHBG levels ( RESULTS: No significant difference was found in mean age between the low and high SHBG groups. The low SHBG group was significantly heavier, and with higher waist circumference than the high SHBG group. In the low SHBG group, fasting glucose, postprandial glucose and gamma glutamyl transferase (GGT) and free androgen index (FAI) were significantly higher. Lipid profile, blood pressure, uric acid, insulin and HOMA were found similar between two groups. Linear regression analyses revealed that body mass index and FAI were significant, being independent predictors of SHBG concentrations in premenopausal women. (r = 0.365, r square = 0.134). CONCLUSIONS: It is concluded that low SHBG concentrations may indicate visceral obesity and glucose intolerance in premenopausal women.

The PPAR-gamma activator rosiglitazone fails to lower plasma growth hormone and insulin-like growth factor-1 levels in patients with acromegaly.

BACKGROUND/AIM: Despite combined therapy consisting of surgery, external X-ray, and medical therapy, a significant number of acromegaly patients continue to have uncontrolled growth hormone (GH) secretion and active disease. These patients, particularly those with large or invasive tumors, require additional therapy to decrease their GH levels. Our aim was to investigate whether patients with documented GH-secreting pituitary adenomas leading to acromegaly would respond with attenuation of GH and insulin-like growth factor-1 (IGF-1) levels after treatment with a peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist. METHODS: We conducted prospective analyses in the Endocrinology Clinic of the Pamukkale University. Acromegaly patients who had active disease participated in two admissions: before and after 6 weeks of daily treatment with 8 mg of oral rosiglitazone. Four male and 3 female patients have completed the study. Basal and nadir GH levels during an oral glucose tolerance test were determined, and the IGF-1 and IGF-binding protein-3 levels were also measured both before and 6 weeks after the rosiglitazone treatment. RESULTS: Treatment with rosigitazone did not reduce basal and nadir GH levels during the oral glucose tolerance test and the IGF-1 levels in the patient population as a whole (p > 0.05). CONCLUSIONS: The PPAR-gamma activator rosiglitazone, used at maximum approved dosage, did not reduce plasma GH and IGF-1 levels in patients with acromegaly. Further studies with higher doses and longer duration of PPAR-gamma agonist administration would be required to determine its usefulness in the treatment in this group of patients.

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 (fT4), 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 (microIU/ml) levels of the two groups were similar (p > 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 fT3 and 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.

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-b 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.

Relationship between insulin and sex hormone-binding globulin levels during weight loss in obese women.

OBJECTIVE: The aim of this study was to assess the impact of insulin sensitivity on the relationship between sex hormone-binding globulin (SHBG) and insulin levels during active weight loss in euthyroid obese women. RESEARCH DESIGN AND METHODS: The study population comprised 80 premenopausal overweight and obese (BMI > or =27) women (mean age 41.44 +/- 10.03 years). Seventy patients were considered eligible for the study. Hypocaloric diets were given to all patients. Of 70 subjects who were initially willing to participate in the study, only 64 continued through to the last stage of the study. MEASUREMENTS: Anthropometric parameters, metabolic markers and sex hormone status were measured at baseline and on completion of the 12-week study period. RESULTS: Following the diet, significant decreases in insulin, homeostasis model assessment (HOMA) for insulin resistance and fasting glucose were noted. However, HOMA insulin secretion values did not change significantly. Interestingly, there was no significant correlation between SHBG and insulin levels at baseline. After weight loss, SHBG concentrations were significantly and negatively correlated with insulin levels. Therefore, it was concluded that, in severe insulin resistance, insulin does not inhibit the SHBG level. These findings could be important, but the authors have not found a similar relationship in the literature. CONCLUSION: The findings of this study provide some clues to the relationship between insulin and SHBG in insulin-resistant obese subjects. Insulin sensitivity or loss of fat tissue or leptin seem to be involved in the relationship between SHBG and insulin.

Effect of insulin sensitivity on SHBG levels in premenopausal versus postmenopausal obese women.

This study was performed to evaluate the impact of insulin sensitivity on sex hormone-binding globulin (SHBG) and sex steroids in premenopausal and postmenopausal euthyroid obese women. A total of 227 women were eligible for this study. All were euthyroid, obese, and overweight; ages ranged from 25 to 69 years. Women were divided into premenopausal (n=151) and postmenopausal (n=76) groups. SHBG, sex steroids, thyrotropin, fasting and postprandial glucose, lipid profile, uric acid, serum insulin, and blood pressure were measured. No significant difference was found in mean SHBG levels between premenopausal and postmenopausal women. The investigators observed that during transition from premenopause to postmenopause, SHBG levels increased in insulin-sensitive women in the postmenopausal group; however, SHBG levels decreased in insulinresistant women. It was concluded that SHBG blood concentration factors are likely to change during transition from premenopause to postmenopause. The positive effect of estradiol on SHBG levels is probably stronger in premenopausal women than in postmenopausal women. It has been noted that after menopause, the impact of insulin resistance on SHBG level seems more important than the effect of estradiol.

High prevalence of thyroid dysfunction and autoimmune thyroiditis in adolescents after elimination of iodine deficiency in the Eastern Black Sea Region of Turkey.

In the present study we evaluated the effects of iodine intake on the prevalence of thyroid dysfunction, autoimmunity, and goiter in two regions with different iodine status after two years of iodization in Turkey. In total 1733 adolescent subjects were enrolled into the study (993 from an iodine-sufficient area--the Eastern Black Sea Region (group 1) and 740 from an iodine-deficient area--Middle Anatolia (group 2)). We measured free thyroxine (FT(4)), thyrotropin (TSH), antithyroid peroxidase antibodies (Anti-TPO), antithyroglobulin antibodies (Anti-Tg), and urinary iodine (UI), and examined the thyroid gland by ultrasound. Median urinary iodine excretion was found to be significantly different in group 1 and group 2 (139 micro/l vs 61micro/l, p < 0.001). Hyperthyroidism was more frequent in group 1 (3.6% vs 0.7%; p < 0.001), but the hypothyroidism rate was similar between groups (1.8% vs 1.4 %; p>0.05). The percentage of anti-Tg positive subjects was found to be 17.6% in group 1 and 6.4% in group 2; that of anti-TPO positive subjects was 4.3% in group 1 and 1.5% in group 2. The prevalence of antithyroid antibody (anti-Tg and/or anti-TPO) positivity was significantly higher in group 1 than in group 2 (18.52% vs 6.62%; p < 0.001). Thyroid volumes of the hyperthyroid subjects in both groups were significantly higher than hypo- and euthyroid subjects. In conclusion, iodine supplementation in Turkey has resulted in the elimination of iodine deficiency in the Eastern Black Sea Region, and this has been accompanied by an increase in the prevalence of autoimmune thyroiditis and thyroid dysfunction.

In vivo and in vitro effects of statins on lymphocytes in patients with Hashimoto's thyroiditis.

BACKGROUND: Statins have apoptotic effects on many cell types. Hashimoto's thyroiditis (HT) is an autoimmune disease in which cell-mediated autoimmune mechanisms are pathogenetically involved. OBJECTIVE: The aim of this study was to evaluate the in vivo effects of Simvastatin on thyroid function, lymphocyte subtypes and also to investigate the apoptotic effects of Simvastatin, Mevastatin, Pravastatin and Cerivastatin on lymphocytes from patients with HT. METHODS: In the first part of the study, 11 patients with HT and subclinical hypothyroidism (SH) were given Simvastatin (20 mg/day) for 8 weeks. Ten patients with SH and HT served as the control group. No treatment was given to controls. Thyroid function, C-reactive protein (CRP) levels and lymphocyte subtypes of both groups were determined before the study and after 8 weeks. In the second part of the study, the apoptotic effects of statins on lymphocytes were evaluated in patients with HT (n = 10) and normal subjects (n = 10) in vitro. Apoptosis was investigated by using Annexin-V and propidium iodide. Lymphocytes from patients and controls were incubated with different concentrations of Simvastatin, Cerivastatin, Mevastatin and Pravastatin. RESULTS: An increase in serum free tri-iodothyronine and free thyroxine levels and a decrease in TSH levels were observed (P < 0.05) with Simvastatin treatment. CD4+ cells and B lymphocytes increased whilst CD8+ cells, natural killer cells and activated T lymphocytes decreased significantly in the treatment group (P < 0.05). The CRP level of the group also decreased with Simvastatin but it did not reach significance (P = 0.057). None of parameters was found to be different from the baseline in the control group. In in vitro experiments, apoptosis was observed in CD3 + (both in CD8+ and CD4+ cells) with all statins in both patient and control samples. Mevalonate, which was used in experiments, reversed apoptosis in some but not all samples. CONCLUSIONS: The results of this study suggested that Simvastatin is an immune modulatory agent and improves thyroid function in patients with HT. This effect is probably mediated via lymphocyte apoptosis as demonstrated with in vitro experiments and is not confined to Simvastatin since Mevastatin, Pravastatin and Cerivastatin also induced apoptosis in lymphocytes.

Thyroid consequences of the Chernobyl nuclear power station accident on the Turkish population.

OBJECTIVE: The Chernobyl accident caused widespread effects across Europe and huge areas were radiocontaminated. The major impact of the accident on human health was a sharp increase in childhood thyroid carcinoma and autoimmune thyroid diseases in exposed populations. The thyroidal effects of the Chernobyl accident have been investigated in most European countries, except Turkey. The aim of the current study was therefore to determine the thyroidal consequences of the Chernobyl nuclear power station accident in a selected Turkish population. DESIGN: This study was designed as a sectional, area study, between October 2000 and March 2001, in two different regions of Turkey. According to the data of the Turkish Atomic Energy Authority, the eastern part of the Black Sea region was the most radiocontaminated area in Turkey at the time of Chernobyl accident, while Middle Anatolia was not seriously affected. Thus, Rize city, which is located in the eastern Black Sea region, served as a study area, and 970 adolescents, living in this region, comprised our study group (group R). On the other hand, Beypazari, which is located in Middle Anatolia, was chosen as the control region, and 710 adolescents living in this location were enrolled into the study as controls (group B). METHODS: During the study, thyroid ultrasounds were performed in all subjects and thyroid volumes were calculated. World Health Organization and International Council for Control of Iodine Deficiency Disorders criteria were used for the determination of goiter. Thyroid fine-needle aspiration biopsy with ultrasound guidance was performed when a nodule was detected. Blood samples for thyroid function tests and thyroid autoantibodies, and urine samples for urinary iodine excretion were collected from all subjects. RESULTS: Thyroid function tests were similar in both groups, but thyroid volumes were found to be higher in group B (13.93+/-5.04 vs 17.66+/-5.58 ml; P<0.001). The prevalence of goiter was found to be 28.25% in group R and 61.95% in group B (P<0.001). Thyroid nodules were determined in 6.28% of subjects in group R and 4.22% of subjects in group B (P=0.065). No malignant lesions were found in either of the regions. Although the percentage of autoantibody-positive subjects did not differ between groups (21.25% in group R vs 18.72% in group B), the mean anti-thyroglobulin level was found to be higher in group R (63.25+/-378.60 vs 51.97+/-333.32 IU/ml; P<0.001) and the mean anti-thyroid peroxidase level was higher in group B (24.14+/-219.09 vs 48.82+/-568.50 IU/ml; P<0.001). The iodine status of the selected regions was found to be significantly different (median urinary iodine excretion was 131 microg/l in Rize and 54 microg/l in Beypazari). CONCLUSIONS: Although there was a slight increase in nodule prevalence and thyroid antibody-positive subjects in the study group, it is hard to conclude that Turkey was affected by the Chernobyl accident. These results, at least the significant differences with regard to the prevalence of goiters between groups, may reflect the different iodine status of the selected regions.

Prevalence and risk factors for methicillin-resistant Staphylococcus aureus colonization in a diabetic outpatient population: a prospective cohort study.

BACKGROUND: Diabetes mellitus is a risk factor for methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection. We attempted to determine the prevalence and risk factors for MRSA colonization in a population of outpatients with diabetes. METHODS: This prospective cohort study enrolled patients with diabetes. Anterior nares cultures were obtained from patients with diabetes admitted to outpatient endocrinology and metabolism clinics, and risk factors for MRSA colonization were analyzed. RESULTS: Out of the 304 patients evaluated, 127 (41.9%) were colonized with S aureus and 30 (9.9%) were colonized with MRSA. Overall, 23.6% of all S aureus isolates were MRSA. In multivariate analysis, factors independently associated with an increased risk of MRSA colonization included the presence of connective tissue disease (odds ratio, 7.075; 95% confidence interval, 2.157-23.209; P = .001) and insulin therapy (odds ratio, 3.910; 95% confidence interval, 1.652-9.251; P = .002). CONCLUSIONS: The prevalence of MRSA colonization in our sample of diabetic outpatients was 9.9%. Independent risk factors for MRSA colonization were the presence of connective tissue disease and insulin use. A better understanding of the epidemiology and risk factors for nasal MRSA colonization in the persons with diabetes may have significant implications for the treatment and prevention of MRSA infections.

Angiotensin-converting enzyme gene polymorphism in overweight and obese Turkish patients with insulin resistance.

The aim of this study was to analyze the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in obese Turkish patients with insulin resistance (IR). Sixty-two obese Turkish patients with IR were enrolled in this study. One hundred healthy people without IR were recruited as the control group. ACE amplification was performed by polymerase chain reaction. The frequency of the DD genotype was significantly higher in obese patients with IR than in control subjects. Of sixty-two patients, 1 (1.6%) had an II genotype, 22 (35.5%) had an ID genotype, and 39 (62.9%) had a DD genotype. The frequency of the I allele in the patient group was significantly lower than in controls. We found that the frequency of the DD genotype was higher in obese Turkish patients with IR. ACE gene I/D polymorphism may be associated with obesity in the Turkish population.

SHBG levels correlate with insulin resistance in postmenopausal women.

BACKGROUND: Overweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance and has been identified as a target for new therapeutic strategies, including early change in lifestyle. Early biochemical markers for identifying at-risk patients will be useful for prevention studies. The aim of this study is to investigate whether or not SHBG level is a useful index of hyperinsulinemia and/or insulin resistance in pre- and postmenopausal obese women. At the same time, the relationship between SHBG concentrations and features of the metabolic syndrome were evaluated. METHODS: 229 women were eligible for this study. MetS was defined by using a modification of the ATP III guidelines. All patients were euthyroid, obese and overweight, 25 to 69 years of age. Subjects were divided into groups of premenopausal women (n=125) and postmenopausal women (n=104). Various fatness and fat distribution parameters, SHBG, sex hormones, FSH, LH, thyroid hormones, serum levels of fasting and postprandial glucose, lipid profile, uric acid and serum insulin, and blood pressure were measured. RESULTS: No significant difference was found in mean SHBG levels between pre- and postmenopausal obese women in this study (p=0.866). In premenopausal obese women, SHBG correlated negatively with BMI, waist circumference, fasting glucose, uric acid levels and FAI. In postmenopausal obese women, SHBG correlated negatively with fasting glucose, postprandial plasma glucose, fasting insulin, HOMA-IR and FAI and positively with HDL. SHBG had a significant inverse association with MetS parameters only in postmenopausal women, also after adjusting for BMI, age and estradiol. CONCLUSIONS: Obesity may influence the levels of endogenous sex steroid, especially after menopause. SHBG concentrations are correlated with features of the metabolic syndrome, particularly in postmenopausal obese women. These results suggest that SHBG may be an index of insulin resistance in postmenopausal obese women.

Insulin-like growth factor-I gene and insulin-like growth factor binding protein-3 polymorphism in patients with thyroid dysfunction.

BACKGROUND AND AIMS: Thyroid hormones have important roles in normal growth and skeletal muscle development. IGF-I is one of the most important growth factors and is needed for the proliferation and development of thyroid cells. It stimulates fibroblasts, follicular and endothelia cells in thyroid gland. It has been shown that thyroid hormones play an important role in the regulation of IGF-I and IGFBP-3. In this study we proposed that IGF-I (CA)(19) and IGFBP-3-202 A/C gene polymorphism may affect thyroid functions. For this purpose, frequency of IGF-I (CA)(19) and IGFBP-3-202 A/C gene polymorphism in hypo- and hyperthyroid patients and possible role of these polymorphism in thyroid functions were investigated. METHODS: This study was performed on 37 volunteer hyperthyroid and 76 hypothyroid patients as well as with 50 healthy subjects as controls. DNA isolation was applied in peripheral blood samples obtained from patients and controls. Required areas were amplified with PCR by using proper primers belonging to these gene areas from the isolated DNA samples. The products were evaluated with visualization by UV gel documentation system. RESULTS: Frequency of IGF-I (CA)(19) gene polymorphism among hypothyroidism patients, hyperthyroidism patients and controls were statistically significant (chi(2) = 11.55, df = 4, p = 0.021). Genotypic variations between hyper- and hypothyroid patients were significant (chi(2) = 11.39, df = 2, p = 0.003), whereas there was no difference in IGF-I (CA)(19) gene polymorphism between the patients and controls. Differences in the IGFBP-3-202 A/C gene polymorphism between controls and hypo- as well as hyperthyroid patients were not significant. But IGFBP-3-202 A/C gene polymorphism genotype frequencies showed a significant difference between hypo- and hyperthyroid patients (chi(2) = 6.24, df = 2, p = 0.044). CONCLUSIONS: These findings suggests that IGF-I (CA)(19) and IGFBP-3-202 A/C gene polymorphisms may be a risk factor for hypothyroidism.

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.

The prevalence of late onset congenital adrenal hyperplasia in hirsute women from Central Anatolia.

Late onset congenital adrenal hyperplasia (LO CAH) can be seen in association with polycystic ovary syndrome (PCOS) or idiopathic hirsutism (IH). The study aimed to find out the prevalence of LO CAH in Central Anatolia among hirsute women. Sixty-three patients with hirsutism were evaluated to determine the frequency of LO CAH by comparing them with their age and body mass index matched 28 healthy controls. Of those 63 hirsute women, 43 were diagnosed as PCOS, and 20 were diagnosed as IH. Following basal hormonal evaluation, all subjects underwent ACTH stimulation test and ACTH stimulated 17-hydroxyprogesterone (17-OH P), 11-desoxycortisol (11-DOC), cortisol (F), and dehydroepiandrosterone sulfate (DHEA-S) levels were determined in all subjects. ACTH stimulated 17-OH P, 11-DOC, and DHEA-S levels did not differ between groups. However, stimulated F levels were found to be higher in hirsute women (p<0.001). Six out of 63 (9.52%) patients with hirsutism met the criterion for 21 hydroxylase deficiency. We found no subject presumed to have 11-beta hydroxylase deficiency, but one subject in control group (3.57%) and two patients among PCOS subjects (4.65%) had exaggerated DHEA-S response which was suggestive of mild 3-beta hydroxysteroid dehydrogenase deficiency. In conclusion, the most frequent form of LO CAH seems to be due to 21 OH deficiency among women with PCOS and IH in Central Anatolia. Mild 3-beta HSD deficiency may also be an underlying cause for hirsutism and it may be seen without any clinical presentation. Adrenal hyperactivity is likely to be the main reason of hyperandrogenemia in women with hirsutism.