Effects of metformin plus rosuvastatin on hyperandrogenism in polycystic ovary syndrome patients with hyperlipidemia and impaired glucose tolerance.

AIM: We aimed to compare the effects of metformin and metformin-rosuvastatin combination therapies on hyperandrogenism in patients with polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: Thirty-eight PCOS patients with hyperlipidemia and impaired glucose tolerance, who were followed at Department of Endocrinology and Metabolism out-patient clinic of Cerrahpasa Medical School were included in the study. Twenty patients had lifestyle changes and metformin (2000 mg/day) therapy (M group) and 18 had statin (rosuvastatin 10 mg/day) in addition to this therapy (MR group). Total and free testosterone, DHEAS, FSH, LH, estrodiol, fasting glucose, insulin, and high-sensitivity C-reactive protein (hs-CRP) levels, lipid parameters and homeostasis model assesment index (HOMAIR) were evaluated for each patient before and 12 weeks after the treatment. RESULTS: After 12 weeks of treatment body mass index (BMI), insulin and glucose levels, HOMA-IR had similar decreaments in both groups, whereas there was a greater decline of the total and free testosterone levels in MR group (p<0.001, p=0.004, respectively). DHEAS levels did not change in M group, however, significantly decreased in MR group after treatment (p=0.8, p=0.002, respectively). As expected hsCRP, triglyceride, total and LDL-cholesterol levels decreased more in MR group. CONCLUSION: Metformin and rosuvastatin combination therapy could lead to a better reduction on hyperandrogenism and on atherosclerosis-related factors in PCOS, in addition to improving lipid parameters.

Plasma viscosity, an early cardiovascular risk factor in women with subclinical hypothyroidism.

OBJECTIVE: It is controversial, if subclinical hypothyroidism increases cardiovascular risk. Plasma viscosity is a hemorheological parameter, which is accepted as an early cardiovascular risk factor. We investigated the alterations in plasma viscosity in women with subclinical hypothyroidism. DESIGN: 40 female patients with subclinical hypothyroidism and 31 age- and weight-matched healthy women were included. Free thyroxine (FT4), thyroid stimulating hormone (TSH), lipid parameters, fibrinogen, C-reactive protein (CRP) levels, hematocrit and plasma viscosity were measured in all subjects. MAIN OUTCOME: Plasma viscosity, total cholesterol and low density lipoprotein were significantly increased and high density lipoprotein was significantly decreased in patients with subclinical hypothyroidism. No significant correlation was found among the parameters. CONCLUSION: Increased plasma viscosity in patients' group suggests that cardiovascular risk might be increased in patients with subclinical hypothyroidism. As far as we could reach, this is the first study concerning plasma viscosity in subclinical hypothyroidism.

Autoimmune thyroiditis and anti-thyroid antibodies in primary Sjogren's syndrome: a case-control study.

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.

Effects of low-dose losartan treatment on persistent microalbuminuria in normotensive type 1 diabetic subjects.

To examine the effect of low-dose losartan, an angiotensin II antagonist, on persistent microalbuminuria in normotensive Type 1 diabetes mellitus, 16 subjects with Type 1 diabetes were randomly assigned to two 2-month treatment periods, with either losartan (25 mg/day) or enalapril (5 mg/day) in a single-blind cross-over design. Urinary albumin excretion (UAE), blood pressures, lipids, glycemia, HbA1C, serum potassium and creatinine clearance were measured before and after each treatment period. The UAEs were similarly reduced after both treatments. The median UAE decreased by 27.8%, from 162 (range 65-250) to 117 (34-190) mg/day (p<0.01) after enalapril, and decreased by 25%, from 160 (60-246) to 120 (36-184) mg/day (p<0.01) after losartan. The systolic and diastolic blood pressures also decreased significantly (p<0.05), whereas serum levels of potassium increased (p<0.01) after both treatments. The levels of serum HbA1c, mean fasting glucose, total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol and creatinine clearances were not significantly (p>0.05 in all) changed by either the enalapril or losartan treatment. No significant differences were found between the effects of enalapril and losartan. In conclusion, losartan treatment reduces microalbuminuria as effectively as enalapril in normotensive Type 1 diabetic patients.

The effect of prolactin and bromocriptine on human peripheral immune status.

The aim of this study was to determine the influence of elevated serum prolactin (PRL) levels on the peripheral lymphocyte subsets in patients with hyperprolactinemia. For this purpose we studied 20 hyperprolactinemic patient lymphocyte subsets by flow cytometry on their hyperprolactinemic state and after their serum prolactin concentration was normalized with bromocriptine (BC) alone or BC and surgery. We observed decreased absolute numbers and percentage of Natural Killer (p=0.0009 and 0.0001, respectively) and CD3/CD25 lymphocytes (p = 0.009 and 0.002) in hyperprolactinemic patients, compared to 8 sex- and age-matched normal controls. There was no correlation between PRL levels and CD16/56 and CD3/CD25 numbers (p=0.72 and 0.33, respectively). We did not find any significant difference in absolute numbers (p = 0.95) and percentage (p = 0.84) of B-lymphocytes of hyperprolactinemic patients, as compared with normal controls. We did not detect any increase in absolute cell numbers of CD16/CD56 (p = 0.21) and CD3/CD25 (p = 0.61) of BC-treated patients when compared to their hyperprolactinemic state. We demonstrated an increase in CD8-cells (p = 0.0173) and a decrease in CD4/CD8 ratio (p = 0.036) in hyperprolactinemic patients treated with BC. There was also an increase in the number of activated T-cells (CD3/HLA DR) in this group, compared to normal controls and the hyperprolactinemic state of the same patients (p = 0.04). In conclusion, elevated PRL levels do not lead to an "overstimulation" of the B-cells, but deteriorate the cytotoxic function.

Impact of initial surgical treatment on survival of patients with differentiated thyroid cancer: experience of an endocrine surgery center in an iodine-deficient region.

This retrospective clinical study was designed to analyze the impact of the initial surgical procedure on the survival of 1000 patients with differentiated thyroid cancer of follicular cell origin who had a thyroid operation and were followed for the 30 years between 1968 and 1998 (median 14 years) in an iodine-deficient region where goiter is endemic. There were 753 women and 247 men with a mean age of 42.8 +/- 6.7 years (range 17-86 years). Patients were divided into three groups. All patients had undergone thyroxine treatment and thyroid-stimulating hormone (TSH) suppression, and most had had iodine-131 treatment postoperatively. Group A consisted of 336 patients with differentiated thyroid cancer (DTC) who were treated with bilateral subtotal thyroidectomy in our institution or elsewhere. Group B consisted of 158 patients with DTC who were treated initially with unilateral total lobectomy and contralateral subtotal lobectomy in our institution or elsewhere and underwent reoperation in our department. Group C consisted of 506 patients with DTC who were treated initially with total or near-total thyroidectomy in our department. Kaplan-Meyer survival analysis was used. Recurrence was seen in 23% and death in 8% of the patients. The 20-year survival rates were 76%, 85%, and 92% for groups A, B, and C, respectively. The survival difference among the patients of group A and groups B and C was found to be statistically different (p < 0.001). Long-term survival of patients with differentiated thyroid cancer living in endemic areas for goiter can be influenced by the initial surgical treatment. Patients treated initially with total or near-total thyroidectomy appear to have a better prognosis.

Helicobacter pylori-induced gastritis may contribute to occurrence of postprandial symptomatic hypoglycemia.

In our clinical experience, postprandial symptomatic hypoglycemic (PSH) patients with H. pylori gastritis showed a substantial improvement in their hypoglycemic symptoms after the eradication of H. pylori. Therefore, in this study we have investigated whether H. pylori gastritis may contribute to the occurrence of PSH. For this purpose, we have evaluated the following parameters in 12 PSH patients with H. pylori gastritis before and one month after the eradication therapy: (1) the number and severity of PSH attacks that occurred in a one-month period using a 30-day diary, (2) the total symptom score following a mixed meal using a visual analog scale questionnaire (VASQ), and (3) the glucose and insulin responses to the mixed meal. After the eradication of H. pylori, the serum insulin responses at 30 and 60 min decreased (P < 0.001 in both), whereas the plasma glucose levels at 150, 180 and 210 min increased significantly (P < 0.001 for 180 min and P < 0.01 in others) following the mixed meal. The number and severity score of PSH attacks that occurred in a one-month period and the area under curve for symptom score in VASQ decreased significantly (P < 0.001 in all). These results suggest that H. pylori gastritis may contribute to the occurrence of PSH.

Glucocorticoid receptors on mononuclear leukocytes in polycystic ovary syndrome.

OBJECTIVE: Many studies have suggested that there is a possible hormonal dysregulation of hypothalamic-pituitary-adrenal (HPA) axis and an increased cortisol clearance in patients with polycystic ovary syndrome (PCOS). Therefore in this study, we have examined the role of glucocorticoid receptor/s (GR) characteristics in the developing of these abnormalities in patients with PCOS. METHOD: For this purpose, the number and affinity of GR in peripheral mononuclear leukocytes (MNL) of 10 patients with PCOS and 10 healthy women (controls) were determined. RESULTS: There were no significant differences in the number (6500+/-1001 sites/cell and 6352+/-1697 sites/cell, respectively; P > 0.05) and affinity (3.93+/-0.89 nM and 4.49+/-0.71 nM, respectively; P > 0.05) of GR between the PCOS patients and the controls. CONCLUSIONS: These results suggest that the alterations in the HPA axis and in the cortisol metabolism observed in PCOS are not related to GR deficiency.

Does Helicobacter pylori-induced gastritis enhance food-stimulated insulin release?

The fact that H. pylori gastritis results in an increased secretion of basal and meal-stimulated gastrin, which is also a physiologic amplifier of insulin release directed us to investigate whether H. pylori gastritis may lead to an enhancement of nutrient-stimulated insulin secretion. For this purpose, we have investigated the insulin responses to both oral glucose and a mixed meal in 15 patients with H. pylori gastritis before and one month after the eradication therapy and also in 15 H. pylori-negative control subjects. The areas under the curve (AUC) for serum insulin following both oral glucose and a mixed meal in the patients with H. pylori gastritis before the eradication were significantly (P < 0.05) higher than those in the H. pylori-negative controls. After the eradication of H. pylori, the AUC for serum insulin following oral glucose and mixed meal decreased by 9.4% and 13.1%, respectively (P < 0.001 in both), and serum basal and meal-stimulated gastrin levels decreased significantly (P < 0.001). These results suggest that H. pylori gastritis enhances glucose and meal-stimulated insulin release probably by increasing gastrin secretion.

Can metformin reduce insulin resistance in polycystic ovary syndrome?

OBJECTIVE: To examine whether metformin is able to reduce insulin resistance in polycystic ovary syndrome (PCOS). DESIGN: Single-blind study comprising two successive periods of treatment: 8 weeks of placebo and 10 weeks of metformin (orally, 850 mg twice daily). SETTING: Clinic of endocrinology and metabolism of Cerrahpasa Medical Faculty at Istanbul University, Istanbul, Turkey. PATIENTS: Sixteen insulin-resistant women with PCOS. INTERVENTIONS: Insulin sensitivity (with an IV insulin tolerance test), plasma glucose and insulin levels during an oral glucose tolerance test (OGTT), serum androgens, and lipids were measured at baseline and after each treatment period. RESULTS: Insulin sensitivity, the mean fasting serum levels of glucose, insulin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total T, free T, androstenedione, DHEAS, and LH:FSH ratio, and the areas under the curve for plasma glucose and insulin during OGTT were not changed by either placebo or metformin treatment. CONCLUSION: Metformin does not decrease insulin resistance in PCOS. This finding suggests that cellular mechanism of insulin resistance in PCOS is different from other common insulin-resistant states such as non-insulin dependent diabetes mellitus and obesity.

The in vitro effects of captopril on the levels of lipid peroxidation and glutathione of erythrocytes in type II diabetes.

Increase in lipid peroxidation (LP) is an indirect marker of free radical activation. The products of LP (malonyldialdehyde: MDA) are increased in diabetic patients, particularly those with angiopathy. Free radicals are eliminated by cellular enzymes such as superoxide dismutase, catalase and glutathione peroxidase. In this study, the effect and the mechanism of action of captopril, and angiotensin converting enzyme (ACE) inhibitor, on lipid peroxidation in erythrocytes from diabetics was investigated. LP and glutathione were studied in 10 type II diabetics (mean age: 57 +/- 10 yr, duration of diabetes: 12 +/- 6 yr) and in 10 healthy subjects (mean age: 30 +/- 5 yr). Lipid peroxidation levels were 20.69 +/- 4.68 MDA% in diabetics and 9.62 +/- 1.87 MDA% in normal subjects. The LP in erythrocytes of type II diabetics was decreased by the increasing concentrations of captopril (before captopril: 20.69 +/- 4.68, after captopril: (2 x 10(-5) M) 16.68 +/- 7.49 MDA%; (4 x 10(-5) M) 14.17 +/- 7.65 MDA%; (6 x 10(-5) M) 12.33 +/- 2.8 MDA%). No difference was found in the inhibition of LP between the captopril concentrations of 6 x 10(-5) M and 10 x 10(-5) M. After preincubation with captopril, the glutathione level did not change significantly in the diabetic and normal erythrocytes. Preincubation with 2-6 x 10(-5) M captopril showed no effect in the normal group (p > 0.05) but 10 x 10(-5) M captopril reduced lipid peroxidation (p < 0.01). In our study, the high levels of lipid peroxidation in erythrocytes from diabetic patients were decreased after preincubation with captopril. Decrease in the level of lipid peroxidation in vitro was independent of the glutathione level. Crosslink binding between MDA and captopril is suggested.