The effects of exenatide and insulin glargine treatments on bone turnover markers and bone mineral density in postmenopausal patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) related bone fracture. The effects of glucagon-like peptide-1 receptor analogs for the treatment of T2DM on bone are controversial in human studies. This study aimed to compare the effects of GLP-1 receptor analogs exenatide and insulin glargine treatment on bone turnover marker levels and bone mineral density (BMD) in postmenopausal female patients with T2DM. Thirty female patients with T2DM who were naive to insulin and incretin-based treatments, with spontaneous postmenopause, were randomized to exenatide or insulin glargine arms and were followed up for 24 weeks. BMD was evaluated using dual-energy X-ray absorptiometry and bone turnover markers by serum enzyme-linked immunosorbent assay. The body mass index significantly decreased in the exenatide group compared to the glargine group (P < .001). Receptor activator of nuclear factor kappa-B (RANK) and RANK ligand (RANKL) levels were significantly decreased with exenatide treatment (P = .009 and P = .015, respectively). Osteoprotegerin (OPG) level significantly increased with exenatide treatment (P = .02). OPG, RANK, RANKL levels did not change with insulin glargine treatment. No statistically significant difference was found between the pre- and posttreatment BMD, alkaline phosphatase, bone-specific alkaline phosphatase, and type 1 crosslinked N-telopeptide levels in both treatment arms. Despite significant weight loss with exenatide treatment, BMD did not decrease, OPG increased, and the resorption markers of RANK and RANKL decreased, which may reflect early antiresorptive effects of exenatide via the OPG/RANK/RANKL pathway.

Letrozole Decreased Testosterone-Induced Cell Proliferation and Prolactin Secretion also Increased Apoptosis in MMQ and GH3 Rat Prolactinoma Cell Lines.

Aromatase enzyme plays an essential role in estrogen-induced tumorigenesis. It is expressed in the normal pituitary and more significantly in prolactinoma tissues. The aim of this study was to investigate the effects of an aromatase inhibitor, letrozole, on MMQ and GH3 rat prolactinoma cell lines and evaluate the possible mechanism of action. MMQ and GH3 cells were characterized with demonstrating aromatase enzyme and estrogen receptor alpha expression by PCR and immunofluorescence staining. After dose optimization for testosterone (T) and letrozole (L), four groups were established: only the testosteron-treated group (T) to detect cell proliferation; only letrozole-treated group (L) to investigate apoptotic effects; testosterone and letrozole concomitant-treated group to demonstrate inhibition of testosterone induced cell proliferation with letrozole treatment s(T + L) and control group (C) with no treatment. The proliferation rate of cells was determined by WST-1. For the detection of apoptotic and necrotic cells, Annexin V and caspase-3 labeling was used. Prolactin and estrogen levels were measured with ELISA, and the mRNA expression of aromatase and Esr1 was also determined. Testosterone induced the proliferation of MMQ and GH3 cells and further increased prolactin and estradiol levels. Adding letrozole to testosterone resulted in decreased cellular proliferation and even induced apoptosis. Also, letrozole administration significantly decreased prolactin and estradiol levels. However, letrozole alone had no effects on proliferation and apoptosis. Gene expression of aromatase and Esr1 was also significantly decreased by letrozole treatment. This in vitro study demonstrated that treatment of testosterone proliferating cells with letrozole resulted in decreased prolactin levels and cell proliferation and induced apoptosis, and further loss of aromatase and Esr1 mRNA expression were observed. Although this is an in vivo study, the results showed unique and novel findings which may easily be adapted to clinical use for further verification.

Cushing's disease due to a pituitary adenoma as a component of collision tumor: A case report and review of the literature.

BACKGROUND: The coexistence of two morphologically different tumors attached to each other creates a very rare type of tumor called a collision tumor. Collision tumors containing pituitary adenoma-sellar meningioma have only been described in four cases to date; we discuss a fifth case harboring a collision tumor comprising a pituitary corticotroph adenoma and a sellar meningioma in the same anatomic position. CASE PRESENTATION: A 34-year-old Caucasian woman presented with menstrual irregularity, severe weakness of the proximal muscles, and 10-15 kg weight gain within a year. Basal plasma cortisol and adrenocorticotrophic hormone levels were 17.7 mg/dL and 58 pg/mL, respectively. Her diurnal cortisol rhythm was impaired (plasma cortisol at 23:00, 18.2 mg/dL) and after a 48-hour, 2-mg dexamethasone suppression test, plasma cortisol level was 13.6 mg/dL. The results were consistent with a diagnosis of Cushing's syndrome. We then performed a nocturnal 8-mg dexamethasone suppression test and the suppression of cortisol was not greater than 50% (21.4 to 19.3). A pituitary magnetic resonance imaging revealed a tuberculum sellae meningioma arising from within the sellar region. An operation was chosen in order to examine whether the tumor was an adrenocorticotrophic hormone/corticotropin-releasing hormone-secreting lesion or if there were any microadenomas that could be observed during the operation. Via an extended endoscopic endonasal approach the meningioma was resected successfully. Unexpectedly, our patient complained of nausea and vomiting postoperatively. Plasma cortisol was 2.6 mg/dL and orally administered hydrocortisone treatment was initiated immediately. Histopathological examination revealed that the tumor generally consisted of a pituitary corticotroph adenoma infiltrated by meningioma. Our patient maintained hydrocortisone treatment for 11 months. At the latest visit, she had lost 12 kg, and her hypertension, menstrual irregularity, and weakness of the proximal muscles had disappeared. Her mental and physical wellbeing were restored. CONCLUSIONS: To the best of our knowledge, this is the first report of Cushing's disease due to a pituitary corticotroph adenoma adjacent to a meningioma. Even if a high-dose dexamethasone suppression test fails to suppress basal cortisol level, the importance of considering a suprasellar/sellar meningioma a possible component of a collision tumor presenting as adrenocorticotrophic hormone-dependent Cushing's syndrome is highlighted here.

Mapping the Molecular Basis and Markers of Papillary Thyroid Carcinoma Progression and Metastasis Using Global Transcriptome and microRNA Profiling.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC). In a subgroup of patients with PTC, the disease progresses to an invasive stage or in some cases to distant organ metastasis. At present, there is an unmet clinical and diagnostic need for early identification of patients with PTC who are at risk of disease progression or metastasis. In this study, we report several molecular leads and potential biomarker candidates of PTC metastasis for further translational research. The study design was based on comparisons of PTC in three different groups using cross-sectional sampling: Group 1, PTC localized to the thyroid (n = 20); Group 2, PTC with extrathyroidal progression (n = 22); and Group 3, PTC with distant organ metastasis (n = 20). Global transcriptome and microRNAs (miRNA) analyses were conducted using an initial screening set comprising nine formalin-fixed paraffin-embedded PTC samples obtained from three independent patients per study group. The findings were subsequently validated by quantitative real-time polymerase chain reaction (qRT-PCR) using the abovementioned independent patient sample set (n = 62). Comparative analyses of differentially expressed miRNAs showed that miR-193-3p, miR-182-5p, and miR-3607-3p were novel miRNAs associated with PTC metastasis. These potential miRNA biomarkers were associated with TC metastasis and miRNA-target gene associations, which may provide important clinicopathological information on metastasis. Our findings provide new molecular leads for further translational biomarker research, which could facilitate the identification of patients at risk of PTC disease progression or metastasis.

The coexistence of infundibular pituicytoma and Cushing's disease due to pituitary adenoma: A case report.

OBJECTIVES: Pituicytomas are rare, solid, well-circumscribed, low grade (grade I), non-neuroendocrine, and noninfiltrative tumors of the neurohypophysis or infundibulum, which appear in the sellar/suprasellar regions. Herein, we present a case with Cushing's disease (CD) caused by an ACTH-secreting pituitary adenoma in association with an infundibular pituicytoma. Subject and Results. A 37-year-old male patient presented to the hospital with a six-month history of blurry vision. Physical examination demonstrated plethora, excessive sweating, weight gain, moon facies, and acne. Basal serum cortisol and ACTH levels were 16 µg/dl and 32 pg/ml, respectively. The results of screening tests were suggestive of Cushing syndrome. It was also 1.97 µg/dl following 8 mg dexamethasone suppression test which was consistent with CD. Pituitary MR imaging revealed a single lesion measuring 6x6.5 mm on the pituitary stalk. Infundibular mass excision and pituitary exploration by extended endoscopic endonasal approach were applied. On immunohistochemistry, strong diffuse immunolabeling for both S100 and TTF-1 was noted for the cells of infundibular mass, diagnosed as pituicytoma. Because the developed panhypopituitarism postoperatively, patient was discharged with daily desmopressin, levothyroxine, hydrocortisone, and intramuscular testosterone, once a month. CONCLUSIONS: Pituicytoma is an uncommon noninvasive tumor of the sellar and suprasellar regions. In this case report, we described a patient with Cushing's disease to whom MRI displayed only an infundibular well-circumscribed lesion, but not any pituitary adenoma. Despite the absence of any sellar lesion, awareness of other undetected possible lesion and exploring hypophysis during the transsphenoidal surgery is mandatory for the correct diagnosis.

Papillary thyroid carcinoma presenting as a primary renal tumor with multiple pulmonary and bone metastases: a case report.

BACKGROUND: Papillary thyroid carcinoma is the most common endocrine malignancy. Distant metastasis from differentiated thyroid carcinoma is infrequent and the metastasis rate of papillary thyroid carcinoma is lower than that of follicular thyroid carcinoma. Distant metastases from differentiated thyroid carcinoma are usually seen in the lungs and bones; however, renal metastasis is very rare. CASE PRESENTATION: Here we describe an 85-year-old Caucasian woman who presented with right flank pain 10 years ago. We describe a case of papillary thyroid carcinoma presenting as a primary renal tumor with extensive pulmonary and bone metastases. Abdominal screening with computed tomography revealed a mass on her right kidney, which was considered a primary renal cell carcinoma and she underwent a right nephrectomy. Unexpectedly, papillary thyroid carcinoma metastasis was diagnosed from demonstrative histopathological findings, such as positive immunoperoxidase staining for thyroglobulin. A total thyroidectomy was performed. Unenhanced thoracic computed tomography and skeletal scintigraphy revealed bilateral multiple nodules in her lungs and bone metastasis on T10 vertebra and right sacroiliac joint. Initially, 30 Gy radiotherapy was implemented to her T9-10 vertebrae and then she was treated with a total of 800 mCi radioactive iodine for ablation. A radioactive iodine whole body scan was performed after each 200 mCi and continuous progression was shown in each scan. After she was lost to follow-up for 3 years, she referred to our clinic again with a draining mass on her neck and we planned radiotherapy to this giant mass. CONCLUSION: Our patient was surprisingly still alive after metastatic disease was diagnosed 10 years ago and she had no major complaint other than a draining mass on her neck. Our primary aim by sharing this case is to underline potential renal metastasis from papillary thyroid carcinoma. In other words, when approaching primary renal tumors, possible distant metastases of other organs need to be kept in mind for differential diagnosis. In addition, it should be noted that if managed appropriately, the long-term survival in patients with papillary thyroid carcinoma with multiple organ metastases could be encouraging.

The effect of somatostatin analogues on Ki-67 levels in GH-secreting adenomas.

PURPOSE: Somatostatin analogues (SSAs) can slow down the growth of neuroendocrine tumors. However, the mechanism remains unclear. Recent studies on patients with acromegaly suggest that SSAs may induce apoptosis, increase autophagy, and decrease cell proliferation of pituitary adenoma. Ki-67-labeling index is a marker of cellular proliferation; therefore, decreased levels are associated with inhibition of proliferation. The aim of this study was to evaluate and compare the Ki-67-labeling index of GH-secreting pituitary adenoma tissues in patients who had undergone pituitary surgery twice due to residual or recurrent tumors and had received SSA treatment between the two surgeries. METHOD: Thirty acromegaly patients who met the above criteria were identified and evaluated for the demographic, clinical and radiological features retrospectively. Surgical pathology samples of each operation were stained for Ki-67 and evaluated blindly by a staff pathologist specialized in pituitary diseases. RESULTS: Among patients who received SSA treatment between the first and second operations, the Ki-67 index of the adenoma at the second operation was significantly lower than the Ki-67 index at the first operation. There were no differences in clinical and radiological prognostic markers between the groups with decreased and unchanged Ki-67 index. CONCLUSION: We concluded that SSA treatment appears to decrease Ki-67 proliferation index independent of tumor features, SSA type, dose and treatment duration. This result suggests that SSA treatment may decrease cellular proliferation, supporting the previous studies.

The Utility of Preoperative ACTH/Cortisol Ratio for the Diagnosis and Prognosis of Cushing's Disease.

PURPOSE: Cushing's syndrome (CS) is a rare disease having diagnostic difficulties. Many diagnostic tests have been defined but none of these are diagnostic alone. Determination of the cause is another problem which sometimes requires more sophisticated and invasive procedures. Therefore, we aimed to evaluate the utility of pretreatment plasma adrenocorticotropic hormone (ACTH)/cortisol ratios in patients with confirmed endogenous CS for the diagnosis and differential diagnosis of CS. MATERIALS AND METHODS: This retrospective evaluation included 145 patients with the diagnosis of CS, 119 patients with Cushing's disease (CD), and 26 patients with ACTH-independent CS (AICS), in a university hospital. Furthermore, 114 individuals in whom CS diagnosis was excluded with at least one negative screening test were enrolled to the study as control group. The clinical, laboratory, imaging, postsurgical pathologic records and also clinical follow-up data of all patients were evaluated. RESULTS: The median basal ACTH/cortisol ratio of the patients with CD was significantly higher than AICS and controls. A cutoff ACTH/cortisol ratio >2.5 was found to be diagnostic for CD with 82% specificity and 63% sensitivity. Among CD group, patients with recurrent disease had higher preoperative ACTH levels and ACTH/cortisol ratio than patients with sustained remission. Furthermore, these patients had more invasive, atypical, and larger tumors. CONCLUSION: An ACTH/cortisol ratio >2.5 would be beneficial to diagnose CD together with other diagnostic tests. It is a simple test with no additional cost. Higher ratios might be related with larger, invasive, and atypical adenoma and also might be helpful to predict recurrence.

Thyroid autoimmunity: is really associated with papillary thyroid carcinoma?

The incidence of thyroid cancer has been greatly increasing. Several studies aimed to investigate biomarkers for prediction of thyroid cancer. Some of these studies have suggested that thyroid autoantibodies (TAb) could be used as predictors of thyroid cancer risk, but the correlation between TAb and PTC is still a matter of debate. The aim of this study is to evaluate thyroid autoimmunity and TAbs in patients with PTC and benign multinodular goiter (MNG) to investigate if TAbs and autoimmune thyroid disease (ATD) could predict thyroid malignancy. A total of 577 patients with thyroid papillary carcinoma (PTC) and 293 patients with benign MNG disease were enrolled postoperatively. Demographic features, thyroglobulin (TgAb) and thyroid peroxidase antibodies (TPOAb) and histologic outcome of the patients were evaluated. The prevalence of ATD and TgAb or TPOAb measurements was not statistically different in PTC and MNG groups. However, tumors were significantly smaller and tumor capsule invasion was seen less frequently in patients with PTC and ATD than without ATD. Patients without ATD had more advanced stage (TNM stage III/IV) tumors than with ATD. Only one of the 11 patients with distant organ metastasis had ATD. The present study demonstrated that the prevalence of ATD diagnosed even with histology or TAb positivity was not different in patients with PTC and MNG. However, having ATD might be associated with a better prognosis in PTC patients.

Histologic outcome of thyroid nodules with repeated diagnosis of atypia in thyroid fine-needle aspiration biopsy.

AIM: We hypothesized that the estimated risk of malignancy for atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is higher than anticipated in Bethesda system. Therefore, we analyzed the actual malignancy risk of repeated AUS/FLUS diagnosis of thyroid fine-needle aspiration biopsies (FNAB). MATERIALS & METHODS: We reported retrospective analyzes of 112 cases with repeated AUS/FLUS diagnosis among 10,769 thyroid FNABs. The histologic follow-up were evaluated in the study. RESULTS: 112 cases with a repeated diagnosis of AUS/FLUS, histologic follow-up revealed 56 (50%) benign, 46 (41%) malignant and ten (9%) well-differentiated tumors of uncertain malignant potential outcome. CONCLUSION: The malignancy risk of AUS/FLUS category in thyroid FNABs was higher than anticipated in Bethesda system. Therefore, the management strategy of AUS/FLUS should be revised.

Aromatase enzyme expression in acromegaly and its possible relationship with disease prognosis.

The purpose of this study was to evaluate aromatase enzyme expression in growth hormone (GH) secreting adenomas and comparison with prolactinomas, nonfunctional adenomas, and normal pituitary tissues. Also the impact of its expression on clinical and prognostic features was evaluated. 38 acromegaly, 26 prolactinoma, and 31 nonfunctional pituitary adenoma and 11 normal pituitary gland samples from autopsies were included. Aromatase and estrogen receptor-alpha (ERα) were evaluated by Immunohistochemical method; demographic, pre- and postoperative features of the patients were noted. Aromatase was expressed in varying degrees in all cases in study including controls. Aromatase expression in patients with acromegaly was significantly higher than patients with prolactinoma, nonfunctional adenoma, and controls (p = 0.04, p = 0.01 and p < 0.001, respectively). Taken together two functional adenoma groups, prolactinoma and acromegaly, aromatase expression was negatively correlated with ER-alpha (p = 0.02, r = -0.34). Also, Ki-67 immunohistochemical results were negatively correlated with aromatase expression (p = 0.03, r = -0.27) while positively correlated with ER expression (p < 0.01). Consistent with the growing evidence about testosterone effect on pituitary functions, aromatase expression was found to be higher in GH-secreting pituitary adenoma. Aromatase was expressed in all pituitary tissues including autopsy samples; however, it was highest in patients with acromegaly. In patients with acromegaly and prolactinoma, aromatase expression was negatively correlated with Ki-67 score, and also it was higher in patients with complete postoperative remission than without remission. Therefore, aromatase expression may be a good prognostic marker predominantly in acromegaly.

Evaluation of exenatide versus insulin glargine for the impact on endothelial functions and cardiovascular risk markers.

AIMS: To demonstrate the efficacy of exenatide versus insulin glargine on endothelial functions and cardiovascular risk markers. METHODS: Thirty-four insulin and incretin-naive patients with type 2 diabetes mellitus (body mass index 25-45 kg/m(2)) who received metformin for at least two months were randomized to exenatide or insulin glargine treatment arms and followed-up for 26 weeks. Measurements of endothelial functions were done by ultrasonography, cardiovascular risk markers by serum enzyme-linked immunosorbent assay, and total body fat mass by bioimpedance. RESULTS: Levels of high sensitivity-C-reactive protein and endothelin-1 decreased (27.5% and 18.75%, respectively) in the exenatide arm. However, in the insulin glargine arm, fibrinogen, monocyte chemoattractant protein-1, leptin and endothelin-1 levels (13.4, 30.2, 47.5, and 80%, respectively) increased. Post-treatment flow mediated dilatation and endothelium independent vascular responses were significantly higher in both arms (p=0.0001, p=0.0001). Positive correlation was observed between the changes in body weight and endothelium-independent vasodilatation, leptin, plasminogen activator inhibitor type 1 and endothelin-1 in both arms (r=0.376, r=0.507, r=0.490, r=0.362, respectively). CONCLUSIONS: Insulin glargine improved endothelial functions, without leading to positive changes in cardiovascular risk markers. Exenatide treatment of 26 weeks resulted in reduced body weight and improvement in certain cardiovascular risk markers and endothelial functions.

Mixed medullary-papillary carcinoma of the thyroid: report of two cases and review of the literature.

Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are two distinct types of thyroid carcinoma with considerable difference in terms of cellular origin, histopathological appearance, clinical course and prevalence. The histogenetic origin and possible molecular mechanisms responsible for the development of mixed medullary-papillary carcinoma of the thyroid are still unclear. The most widely accepted hypotheses considering co-occurrence of MTC and PTC are stem cell theory, collision effect theory and hostage theory. Herein we describe two rare cases of mixed medullary-papillary thyroid carcinoma with co-occurrence of MTC and PTC which developed with concomitant MEN 2A and different sites of lymph node metastasis in the first patient, while with atypical clinical presentation in the second patient. In conclusion, co-expression of thyroglobulin, synaptophysin and chromogranin by the papillary component of mixed tumor seems to support stem cell theory in our first case, whereas positive staining for calcitonin but not for thyroglobulin in the medullary component of the tumor along with separation of these two tumors from each other by a normal thyroid tissue seem to indicates the likelihood of collision effect theory in our second case.

Exenatide treatment exerts anxiolytic- and antidepressant-like effects and reverses neuropathy in a mouse model of type-2 diabetes.

BACKGROUND: Comorbid neurobehavioral disturbances and type-2 diabetes mellitus (T2DM) warrant immediate research attention. Exenatide, which is a potent and selective agonist for the glucagon-like peptide-1 (GLP-1), is used in the treatment of T2DM. Exenatide displays a multitude of effects in the central nervous system. The aim of this study was to investigate the anxiolytic- and antidepressant-like effects and analgesic effects of exenatide in a type-2 diabetic mouse model. MATERIAL/METHODS: Modified elevated plus-maze test for anxiolytic-like, forced swimming test for depression-like behavior and hotplate test for neuropathy were used as behavioral tasks. Behavioral parameters were investigated in a streptozocin--(100 mg/kg, i.p.) and nicotinamide--(240 mg/kg, i.p.) induced type-2 diabetic mouse model. Exenatide (0.1 µg/kg, s.c., twice daily) was administered for 2 weeks. Vehicle (control), diabetic, and exenatide-treated diabetic mice were tested. RESULTS: Our results confirm that exenatide exerts anxiolytic- and antidepressant-like effects and might be effective in diabetic neuropathy in a diabetic mouse model. CONCLUSIONS: Exenatide may be a good candidate as a treatment option for depression, anxiety, and neuropathy in patients with type-2 diabetes.

Endothelial dysfunction and low grade chronic inflammation in subclinical hypothyroidism due to autoimmune thyroiditis.

The relationship between subclinical hypothyroidism (SH) and cardiovascular disease has been one of the most popular topics recently. There is still some controversy concerning its cardiovascular impact and management protocols. Our study aims to investigate the presence of the well known preceding clinical situations of atherosclerosis like endothelial dysfunction and inflammation in subclinical hypothyroidism. Thirty-seven patients with subclinical hypothyroidism (29 women, 8 men) and 23 healthy volunteers (19 women, 4 men) were recruited for the study. Endothelial dysfunction was measured by examining brachial artery responses to endothelium-dependent (flow mediated dilation, FMD) and endothelium-independent stimuli (sublingual nitroglycerin (NTG)). Serum TNF-alpha, interleukin-6, and hs-CRP were measured. The estimate of insulin resistance by HOMA score was calculated with the formula: fasting serum insulin (µIU/mL) x fasting plasma glucose (µM/L) / 22.5. There were no significant differences in age, body mass index, waist circumference, HOMA scores. There was a statistically significant difference in endothelium-dependent (FMD) and endothelium-independent vascular responses (NTG) between the patients with subclinical hypothyroidism and the normal healthy controls. The groups were well matched for baseline brachial artery diameter. The TSH and LDL, IL-6, TNF-alpha and hs-CRP levels in the patient group were significantly higher than those in control group. A positive correlation was found only between endothelium-dependent vasodilation and TNF-alpha, hs-CRP and IL-6, TSH, total cholesterol, LDL and triglycerides. Endothelium-independent vascular response was not correlated with any of the metabolic or hormonal parameters. Neither of the groups were insulin resistant and there was not any difference either in fasting insulin or in glucose levels. We found endothelial dysfunction in subclinical hypothyroidism group. Endothelium-dependent (FMD) and endothelium-independent vascular responses (NTG) were lower in patient group. Our findings suggest that there is endothelial dysfunction and low grade chronic inflammation in SH due to autoimmune thyroiditis. There are several contributing factors which can cause endothelial dysfunction in SH such as changes in lipid profile, hyperhomocysteinemia. According to our results low grade chronic inflammation may be one of these factors.

Plasma visfatin level in women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study is to compare the serum level of visfatin between patients with polycystic ovary syndrome (PCOS) and control subjects matched for age and body mass index (BMI) and to assess the possible correlations of visfatin to the hormonal and metabolic parameters of the syndrome. MATERIAL AND METHOD: Fifty-five patients with PCOS diagnosis composed of 25 obese, 13 overweight, 17 normal weight subjects and 49 women without concomitant disease matched for age and BMI were included in this study. RESULTS: Serum visfatin levels were similar in normal weight PCOS and control group. Visfatin levels in obese and overweight patients with PCOS were higher than that found in control women with similar BMI, and visfatin had positive linear correlation with BMI, waist circumference and HOMA-IR. Obese women with PCOS had also significantly higher visfatin levels than normal weight women with PCOS. CONCLUSION: Visfatin levels in obese and overweight patients with PCOS were higher than that found in females without concomitant disease with similar BMI, and visfatin had positive linear correlation with BMI, waist circumference and HOMA-IR.

Impact of treatment with metformin on adipokines in patients with polycystic ovary syndrome.

BACKGROUND: Adipose tissue synthesizes various adipokines such as resistin, adiponectin and visfatin, which have an effect on insulin resistance. This study was designed to show the effect of metformin, one of the most important drugs used to reduce insulin resistance in patients with polycystic ovary syndrome (PCOS), on these adipokines. METHODS: The study group consisted of 24 women with PCOS and 25 healthy, age- and weight-matched, normally menstruating women. Hormone and lipid profiles, visfatin, adiponectin and resistin were measured in all cases, before and after metformin treatment. RESULTS: Serum visfatin levels were found to be significantly higher in patients with PCOS, compared to controls. Following metformin treatment, a significant decrease was observed in visfatin levels compared to the baseline. A positive correlation was found between serum visfatin levels and BMI, waist circumference, HOMA, insulin and triglyceride levels. No statistically significant difference was observed in terms of serum adiponectin levels in women with PCOS before and after treatment, or in healthy controls. Serum resistin levels were significantly reduced by metformin treatment. CONCLUSION: These findings suggest that visfatin may be related to the obesity and insulin resistance that is frequently encountered in patients with PCOS. A reduction in serum visfatin and resistin levels was shown with metformin treatment, in patients with PCOS.

Association between Circulating Tumor Necrosis Factor-Alpha, Interleukin-6, and Insulin Resistance in Normal-Weight Women with Polycystic Ovary Syndrome.

BACKGROUND: Insulin resistance is a common finding in both obese and lean women with polycystic ovary syndrome (PCOS). Factors contributing to insulin resistance are still controversial. The purpose of the study was to compare the tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) concentrations in normal weight women with PCOS and a weightmatched healthy control group, and also to evaluate the role of these cytokines in the pathogenesis of insulin resistance. METHODS: Thirty-two women with PCOS and 25 age- and weight-matched healthy controls participated in this study. Patients were evaluated clinically and by pelvic ultrasound. Fasting insulin, glucose, lipid profile, follicle-stimulating hormone (FSH), leutinizing hormone (LH), prolactin, testosterone, sex hormone binding globulin (SHBG), 17-hydroxyprogesterone, IL-6, TNF-alpha concentrations, and insulin sensitiviy indices homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) were measured. RESULTS: TNF-alpha and IL-6 concentrations were significantly higher in women with PCOS than in the control group. Significant correlations were found between TNF-alpha serum concentrations and Body Mass Index (BMI), waist circumference, triglyceride concentrations, fasting insulin, and insulin resisitance indices (p < 0.001). IL-6 concentrations were correlated with fasting glucose and insulin resistance (p < 0.05). CONCLUSIONS: The study demonstrated that TNF-alpha and IL-6 concentrations were elevated in normal weight women with PCOS. The findings may contribute to evidence of insulin resistance in lean women with PCOS.

Effect of rosiglitazone on insulin resistance, C-reactive protein and endothelial function in non-obese young women with polycystic ovary syndrome.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) exhibit elevated levels of serum C-reactive protein (CRP) and impaired endothelium dysfunction which are directly correlated with insulin resistance. Because rosiglitazone improves insulin sensitivity, we tested whether rosiglitazone treatment ameliorates high-sensitivity (hs)CRP levels and endothelial dysfunction in these patients. DESIGN: Thirty-one women with PCOS were recruited (mean age, 24.7+/-3.9 (s.e.) years; mean body mass index (BMI), 25.6+/-3.2 kg/m2). All women were treated with 4 mg rosiglitazone daily for 12 months. METHODS: Serum levels of testosterone, LH, FSH, sex hormone-binding globulin (SHBG), insulin and hsCRP were measured. The BMI, hirsutism scores and insulin sensitivity indices were calculated before and after treatment. Arterial endothelium and smooth muscle function was measured by examining brachial artery responses to endothelium-dependent and endothelium-independent stimuli before and after treatment. RESULTS: After treatment with rosigitazone there were significant decreases in serum testosterone (91.2+/-37.5 vs 56.1+/-21.8 ng/dl; P < 0.01) and fasting insulin concentrations (12.5+/-7.6 vs 8.75+/-4.03 microU/ml; P = 0.015). Insulin resistance indices were significantly improved after rosiglitazone treatment (P < 0.05). There were no significant changes in BMI, waist circumference, serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, FSH and LH levels. Hirsutism score was decreased significantly after treatment (10.8+/-1.8 vs 7.6+/-1.7; P < 0.05). Twenty-four of the women reverted to regular menstrual cycles. Levels of SHBG increased significantly after treatment (28.7+/-8.7 vs 48.4+/-11.2 nmol/l; P < 0.01). Serum hsCRP levels were decreased significantly after rosiglitazone treatment (0.25+/-0.1 vs 0.09+/-0.02 mg/dl; P = 0.006). There was also significant improvement in endothelium-dependent vascular responses after rosiglitazone treatment (9.9+/-3.9 vs 16.4+/-5.1%; P < 0.01). CONCLUSIONS: We conclude that rosiglitazone treatment improves insulin sensitivity in women with PCOS. It also decreases androgen production without significant weight gain. More importantly, it has beneficial effects on endothelial dysfunction and low-grade chronic inflammation in normal weight young women with PCOS.