DO ANDROGENS PREDICT CARDIOVASCULAR RISK INCLUDING CARDIOTROPHIN-1 LEVELS in PATIENTS WITH OBESE and LEAN POLYCYSTIC OVARY SYNDROME.

Introduction: We aimed to investigate Cardiotrophin-1 (CT-1) levels along with other markers of cardiovascular disease and the association of androgen levels with these parameters in both lean and overweight or obese PCOS patients. Material and Methods: The study included 90 overweight or obese PCOS patients with metabolic syndrome (MS) and 80 lean PCOS patients without MS. The control group consisted of 140 healthy females. Anthropometric measurements, plasma glucose, insulin, lipid and hormone profile, homocysteine, hs-CRP, CT-1 levels and carotid-IMT were evaluated in all study subjects. Results: Fasting insulin, HOMA values were significantly higher in obese PCOS patients. Total testosteron levels were higher in both PCOS groups with respect to both controls. Serum homocysteine, hs-CRP, CT-1 and carotid-IMT values were significantly higher in both PCOS groups compared to controls (p=0.001, pCIMT: 0.005). CT-1 was positively correlated with insulin, HOMA, total testosterone, homocysteine, hs-CRP and carotid IMT. After multiple regression analysis, CT-1 was significantly positively correlated with total testosterone, hs-CRP and carotid IMT. Conclusions: CT-1 was associated with other cardiovascular risk markers and its use as a cardiovascular risk marker might be suggested. Cardiovascular risk was increased even in lean PCOS patients without MS and it might be associated with elevated androgen levels.

Is elevated urotensin II level a predictor for increased cardiovascular risk in subjects with acromegaly?

PURPOSE: Acromegaly is a rare disorder existed in the result of overproduction of growth hormone (GH). The disorder is associated with increased cardiovascular risk factors and metabolic abnormalities. Urotensin II (UII), a secreted vasoactive peptide hormone, belonging somatostatin superfamily, plays an essential role in atherosclerosis and glucose metabolism. The aim of this study was to ascertain whether circulating UII levels are altered in subjects with acromegaly, and to describe the relationship between UII and hormonal or cardiometabolic parameters. METHODS: This cross-sectional study included 41 subjects with active acromegaly, 28 subjects with controlled acromegaly, and 37 age- and BMI-matched controls without acromegaly. Hormonal and metabolic features of the subjects as well as carotid intima media thickness (cIMT) and epicardial fat thickness (EFT) were defined. Circulation of UII levels was determined via ELISA. RESULTS: Both active and controlled acromegalic subjects showed a significant elevation of circulating levels of UII with respect to controls. There was no remarkable difference in circulating levels of UII between active and controlled acromegalic groups. Both cIMT and EFT were remarkably increased in acromegaly subjects comparing to controls. UII positively correlated with cIMT, EFT, BMI, and HOMA-IR. There was no correlation between UII and GH, insulin-like growth factor-1. According to the results obtained from regression models, UII levels independently predicted cIMT and EFT. CONCLUSION: Elevated UII levels are associated with severity of cardiovascular risk factors including cIMT and EFT in acromegalic subjects.

Correlation between Bethatrophin and 25(OH)D Concentrations in a Group of Subjects With Normal and Impaired Glucose Metabolism.

Aim: Inducing beta cell replication is a potential therapeutic approach for the treatment of diabetes mellitus. Recently betatrophin was suggested as a novel stimulator of beta cell proliferation in mice but its role in humans remains to be established. We aimed to investigate betatrophin concentration and its association with metabolic parameters in a group of individuals with normal glucose tolerance, pre-diabetes and diabetes mellitus who had not been previously treated. Methods: A total of 72 subjects were recruited for this cross sectional study: 23 subjects with normal glucose tolerance (NGT), 22 subjects with prediabetes, and 27 subjects with diabetes mellitus (DM). Circulating betatrophin concentration, 75 g oral glucose tolerance test, fasting insulin, glycosylated hemoglobin, 25hydroxy vitamin D and HOMA IR were measured. Results: The difference in betatrophin values did not reach statistical significance between the 3 groups [NGT:206 (176-297)pg/mL, Prediabetes:232 (181-254)pg/mL, DM:245 (205-526)pg/mL, p=0.078]. Betatrophin was negatively significantly correlated with BMI and positively significantly correlated with 25(OH)vitD (p=0.043 and p=0.001 respectively). Multivariate linear regression showed that 25(OH) vitD (ß=0.440 p=0.001) and fasting glucose (ß=0.003 p=0.038) were variables associated with betatrophin concentration (R2=0.251). Conclusions: In a group of subjects ranging from those with normal glucose tolerance to newly diagnosed diabetes, we found that 25(OH)D and fasting glucose were factors associated with serum betatrophin concentration.

THE EFFECT OF EXENATIDE THERAPY IN PREVIOUSLY INSULIN-TREATED TYPE 2 DIABETIC PATIENTS.

OBJECTIVE: To evaluate the effect of multiple daily injection (MDI) treatment replaced by Exenatide BID as compared with continuation of MDI. PATIENTS AND METHODS: A total of 140 patients with type 2 diabetes, taking metformin and multiple daily insulin injections, were randomized to exenatide or insulin group that continued their insulin treatment. Patients were followed-up for 16 weeks. Blood glucose profiles, BMI, waist circumference, HbA1C, serum lipids and side effects were assesssed at weeks 0,12 and 16. RESULTS: There were no significant differences between the two groups with respect to baseline parameters. Glycemic control was similar between the two groups. The mean changes in HbA1C in exenatide group were -0.66±0.63% and in insulin group -0.74±0.92 % (p=0.594). In exenatide group, 59.6 % of patients and in insulin group 85.71 % of patients had maintained or improved glycemic control at the end of the study. In insulin group, insulin requirement increased 5.86 ± 4.46 units/day. Body weight and waist circumference decreased significantly in exenatide treatment group with respect to insulin group (p<0.001). CONCLUSIONS: Substituting exenatide for insulin might be an option in insulin-treated, type 2 diabetic patients having obesity, and poor glycemic control. However, patients with longer duration of diabetes and insulin treatment and with lower C-peptide levels might not benefit from exenatide therapy.

MEAN PLATELET VOLUME AND PLATELET FUNCTION ANALYSIS IN ACROMEGALIC PATIENTS BEFORE AND AFTER TREATMENT.

OBJECTIVE: Mean platelet volume (MPV) and platelet function analysis have been studied before in acromegaly, but the effect of treatment on both parameters has not been evaluated. We aimed to investigate MPV and platelet function analysis in acromegalic patients after six-months of treatment. METHODS: Forty patients with active acromegaly and 36 healthy subjects were included in the study. Plasma glucose and lipids, fibrinogen, GH, IGF-1 levels, MPV and platelet function analysis were measured. All patients with acromegaly were re-evaluated six months after treatment. RESULTS: Fasting blood glucose (FBG), GH, IGF-1, fibrinogen levels and MPV values were significantly higher in acromegalic group compared with the control. Platelet function was enhanced significantly (pcol-ADP: 0.002, pcolepinephrine: 0.002). After 6 months of treatment FBG, serum GH, IGF-1, fibrinogen and MPV decreased and collagen/ADP- and collagen/epinephrine-closure times (CT) were increased. Acromegalic patients that were in remission with long-acting SSA after surgery had significantly higher fibrinogen levels and MPV and decreased collagen/epinephrine-CT with respect to the controls (pfibrinogen: 0.001, pMPV: 0.026, pcol-epinephrine: 0.037). CONCLUSION: Acromegaly was associated with increased MPV and enhanced platelet activity. Although growth hormone hypersecretion was controlled by surgery and medical treatment, these parameters did not improve - indicating a still increased risk for cardiovascular events.

IS SUBCLINICAL HYPOTHYROIDISM IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME ASSOCIATED WITH BMI?

OBJECTIVE: To investigate the impact of body weight on the subclinical hypothyroidism observed in patients with PCOS. METHODS: The study included 95 normal weight (Group-1) and 122 overweight or obese women (Group-2) with PCOS. The control group consisted of age and BMI matched healthy individuals and grouped as normal weight (n: 66, Group-3) and overweight or obese (n: 65, Group-4. Women with chronic disease such as overt thyroid dysfunction, late-onset adrenal hyperplasia, and diabetes were excluded from the study. Plasma glucose and lipid profile, thyroid hormones, insulin, FSH, LH, total testosterone, estradiol, progesterone and DHEA-S were measured. RESULTS: While fasting glucose was similar, insulin and HOMA-IR were higher in Group-2 and Group-4 (p: 0.001). The groups were similar with respect to FSH, Estradiol, prolactine, DHEAS. While total testosterone and LH levels were higher (ptestosterone: 0,009), progesterone was lower in both PCOS groups (pprogesterone: 0.041). Free T3, free T4, thyroid antibodies were similar between the groups, but the prevalence of subclinical hypothyroidism was greater in Group-2 and -4 than in Group-1 and -3 (p: 0.044). TSH was only correlated with BMI (r: 0.122, p: 0.02). CONCLUSION: The increased prevalence of subclinical hypothyroidism in women with PCOS might be the result of increased BMI.

Coagulation parameters and platelet function analysis in patients with acromegaly.

OBJECTIVE: Acromegaly is associated with increased cardiovascular morbidity and mortality. The data about the evaluation of coagulation and fibrinolysis in acromegalic patients are very limited and to our knowledge, platelet function analysis has never been investigated. So, we aimed to investigate the levels of protein C, protein S, fibrinogen, antithrombin 3 and platelet function analysis in patients with acromegaly. METHODS: Thirty-nine patients with active acromegaly and 35 healthy subjects were included in the study. Plasma glucose and lipid profile, fibrinogen levels, GH and IGF-1 levels and protein C, protein S and antithrombin III activities were measured in all study subjects. Also, platelet function analysis was evaluated with collagen/ADP and collagen-epinephrine-closure times. RESULTS: Demographic characteristics of the patient and the control were similar. As expected, fasting blood glucose levels and serum GH and IGF-1 levels were significantly higher in the patient group compared with the control group (pglc: 0.002, pGH: 0.006, pIGF-1: 0.001, respectively). But lipid parameters were similar between the two groups. While serum fibrinogen and antithrombin III levels were found to be significantly higher in acromegaly group (p fibrinogen: 0.005 and pantithrombin III: 0.001), protein S and protein C activity values were significantly lower in the patient group (p protein S: 0.001, p protein C: 0.001). Also significantly enhanced platelet function (measured by collagen/ADP- and collagen/epinephrine-closure times) was demonstrated in acromegaly (p col-ADP: 0.002, p col-epinephrine: 0.002). The results did not change, when we excluded six patients with type 2 diabetes in the acromegaly group. There was a negative correlation between serum GH levels and protein S (r: -0.25, p: 0.04)) and protein C (r: -0.26, p: 0.04) values. Likewise, there was a negative correlation between IGF-1 levels and protein C values (r: -0.39, p: 0.002), protein S values (r: -0.39, p: 0.001), collagen/ADP-closure times (r: -0.28, p: 0.02) and collagen/epinephrine-closure times (r:-0.26, p: 0.04). Also, we observed a positive correlation between IGF-1 levels and fibrinogen levels (r: 0.31, p: 0.01). CONCLUSION: Acromegaly was found to be associated with increased tendency to coagulation and enhanced platelet activity. This hypercoagulable state might increase the risk for cardiovascular and cerebrovascular events in acromegaly.

The development of metachronous prostate cancer and chronic myeloid leukemia in a patient with metastatic rectal cancer.

We report herein an unusual case of metachronous triple cancers (rectum, prostate and Philadelphia(+) [Ph(+)] chronic myeloid leukemia [CML]). A metastatic rectal cancer was diagnosed in a 76-year-old male patient, who was treated with transanal tumor resection and chemotherapy. Thirty months from the initial rectal cancer diagnosis, prostate cancer was diagnosed and the patient was administered maximal androgen blockade and received palliative radiotherapy to the lumbar spine because of painful bone metastases. Thirty months after the diagnosis of rectal cancer and 12 months after the diagnosis of prostate cancer the patient developed Ph(+) CML and imatinib treatment was started. After one-year period in remission, CML evolved into accelerated phase and the patient died of intracranial hemorrhage.