Acromegaly is associated with high fibroblast growth factor-21 levels.

PURPOSE: Fibroblast growth factor-21 (FGF-21) is a member of fibroblast growth factor family. Both growth hormone (GH) and FGF-21 take place in the regulation of glucose and lipid metabolism. We aimed to investigate FGF-21 levels in acromegaly which is characterized by excess GH levels and is associated with comorbidities and altered body composition. METHODS: We studied 43 subjects (21 females and 22 males, mean age of 50.0 ± 12.8) with acromegaly. The control group consisted of 40 gender- and age-matched subjects (25 females and 15 males, mean age of 48.8 ± 8.8). Acromegaly patients were classified into two groups; active acromegaly (AA; n = 26) and controlled acromegaly (CA; n = 17). Metabolic, anthropometric and laboratory values of subjects were recorded. FGF-21 level was measured by ELISA assay. RESULTS: Median FGF-21 levels were significantly higher in acromegaly group compared to control group (85.5 vs. 59.0 pg/mL, p = 0.02, respectively). In the multiple regression model, FPG, A1c, HOMA-IR, glucose intolerance, BMI, visceral fat, hs-CRP, presence of hypertension, dyslipidemia and acromegaly were included as independent variables to explain variability of plasma FGF-21 levels in whole study group. The presence of acromegaly was the only determinant of increased FGF-21 levels in the whole study group (ß coefficient = 0.253, p = 0.006). CONCLUSION: FGF-21 levels were increased significantly in acromegaly group. Increased FGF-21 levels were significantly and independently associated with the state of acromegaly. Acromegaly may also be a FGF-21 resistance state independent from insulin resistance, glucose intolerance, obesity, hypertension and dyslipidemia.

Circulating insulin-like peptide 5 levels and its association with metabolic and hormonal parameters in women with polycystic ovary syndrome.

PURPOSE: Insulin-like peptide 5 (INSL5) is a gut peptide hormone that is a member of relaxin/insulin superfamily. Growing evidence implicates the crucial role of the peptide in some metabolisms including food intake, glucose homeostasis and reproductive system. Polycystic ovary syndrome (PCOS) is involved in both reproductive and metabolic issues. The aim of the study was determination of circulating levels of INSL5 alteration in women with PCOS and evaluation of the relationship between INSL5 and hormonal-metabolic parameters as well as carotid intima media thickness (cIMT). METHODS: A total of 164 subjects were recruited in this cross-sectional study (82 women with PCOS and 82 age- and BMI-matched controls). Circulating INSL5 levels were assessed via ELISA method. High-resolution B-mode ultrasound was used to measure cIMT. The hormonal and metabolic parameters of the recruited subjects were determined. RESULTS: Circulating INSL5 levels were significantly elevated in women with PCOS compared to controls (27.63 ± 7.74 vs. 19.90 ± 5.85 ng/ml, P < 0.001). The mean values of INSL5 were significantly higher in overweight subjects compared to lean weight subjects in both groups. The women with PCOS having insulin resistance have increased INSL5 compared to those of PCOS subjects without insulin resistance. INSL5 is associated with insulin resistance, BMI, luteinizing hormone and free androgen index. Multivariate logistic regression analyses revealed that the odds ratio for having PCOS in the highest tertile of INSL5 was higher than in the lowest tertile. CONCLUSIONS: PCOS subjects exhibited an elevation in circulating INSL5 levels along with a link between INSL5 level induction and metabolic-hormonal parameters.

Leptin, insulin and body composition changes during adjuvant taxane based chemotherapy in patients with breast cancer, preliminary study.

BACKGROUND: The objectives of the present study were to compare the effect of adjuvant chemotherapy for breast cancer on serum insulin levels, serum leptin levels, and body composition in early stage breast cancer patients. MATERIALS AND METHODS: 17 breast cancer patients underwent 6 cycles of docetaxel (75 mg), epirubicine (100 mg) and cyclophosphamide (500 mg) (TEC). Anthropometrical and foot-to-foot body fat analyzer BIA, serum glucose, insulin, lipids, HOMA-IR and leptin were compared pre- and post-treatment. RESULTS: There was no statistically significant weight gain after treatment; however, there was an overall trend toward weight gain (69.7 ± 9.8 kg vs 71.03 ± 9.8; P= 0.05). From baseline to the end of the study, percentage of body fat and body fat mass showed an upward trend at the end of chemotherapy (1%; 2 kg P> 0.05). Pre and post-treatment period, leptin was strongly correlated with insulin and HOMA-IR (Spearman's pre-T; r = 0.74; P <0.001, r = 0.66; P = 0.004 post-T; r = 0.549; P =0.022, r = 0.51; P =0.036, respectively). Insulin levels were significantly increased in the post-treatment period (P < 0.05). On correlation analysis, post-T insulin levels were correlated with leptin, weight, fat-mass and fat percentage (Spearman's r = 0.549; P=.022, r = 0.567; P= 0.018, r = 0.498, P= 0.042, r = 0.502; P= 0.040, respectively). DISCUSSION: High insulin and leptin levels, important factors that were previously shown to be related to breast cancer outcome, and insulin resistance may be increased in taxane based chemotherapy regimen. These data may have broad implications for diet and lifestyle strategies for the prevention and treatment of cancers.

Epicardial fat, body mass index, and triglyceride are independent contributors of serum fibroblast growth factor 21 level in obese premenopausal women.

PURPOSE: The hormone fibroblast growth factor 21 (FGF-21) regulates carbohydrate and lipid homeostasis. FGF-21 represents an attractive novel therapy for obesity since administration of FGF-21 has been shown to improve metabolic abnormalities in obese animal models. We investigated FGF-21 and its relationship with epicardial fat thickness (EFT), metabolic parameters, and inflammatory markers in premenopausal obese women compared to controls with similar Systematic Coronary Risk Evaluation (SCORE) project risk profiles. METHODS: Forty-five obese premenopausal women with body mass index (BMI) ≥30 kg/m(2) and 41 control premenopausal women with BMI <25 kg/m(2) with similar SCORE project risk profiles were included in this case-control study. EFT was evaluated by two-dimensional transthoracic echocardiography. Serum FGF-21 was measured with an ELISA kit. RESULTS: FGF-21 and EFT were significantly higher in obese women compared to controls (p < 0.001). Multiple stepwise linear regression analysis showed that EFT, BMI, and triglycerides (TG) independently contributed to FGF-21 (R(2) = 0.757, p < 0.001). However, homeostasis model assessment of insulin resistance (HOMA-IR), visceral ectopic fat, and inflammatory markers were not found as a direct contributor to serum FGF-21 level (p > 0.05). CONCLUSIONS: EFT, BMI, and TG may play an important role in predicting serum FGF-21 level which may be a potential therapeutic target in cardiometabolic disorders in the future.

Oxidative and antioxidative status after anthracyclinebased chemotherapy in breast cancer patients.

PURPOSE: The present study was undertaken to evaluate the effects of adjuvant anthracycline-based chemotherapy on thiobarbituric acid reactive substances (TBARS) and superoxide dismutase (SOD) levels in patients with breast cancer who had undergone surgery. METHODS: Body mass index (BMI), serum lipids (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides), serum TBARS and SOD values were assessed in 30 patients with stage III breast cancer receiving adjuvant anthracycline- based chemotherapy. RESULTS: Anthracycline-based chemotherapy had no effect on BMI, blood pressure and lipid profile. A significant elevation was noted in TBARS (5.5±0.6 vs 5.9±0.9 µmol/L; p=0.038) and a significant reduction to baseline values in SOD levels (226.5±61.0 vs 203.1±48.3 U/mL; p=0.03) in patients following 6 cycles of adjuvant chemotherapy. CONCLUSION: The TBARS levels increased, whereas the SOD levels descreased after anthracycline-based chemotherapy. We suggest that oxidative stress is not always detrimental, as it can be beneficial in cancer treatment.

Taxane-based adjuvant chemotherapy reduces endothelin-1 and symmetric dimethylarginine levels in patients with breast cancer.

PURPOSE: To evaluate the levels of asymmetric dimethylarginine (ADMA), an endothelin and nitric oxide (NO) synthase inhibitor, in patients with node-positive breast cancer who had undergone surgery and in a control group including healthy individuals. The effects of taxane-based chemotherapy on endothelin-1 (ET-1) and ADMA levels in the patient group were also studied. METHODS: Body mass index (BMI), serum lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides), ADMA and ET-1 were studied in 19 healthy individuals and in 19 patients with stage II and III, lymph node-positive breast cancer receiving taxane-based chemotherapy. RESULTS: ET-1 (34.3±12.8 vs. 13.8±4.5 pg/mL; p<0.001) and ADMA (0.87±0.18 vs. 0.68±0.24 µmol/L; p=0.024) levels were significantly higher in the breast cancer group compared to the control group. A significant reduction was noted in ET-1 (34.3±12.8 vs. 27.3±4.3 pg/mL; p=0.021) and ADMA (0.87±0.18 vs. 0.73±0.15 µmol/L; p=0.014) levels in patients following 6 cycles of adjuvant chemotherapy to baseline values. CONCLUSION: The present study demonstrated significantly higher levels of ET-1 and ADMA in the breast cancer group compared to the control group, which were reduced significantly with adjuvant taxane-based chemotherapy. It is apparent that prospective studies are needed to understand the effect of reducing ET-1 and ADMA levels on patient survival. We believe that the present study will provide guidance to relevant future studies.

A prudent algorithm for hyperlipoproteinemia in renal transplant recipients.

BACKGROUND: Hyperlipidemia and particularly low-density lipoprotein cholesterol (LDL-C) have been proposed as independent risk factors predisposing to chronic allograft nephropathy. OBJECTIVE: The primary objective of this prospective randomized study was to evaluate the efficacy of the modified National Cholesterol Education Program (NCEP) Step I Diet to prevent posttransplantation hyperlipidemia. The secondary objective was to assess the impact of fluvastatin on the lipid profile of patients unresponsive to dietary measures. METHODS: The study population consisted of 143 consecutive patients who underwent transplantation between October 1998 and January 2005. Patients who failed to demonstrate total and LDL-C levels below the optimal values of 200 mg/dL and 130 mg/dL respectively, were recruited for fluvastatin treatment. The remaining patients who achieved and maintained the target lipid levels continued on the same dietary regimen. RESULTS: Baseline demographic characteristics were not different among the fluvastatin and modified Step I Diet groups. Mean total cholesterol (231.2 vs 187.3 mg/dL; P < .000), LDL-C (134.5 vs 99.2 mg/dL; P < .000), high-density lipoprotein cholesterol (HDL-C; 62.9 vs 55.7 mg/dL; P = .012), and triglyceride (170.3 vs 138.7 mg/dL; P = .011) levels following the dietary run-in period were significantly different between the patients assigned to fluvastatin treatment and those left on the diet, respectively. Fluvastatin achieved reductions ranging from 12% to 14% in the concentrations of total cholesterol (231.2 +/- 4.29 mg/dL to 202.7 +/- 3.89 mg/dL; P < .000) and LDL-C (134.5 +/- 3.53 mg/dL to 115.6 +/- 3.18 mg/dL; P < .000) among 91% of patients after 1 year of treatment. A substantial decrease in all lipoprotein concentrations occurred in 53 patients in the modified Step I Diet group with significant reductions in total cholesterol (187.3 +/- 4.98 mg/dL to 172.7 +/- 3.8 mg/dL; P < .000) and LDL-C (99.2 +/- 4.0 mg/dL to 96.2 +/- 3.44 mg/dL; P < .000). CONCLUSION: Initiation and education of the Step I Diet should be provided during hospitalization. The 3-month dietary run-in period was deemed sufficient to determine the effect of diet on lipid abnormalities. Reduction of lipoprotein levels by a 40-mg daily fluvastatin dose was sufficient, safe, and tolerable.

Impact of calcineurin inhibitors on bone metabolism in primary kidney transplant patients.

OBJECTIVE: Posttransplant bone disease and bone metabolism markers were investigated in primary kidney transplant recipients receiving calcineurin inhibitor (CNI) based triple immunosuppression. We examined the safety profile and independent potential of CNIs on bone formation and bone resorption. The study also attempted to correct for modifiable and nonmodifiable factors that impact on posttransplantation bone metabolism, such as age, renal function, rejection, steroid dosage, and secondary hyperparathyroidism. MATERIALS AND METHODS: Serum alkaline phosphatase and osteocalcin were used as indices of bone formation and urinary deoxypyridinoline as a marker for bone resorption. Bone mineral density (BMD) data were assessed in all patients. Osteocalcin and deoxypyridinoline data were correlated with BMD scores to predict the clinical utility and sensitivity of these tests. Sixty-six patients among 300 kidney transplant recipients were enrolled as eligible candidates based upon more than 12 months' posttransplantation follow-up excellent graft function (GFR values >60 mL/min), and intact parathormone levels <100 pg/mL. RESULTS: Mean follow-up was 1395.3 +/- 179.3 days and 1488.9 +/- 225.1 days for cyclosporine (CsA) and FK506 groups, respectively. Mean values for alkaline phosphatase and osteocalcin were 108.8 +/- 6.0 versus 98.4 +/- 9.7 U/L and 10.1 +/- 1.2 versus 9.8 +/- 1.5 ng/mL for the CsA and FK506 groups, respectively. Both CsA and FK506 caused mild osteoblastic proliferation and matrix mineralization activity, as reflected by increased osteocalcin and alkaline phosphatase levels in 22.6% and 12.5% of patients, respectively. This bone formation activity was counterbalanced by a three-fold increase in urine deoxypyridinoline levels in both groups. Mean deoxypyridinoline levels were, respectively, 13.8 +/- 4.4 versus 11.3 +/- 2.1 nM/mMCr in the CsA and FK506 groups. Thirty-four (68%) patients in the CsA and 10 (62.5%) in the FK506 groups had elevated deoxypyridinoline levels. A strong correlation existed between deoxypyridinoline levels and BMD scores for the CsA group (P < .0001). Despite the presence of relatively greater elevations in deoxypyridinoline and BMD values among CsA-treated patients, there was no significant difference in terms of bone resorption potential of both groups. No correlation existed between iPTH values (<65 pg/mL or among 65 to 98.2 pg/mL) at any time versus osteocalcin, alkaline phosphatase, deoxypyridinoline, or BMD levels. The symptomatic bone disease and fracture rates were 0% in this series. CONCLUSION: Calcineurin inhibitor-based immunosuppression with low maintenance doses of glucocorticoids induces slight bone formation but relatively potent, clinically relevant bone resorption.

The relation of prostate biopsy results and ratio of free to total PSA in patients with a total PSA between 4-20 ng/mL.

OBJECTIVE: In this study our aim was to investigate the efficacy of free to total PSA ratio in discrimination of benign prostate hyperplasia and prostate cancer. MATERIALS AND METHODS: A total of 194 patients, 52 to 82 years old (mean 66.06 +/- 0.47 years) with PSA levels between 4 to 20 ng/mL were included into this study. Each patient underwent sextant prostate biopsy under transrectal ultrasound guidance. The patients were divided into two groups as PSA 4-10 and 10-20 ng/mL. Patients with benign and malign results were compared with respect to age, total PSA level, free PSA level and free/total (f/t) PSA ratio. RESULTS: Biopsies revealed prostate cancer in 16 of 130 patients (12.3%) with serum PSA 4-10 ng/mL and in 10 of 64 patients (15.6%) with serum PSA 10-20 ng/ml. In both PSA groups free PSA and f/t PSA levels were statistically significant, where total PSA levels were not. In patients with 4-20 ng/mL total PSA levels and a cut off level of < 0.18 for f/t PSA, the sensitivity, specificity and positive predictive value for prostate cancer were 88.5%, 53.6% and 20.4% respectively. CONCLUSION: Higher levels of PSA suggest prostate cancer, but still additional parameters are needed for patients with PSA 4-20 ng/mL, such as free PSA and f/t PSA. Although a cut off level of < 0.18 for f/t PSA seems to be the most accurate one to discriminate benign and malign diseases further studies on larger groups of patients are needed.

Serum and pleural fluid levels of alpha-L-fucosidase and sialic acid have no diagnostic value in malignant pleural effusions.

The association of biological markers with cancer has been recognized for many decades. To determine whether alpha-L-fucosidase (ALF) and sialic acid (SA) are sensitive markers in malignant pleural effusions, they were investigated in serum and pleural fluid of 64 consecutive pleurisy patients, and in serum of 23 healthy subjects as a control group. The serum ALF (sALF) and serum SA (sSA) values of malignant and nonmalignant groups were higher than that of the control group, but the differences were statistically significant only for sSA determinations (p < 0.05). Values of sALF, sSA, pleural ALF (pALF), and pleural SA (pSA) were higher in the malignant group than the nonmalignant group, but no significant difference was found between the two groups. In conclusion, neither alpha-L-fucosidase nor sialic acid will be useful in the detection of malignant pleural effusions.