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.

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.

The relationship between acquired premature ejaculation and metabolic syndrome: a prospective, comparative study.

The aim of this study was to investigate the relationship between metabolic syndrome (MetS) and acquired premature ejaculation (PE). A total of 100 patients with acquired PE and 100 control cases were enrolled in the study. After obtaining a detailed medical history, anthropometric (weight, height and waist circumference) and blood pressure measurements were performed. Ejaculation and erection functions were evaluated by Premature Ejaculation Diagnostic Tool (PEDT) and International Index of Erectile Function-5 (IIEF-5), respectively. Self-estimated intravaginal ejaculatory latency time (IELT) of the participants was recorded. Fasting blood samples were taken for biochemical and hormonal work-up. The median PEDT scores were 16 (9-22) and 4.5 (2-8) in acquired PE and control groups, respectively (P<0.001). The mean estimated IELT values in PE patients and controls were 36.1±46.5 versus 488.2±313.8 s (P<0.001). MetS was diagnosed in 51 patients (51%) in the PE group and 24 (24%) participants in the control group (P<0.001). A significant negative correlation was observed between the components of MetS and estimated IELT, except for diastolic blood pressure. Moreover, there was a significant positive correlation between the all components of MetS and total PEDT score, except for fasting blood glucose and high-density lipoprotein cholesterol (HDL) levels. Logistic regression analysis revealed that, except blood pressure and HDL levels, MetS components were significant risk factors for PE after adjusting for age and total testosterone. In conclusion, MetS is associated with acquired PE.

The relationship between the second-to-fourth digit ratios and lifelong premature ejaculation: a prospective, comparative study.

To investigate the relationship between the fetal androgen exposure and lifelong premature ejaculation by using the ratio of the second (index)-to-fourth (ring) digits (2D : 4D) which is the marker for higher prenatal androgen exposure. Totally 65 patients with lifelong premature ejaculation and 65 control cases without any ejaculatory complaints were enrolled in the study. A detailed medical history was obtained and self-estimated intravaginal ejaculatory latency times were recorded. Ejaculation function was evaluated by Premature Ejaculation Diagnostic Tool. The lengths of the second and fourth digits of both hands were measured and 2D : 4Ds were calculated. The mean 2D : 4D values were 0.964 ± 0.024 vs. 0.978 ± 0.032 (p = 0.004) for the right hand and 0.966 ± 0.023 vs. 0.979 ± 0.032 (p = 0.006) for the left hand in lifelong premature ejaculation and control groups, respectively. Significant correlations were observed between the digit ratios and self-estimated intravaginal ejaculatory latency time (r = 0.258, p = 0.003 for right hand; r = 0.240, p = 0.06 for left hand), and between the digit ratios and total Premature Ejaculation Diagnostic Tool scores (r = -0.263, p = 0.003 for right hand; r = -0.238, p = 0.06 for left hand). Individuals with lower digit ratios have higher risks of shorter intravaginal ejaculatory latency times. These results suggest that increased fetal androgen exposure may be a new risk factor for the development of lifelong premature ejaculation.

A possible connection between tumor necrosis factor alpha and adropin levels in polycystic ovary syndrome.

CONTEXT: Adropin is a peptide hormone implicated in the regulation of insulin sensitivity and energy homeostasis. Polycystic ovary syndrome (PCOS) is a metabolic and reproductive disease associated with insulin resistance. It has been demonstrated that various inflammatory markers increased in PCOS including TNF-α. TNF-α regulates the secretion of certain peptides which play a crucial role in glucose and lipid homeostasis. There is also some evidence of a link between TNF-α and adropin. OBJECTIVE: To ascertain whether there is an association between circulating adropin levels and TNF-α in PCOS. PATIENTS AND DESIGN: 152 women with PCOS and 152 age- and body mass index-matched controls without PCOS were recruited for this cross-sectional study. MAIN OUTCOME MEASURES: Adropin and TNF-α levels were measured using ELISA. RESULTS: Adropin levels were lower in the PCOS group compared with the control group (7.43 ± 0.79 vs. 9.42 ± 0.76 ng/ml, P < 0.001), whereas TNF-α levels were higher (49.93 ± 3.39 vs. 35.83 ± 2.47 pg/ml, P < 0.001). A strongly negative correlation was found between circulating adropin levels and TNF-α levels in women with PCOS (r = -0.407, P < 0.001). Binary logistic regression analysis revealed that decreased adropin levels were significantly associated with high odds of having PCOS, although, after adjustment for TNF-α, this link vanished. Additionally, multiple linear regression analysis showed that HOMA-IR and TFN-α independently predicted adropin levels. CONCLUSIONS: Serum adropin levels are significantly decreased in PCOS and are inversely associated with TNF-α. Further dissection of the nature of this association can open new therapeutic options for metabolic diseases.

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.