The effect of levothyroxine replacement therapy on lipid profile and oxidative stress parameters in patients with subclinical hypothyroid.

The purpose of this present study is to investigate the levels of oxidative stress parameters in patients with subclinical hypothyroidism (SH) and the effects of levothyroxine (LT4) replacement therapy on these parameters and lipid profile. At the beginning of the study blood samples were collected from the patients in order to analyse oxidative stress parameters, lipid profile and biochemical markers. After replacement therapy with LT4, in the third month, same tests were performed again. At the baseline superoxide dismutase (SOD) levels were found to be higher in SH patients, compared to the euthyroid group. After LT4 therapy, statistically significant decreases in SOD and catalase levels and increase in HDL-C levels were noticed. LT4 treatment was found to have positive effects on oxidative stress indicators and HDL-C levels.

Visceral adiposity index and triglyceride/high-density lipoprotein cholesterol ratio in hypogonadism

ABSTRACT Background Cardiometabolic risk is high in patients with hypogonadism. Visceral adiposity index (VAI) and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio are the practical markers of atherosclerosis and insulin resistance and independent predictors of cardiaovascular risk. To date, no study has evaluated VAI levels and TG/HDL-C ratio in hypogonadism. Subjects and methods A total of 112 patients with congenital hypogonadotrophic hypogonadism (CHH) (mean age, 21.7 ± 2.06 years) and 124 healthy subjects (mean age, 21.5 ± 1.27 years) were enrolled. The demographic parameters, VAI, TG/HDL-C ratio, asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (hs-CRP), and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured for all participants. Results The patients had higher total cholesterol (p = 0.04), waist circumference, triglycerides, insulin, and HOMA-IR levels (p = 0.001 for all) than the healthy subjects. VAI and ADMA and TG/HDL-C levels were also higher in patients than in healthy subjects (p < 0.001 for all). VAI was weakly correlated with ADMA (r = 0.27, p = 0.015), HOMA-IR (r = 0.22, p = 0.006), hs-CRP (r = 0.19, p = 0.04), and total testosterone (r = −0.21, p = 0.009) levels, whereas TG/HDL-C ratio was weakly correlated weakly with ADMA (r = 0.30, p = 0.003), HOMA-IR (r = 0.22, p = 0.006), and total testosterone (r = −0.16, p = 0.03) levels. Neither VAI nor TG/HDL-C ratio determined ADMA, HOMA-IR, and hs-CRP levels. Conclusions The results of this study demonstrate that patients with hypogonadism have elevated VAI and TG/HDL-C ratio. These values are significantly correlated with the surrogate markers of endothelial dysfunction, inflammation, and insulin resistance. However, the predictive roles of VAI and TG/HDL-C ratio are not significant. Prospective follow-up studies are warranted to clarify the role of VAI and TG/HDL-C ratio in predicting cardiometabolic risk in patients with hypogonadism.

Add on Exenatide Treatment is Beneficial in Poorly Controlled Obese Type 2 Diabetics under Intensive Insulin Regimens.

Background: Intensive insulin treatment is bothersome in obese patients with type 2 diabetes mellitus. High insulin dosages further increase weight gain and the risk of hypoglycemia. Glucagon like peptide-1 receptor agonists decrease the insulin need, cause weight loss and reduce the risk of hypoglycemia. There is limited data about the effect of exenatide on obese diabetics under intensive insulin regimens. Methods: This retrospective case series report the clinical outcomes of 23 obese (13 morbidly obese) patients with uncontrolled type 2 diabetes mellitus (Age=59±10.44 years, body mass index 41.1±6.8 kg/m2, HbA1c 9.9±1.5%), under high dose (94.1±39.6 unit) intensive insulin. Exenatide twice daily was added for a mean follow-up period of 11.22±7.01 (3-30) months. Intensive insulin regimens were continued in 7 patients while the others were switched to basal insulin during the follow-up. Results: During the follow-up, mean HbA1c levels of the patients significantly improved (p=0.019), along with the significant decrease in body mass index and the total insulin need (p<0.001 for both). Baseline insulin dosages were significantly higher in the intensive regimen group (p=0.013) while other demographical and clinical characteristics were similar. No significant difference was present between the groups regarding the alterations of HbA1c, body mass index and the reduction in total insulin dosages. Conclusion: Add on exenatide appears to be a rational treatment modality in uncontrolled obese patients with type 2 diabetes mellitus despite intensive insulin regimens. Further prospective randomized studies with longer follow-up periods are recommended.

Effect of testosterone replacement therapy on vitamin D and FGF-23 levels in congenital hypogonadism.

INTRODUCTION: Patients with hypogonadism are at increased risk of cardiac and metabolic diseases and osteoporosis. Vitamin D and Fibroblast growth factor-23 (FGF-23) play role in the regulation of bone mineral metabolism and endothelial functions. Low vitamin D levels are reported in hypogonadism, while there is no data about the effect of testosterone replacement therapy (TRT). We investigated the effect of TRT on vitamin D and FGF-23 levels along with endothelial functions and insulin resistance in hypogonadal patients. MATERIAL AND METHODS: Patients with congenital hypogonadotrophic hypogonadism (CHH) (n=32, age 20.6 ±1.58 years) were enrolled. TRT was implemented in transdermal form. The demographic parameters, FGF-23, 25(OH)D3, Asymmetric dimethylarginine (ADMA) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured both before and after TRT. RESULTS: After a follow-up period of 3.63±1.33 months, ADMA and FGF-23 levels were significantly increased (p=0.03 and p=0.005 respectively), while the 25(OH)D3 and HOMA-IR index were not significantly changed. The body mass index and waist circumference levels of the patients were also increased (p<0.001 and p=0.02) along with a significant decrease in the HDL cholesterol levels (p=0.006). CONCLUSIONS: The results show that a short term TRT increases plasma FGF-23 and ADMA levels, in young, treatment naive patients with CHH. Whether this is an early implication of TRT related adverse effects in this very young and treatment naïve population of CHH is not clear. Future prospective studies are required to find out the long-term effects of TRT on cardio-metabolic morbidity and mortality in this specific population.

Visceral adiposity index and triglyceride/high-density lipoprotein cholesterol ratio in hypogonadism.

BACKGROUND: Cardiometabolic risk is high in patients with hypogonadism. Visceral adiposity index (VAI) and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio are the practical markers of atherosclerosis and insulin resistance and independent predictors of cardiaovascular risk. To date, no study has evaluated VAI levels and TG/HDL-C ratio in hypogonadism. SUBJECTS AND METHODS: A total of 112 patients with congenital hypogonadotrophic hypogonadism (CHH) (mean age, 21.7 ± 2.06 years) and 124 healthy subjects (mean age, 21.5 ± 1.27 years) were enrolled. The demographic parameters, VAI, TG/HDL-C ratio, asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (hs-CRP), and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured for all participants. RESULTS: The patients had higher total cholesterol (p = 0.04), waist circumference, triglycerides, insulin, and HOMA-IR levels (p = 0.001 for all) than the healthy subjects. VAI and ADMA and TG/HDL-C levels were also higher in patients than in healthy subjects (p < 0.001 for all). VAI was weakly correlated with ADMA (r = 0.27, p = 0.015), HOMA-IR (r = 0.22, p = 0.006), hs-CRP (r = 0.19, p = 0.04), and total testosterone (r = -0.21, p = 0.009) levels, whereas TG/HDL-C ratio was weakly correlated weakly with ADMA (r = 0.30, p = 0.003), HOMA-IR (r = 0.22, p = 0.006), and total testosterone (r = -0.16, p = 0.03) levels. Neither VAI nor TG/HDL-C ratio determined ADMA, HOMA-IR, and hs-CRP levels. CONCLUSIONS: The results of this study demonstrate that patients with hypogonadism have elevated VAI and TG/HDL-C ratio. These values are significantly correlated with the surrogate markers of endothelial dysfunction, inflammation, and insulin resistance. However, the predictive roles of VAI and TG/HDL-C ratio are not significant. Prospective follow-up studies are warranted to clarify the role of VAI and TG/HDL-C ratio in predicting cardiometabolic risk in patients with hypogonadism.

A Rare Reason of Hyperinsulinism: Munchausen Syndrome by Proxy.

Hyperinsulinism, one of the most important causes of hypoglycaemia, can be congenital or acquired. Rarely, drug toxicity can be a reason for hyperinsulinism. In the context of Munchausen syndrome by proxy (MSP), toxicity usually occurs in children due to drug administration by a parent or caregiver. A 7-year-old girl was referred to our department due to a hyperglycaemic period and hypoglycaemic episodes. On admission, gliclazide was initiated due to her hyperglycaemia, which we attributed to maturity onset diabetes of the young. However, during follow-up, hypoglycaemic levels were detected. Despite cessation of gliclazide, hypoglycaemic seizures occurred. Even with the medications administered, hypoglycaemia could not be prevented. During follow-up, the mother's affect, characterized by anxiety and interest in her daughter's medical care, appeared discordant with the situation. Due to our suspicion of MSP, we discovered toxic levels of gliclazide in the blood and urine samples which had been sent to the toxicology laboratory to search for hypoglycaemic agents. The patient was isolated, and all medications were stopped. After isolation, her hypoglycaemia disappeared, and she became hyperglycaemic (250 mg/dl). Physicians should consider the possibility of MSP in hyperinsulinaemic patients with discordant laboratory results and clinical symptoms, even if the child's parents display great concern.

Thyrotropinoma with Graves' disease detected by the fusion of indium-111 octreotide scintigraphy and pituitary magnetic resonance imaging.

Thyroid-stimulating hormone-secreting pituitary adenoma (TSHoma) is a rare benign endocrinological tumor which produces TSH in the pituitary gland. Herein, we presented a female patient having TSHoma with Graves' disease during and just after pregnancy that we found by indium-111 octreotide scintigraphy while investigating the patient for hyperthyroidism symptoms.

Distribution of RET Mutations and Evaluation of Treatment Approaches in Hereditary Medullary Thyroid Carcinoma in Turkey.

OBJECTIVE: This retrospective multicenter study, centrally conducted and supported by the Society of Endocrinology and Metabolism of Turkey, aimed to evaluate the impact of free RET proto-oncogene testing in medullary thyroid carcinoma (MTC) patients. Surgical timing, adequacy of the treatment, and frequency of prophylactic thyroidectomy (PTx) in mutation carriers were also assessed. METHODS: Genetic testing for MTC and pheochromocytoma was conducted between July 2008 and January 2012 in 512 patients. Application forms and RET mutation analyses of these patients whose blood samples were sent from various centers around Turkey were assessed retrospectively. An evaluation form was sent to the physicians of the eligible 319 patients who had confirmed sporadic MTC, familial MTC (FMTC), multiple endocrine neoplasia type 2 (MEN2), or who were mutation carriers. Physicians were asked to give information about the surgical history, latest calcitonin levels, morbidity, mortality, genetic screening, and PTx among family members. Twenty-five centers responded by filling in the forms of 192 patients. RESULTS: Among the 319 patients, RET mutation was detected in 71 (22.3%). Cys634Arg mutation was the most prevalent mutation (43.7%), followed by Val804Met in 18 patients (25.4%), and Cys634Tyr in 6 patients (8.5%). Among 192 MTC patients, the diagnosis was sporadic MTC in 146 (76.4%), FMTC in 14 (7.3%), MEN2A in 15 patients (7.9%), and MEN2B in one patient. The number of mutation carriers among 154 apparently sporadic MTC patients was 8 (5.2%). Ten patients were submitted to PTx out of twenty-four mutation carriers at a mean age of 35±19 years. CONCLUSION: Turkish people have a similar RET proto-oncogene mutation distribution when compared to other Mediterranean countries. Despite free RET gene testing, the number of the PTx in Turkey is limited and relatively late in the life span of the carriers. This is mainly due to patient and family incompliance and incomplete family counselling.

Clinicopathologic features and prognostic factors of tall cell variant of papillary thyroid carcinoma: comparison with classic variant of papillary thyroid carcinoma.

OBJECTIVE: Tall cell variant (TCV), an aggressive form of papillary thyroid carcinoma (PTC), frequently presents with extrathyroidal disease and recurrence. The aim of this study was to evaluate the clinicopathologic features and outcomes of patients with TCV by comparing them with a larger group of patients with classic variant of papillary thyroid carcinoma (cPTC). PATIENTS AND METHODS: A total of 2500 patients with differentiated thyroid carcinoma were treated and monitored during a 23-year period (1992-2015). Of them, 2250 (90%) had PTC and 235 (9.5%) had follicular thyroid carcinoma. Of the 2250 patients, 862 (38.3%) and 70 (3.1%) had cPTC and TCV, respectively. Cases of TCV and cPTC of PTC were compared on the basis of risk factors. RESULTS: Patients with TCV were significantly older compared with cPTC patients (P<0.001). Tumor size was significantly bigger (P=0.01) and preablation thyroglobulin level was significantly higher (P<0.001) in TCV patients than in cPTC patients. The incidence of capsule invasion, extrathyroidal extension, and vascular invasion was significantly higher in TCV (P=0.003, <0.001, and 0.011, respectively). The incidence of initial lymph node metastasis was significantly higher in TCV (P<0.001). Patients with TCV were mostly at an advanced stage compared with patients with cPTC (P<0.001). Development of local or distant metastasis during the follow-up was significantly higher in TCV than in cPTC. Sex and multifocality were not statistically significant. CONCLUSION: TCV has a higher incidence of local or distant metastasis and mortality rate. Thus, it must be treated with the highest possible I ablation doses and followed up carefully.

Endothelial dysfunction, insulin resistance and inflammation in congenital hypogonadism, and the effect of testosterone replacement.

Patients with hypogonadism have poor cardiovascular and metabolic outcomes, and the effect of testosterone replacement therapy (TRT) is not clear. We investigated the presence of inflammation, insulin resistance and endothelial dysfunction in an unconfounded population of congenital hypogonadotrophic hypogonadism (CHH) and the effect of TRT on these subjects. A total of 60 patients with CHH (mean age 21.82±2.22 years) and 70 healthy control subjects (mean age 21.32±1.13 years) were enrolled. The demographic parameters, Asymmetric dimethylarginine (ADMA), TNF-like weak inducer of apoptosis (TWEAK), high sensitive C reactive protein (hs-CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured before and after TRT. The patients had higher Waist Circumferences (WC) (p=0.009), Diastolic Blood Pressures (p=0.02), Triglycerides (p=0.03), ADMA, insulin and HOMA-IR levels (p<0.001 for all) and lower TWEAK levels (p<0.001), compared to the healthy controls. After 5.56 ± 2.04 months of TRT, the patients had significantly elevated systolic blood pressures (p=0.01), body mass indexes and WC (p<0.001 and p=0.001 respectively) and decreased total and HDL cholesterol levels (p=0.032 and p<0.001 respectively). ADMA levels significantly increased (p=0.003), while the alterations in TWEAK, hsCRP and HOMA-IR were not significant. The results of the present study show that endothelial dysfunction, inflammation and insulin resistance are prevalent even in the very young subjects with CHH, who have no metabolic or cardiac problems at present. This increased cardiometabolic risk however, do not improve but even get worse after six months of TRT. Long term follow-up studies are warranted to investigate the unfavorable cardiometabolic effects of TRT.

Endothelial dysfunction and insulin resistance in young women with polycystic ovarian syndrome.

BACKGROUND/AIM: To evaluate whether there is a correlation between insulin resistance and nitric oxide-related endothelial dysfunction in patients with polycystic ovarian syndrome (PCOS). MATERIALS AND METHODS: The study was conducted with 25 young women with PCOS and 25 young healthy women, between 18 and 35 years of age. Plasma asymmetric dimethylarginine (ADMA) levels, serum nitric oxide (NO) levels, and homeostatic model assessment of insulin resistance (HOMA-IR) rates were measured in both the patient and control groups. RESULTS: Plasma ADMA levels were significantly higher in PCOS patients than in the controls (P = 0.001). Serum NO levels were significantly lower in patients than in the controls (P = 0.008). The HOMA-IR rates, accepted as an insulin resistance parameter, were significantly higher in patients than in the controls (P = 0.001). CONCLUSION: Results of the present study indicate that, independent of age, body mass index, and blood lipid profile, there is significant insulin resistance in PCOS patients. However, no correlation was found between HOMA-IR as an insulin resistance determinant and altered ADMA and NO levels. This finding may indicate that there are additional mechanisms of cardiovascular risks in PCOS patients other than insulin resistance.

[Multiplex ligation dependent probe amplification analysis of KAL1, GNRH1, GNRHR, PROK2 and PROKR2 in male patients with idiopathic hypogonadotropic hypogonadism].

INTRODUCTION: The purpose of this study was to determine the prevalence of KAL1, GNRH1, GNRHR, PROK2, and PROKR2 copy numbervariations in patients with idiopathic hypogonadotropic hypogonadism (IHH). MATERIAL AND METHODS: 86 hypogonadal males (76 diagnosed with normosmic idiopathic hypogonadotropic hypogonadism [nIHH] andten with Kallmann syndrome [KS]) and 95 healthy control individuals were studied for the presence of aforementioned genomic rearrangements,using multiplex ligation dependent probe amplification (MLPA). RESULTS: We detected that of the 86 patients, three with KS had a deletion of the KAL1 gene in exon 9, one of whom also carried a duplicationin exon 11; and three with nIHH had a duplication of the PROK2 gene in exon 3; a deletion of the GNRHR gene in exon 1; anda duplication of the same gene in exon 2, respectively. No abnormalities were found in the patient group for the PROKR2 and GNRH1genes. In addition, no genomic rearrangements were identified in the healthy control individuals for the described genes. CONCLUSIONS: Defining the genetic basis of disease is essential to improve our understanding of this complex disorder, and could be usefulfor genetic counselling and for directing therapy. In addition, discovering the association between genetic mutations and disease isimportant for our better understanding of normal reproductive functions.

Effects of three different medications on metabolic parameters and testicular volume in patients with hypogonadotropic hypogonadism: 3-year experience.

INTRODUCTION: The aim of this study was to demonstrate the influences of three different treatment strategies on biochemical parameters and testicular volume (TV) in patients with idiopathic hypogonadotropic hypogonadism (IHH). SUBJECTS DESIGN AND METHODS: Seventy-seven never-treated patients with IHH and age and body mass index (BMI)-matched 42 healthy controls were analysed in a retrospective design. Twenty-eight patients were treated with testosterone esters (TE), 25 patients were treated with human chorionic gonadotropin (hCG) and 24 patients were treated with testosterone gel (TG). Biochemical parameters, tanner stages (TS) and TV were evaluated before and after 6 months of treatment. RESULTS: Pretreatment TV, TS and biochemical test results were similar among the three treatment subgroup. In the TE-treated group, BMI, haemoglobin, haematocrit, creatinine, triglyceride, total testosterone (TT), TS and TV increased, but HDL-cholesterol (C) and urea level decreased significantly. In the hCG-treated group, triglyceride level decreased, and luteinizing hormone level, TS and TV increased significantly. BMI, TT, TS and TV increased, and leucocyte count, total-C, HDL-C levels decreased significantly in the TG-treated patients. No treatment type resulted in any changes in insulin resistance markers. CONCLUSION: hCG treatment resulted in favourable effects particularly on TV and lipid parameters. When TV improvement is considered less important, TG treatment may be a better option for older patients with IHH because of its easy use, neutral effects on triglyceride, haemoglobin and haematocrit, and its beneficial effects on total cholesterol level.

High plasma level of long Pentraxin 3 is associated with insulin resistance in women with polycystic ovary syndrome.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is characterized by insulin resistance. Chronic low-grade inflammation has been anticipated to play role in the pathogenesis of both insulin resistance and atherosclerosis. Pentraxin 3 (PTX3) is an inflammatory mediator synthesized in a variety of cells and tissues including heart, vascular endothelial cells, macrophages and adipocytes. In the present study, serum PTX3 level and its relationship with insulin resistance were investigated in patients with PCOS. MATERIALS AND METHODS: Forty patients with PCOS and 40 age- and body mass index (BMI)-matched healthy controls were enrolled in the study. PTX3 and high-sensitivity C-reactive protein (hs-CRP) levels were determined by enzyme immunoassay (EIA). Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula. RESULTS: Plasma levels of PTX3, hs-CRP and HOMA-IR scores were all significantly higher (p = 0.021, p = 0.002 and p = 0.0001, respectively) in women with PCOS compared with healthy controls. Blood PTX3 level correlated positively with hs-CRP, BMI, waist-to-hip ratio (WHR), HOMA-IR and negatively with high-density lipoprotein cholesterol level (p < 0.05, for all). After adjustment for age and BMI, PTX3, total testosterone levels and BMI remained as independent predictors of HOMA-IR scores (p < 0.05, for all). CONCLUSION: PTX3 level is increased in patients with PCOS in concordance with insulin resistance.

Prolactin levels, endothelial dysfunction, and the risk of cardiovascular events and mortality in patients with CKD.

BACKGROUND AND OBJECTIVES: Both prolactin clearance and production are altered in CKD. In nonrenal populations, emerging evidence suggests that prolactin participates in the atherosclerotic process. Given the elevated cardiovascular risk of CKD, this study examined links between prolactinemia, vascular derangements, and outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This observational study was conducted in two cohorts: one with 457 nondialyzed CKD patients (mean age 52±12 years; 229 men) with measurements of flow-mediated dilation (FMD) and carotid intima-media thickness and one with 173 hemodialysis patients (65±12 years; 111 men) with measurements of pulse wave velocity (PWV). Patients were followed for cardiovascular events (n=146, nondialyzed cohort) or death (n=79, hemodialysis cohort). RESULTS: Prolactin levels increased along with reduced kidney function. Prolactin significantly and independently contributed to explain the variance of both FMD (in nondialyzed patients) and PWV (in hemodialysis patients), but not intima-media thickness. In Cox analyses, the risk of cardiovascular events in nondialyzed patients increased by 27% (hazard ratio [HR], 1.27; 95% confidence interval [95% CI], 1.17-1.38) for each 10 ng/ml increment of prolactin. Similarly, the risk for all-cause and cardiovascular mortality in hemodialysis patients increased by 12% (HR, 1.12; 95% CI, 1.06-1.17) and 15% (HR, 1.15; 95% CI, 1.08-1.21), respectively. This was true after multivariate adjustment for confounders and after adjustment within the purported causal pathway (FMD or PWV). CONCLUSIONS: Prolactin levels directly associated with endothelial dysfunction/stiffness and with increased risk of cardiovascular events and mortality in two independent cohorts of CKD patients.

The relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy.

OBJECTIVES: Diabetic nephropathy (DN) is a major manifestation of microangiopathy in patients with Diabetes Mellitus (DM). Inflammation is one of the major factors in the formation of endothelial dysfunction. Endothelial dysfunction is a major contributor to the complications of DM. The aim of the present study was to investigate the possible relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy. MATERIALS AND METHODS: Plasma TNF-α and IL-6, pro-inflammatory cytokines, concentrations were measured in 25 patients with DN and in 30 diabetic control subjects. Also, we evaluated the markers of endothelial dysfunction such as flow mediated dilatation (FMD), nitrate-mediated dilatation (NMD) and carotid intima-media thickness (CIMT). RESULTS: TNF-α, IL-6 and high-sensitivity C-reactive protein concentrations were significantly higher (p = 0.012, p = 0.006 and p < 0.001, respectively) in the patients with DN than the controls. And, urinary protein concentrations were significantly higher (p < 0.001) but eGFR levels were significantly lower (p < 0.001) in the patients with DN. FMD was significantly lower in DN patients (p < 0.001). We have observed that FMD correlated negatively with body mass index (r = -0.424, p < 0.05). And there was also a positive correlation between TNF-α and urinary protein concentrations in the patients with DN (p < 0.05). CONCLUSION: TNF-α, IL-6, hsCRP and urinary protein concentrations are higher in the DN patients. There were no correlations among pro-inflammatory cytokines concentrations and markers of vascular endotelial disfunction. These findings did not show vascular endothelial dysfunction, but may indicate glomerular endothelial dysfunction.

Endogenous testosterone, endothelial dysfunction, and cardiovascular events in men with nondialysis chronic kidney disease.

BACKGROUND AND OBJECTIVES: Deterioration of kidney function impairs testosterone production, with hypogonadism being common in men with chronic kidney disease (CKD). In nonrenal populations, testosterone is suggested to participate in the atherosclerotic process. In male dialysis patients, we showed that low testosterone increases the risk of mortality. We here studied plausible links among testosterone levels, vascular derangements, and cardiovascular events in nondialysis CKD men. DESIGN, SETTING, PARTICIPANTS, & METHODS: This was a cross-sectional analysis in which flow-mediated dilation (FMD) was assessed in 239 CKD male patients (stages 1 to 5; mean age 52 ± 12 years), together with routine measurements, serum total and free testosterone, and follow-up for cardiovascular outcomes. RESULTS: Total and free testosterone levels decreased in parallel with the reduction of kidney function. Multiple regression analyses showed that total and free testosterone significantly and independently contributed to explain the variance of FMD. After a median follow-up of 31 months (range 8 to 35 months), 22 fatal and 50 nonfatal cardiovascular events occurred. In Cox analysis, the risk of cardiovascular events was reduced by 22% for each nanomole-per-liter increment of total testosterone. This reduced risk persisted after adjustment for age, renal function, diabetes mellitus, previous cardiovascular history, C-reactive protein, albumin, and FMD. The same was true for free testosterone concentrations. CONCLUSIONS: The reduction in endogenous testosterone levels observed with progressive CKD was inversely associated with endothelial dysfunction and exacerbated the risk of future cardiovascular events in nondialysis male CKD patients.

Electrophysiological assessment of the autonomic nervous system in male patients with acromegaly.

BACKGROUND/AIMS: We aimed to electrophysiologically evaluate the autonomic function in acromegalic patients using sympathetic skin response (SSR) as a reflection of the sympathetic sudomotor activity and RR interval variation (RRIV) as an indicator of the cardiovagal autonomic function. METHODS: The study group consisted of 18 male acromegalics, and the control group was composed of 18 age- and sex-matched healthy subjects. Participants underwent SSR and RRIV tests. Beginning latencies and amplitudes of the median and tibial SSRs were compared among the groups. The RRIV values recorded at rest and during hyperventilation were compared among the patients and controls. RESULTS: Latencies of SSRs recorded from the palms (median) and soles (tibial) of acromegalics were significantly longer than in healthy subjects (p = 0.004, p < 0.001). The amplitude of SSR recorded from the sole (tibial) was significantly decreased (p = 0.028). The RRIVs obtained from acromegalics at rest and during hyperventilation were significantly decreased compared with those of controls (p < 0.001). The RRIVs obtained from controls prolonged significantly during hyperventilation (p < 0.001); however, in the acromegaly group, hyperventilation did not cause a significant change in RRIV (p = 0.983). CONCLUSIONS: The present study suggests that an autonomic dysfunction exists in patients with acromegaly. Dysautonomia in acromegalics may be documented by means of SSR and RRIV.

Chitotriosidase activity predicts endothelial dysfunction in type-2 diabetes mellitus.

The enzyme chitotriosidase (ChT) is secreted by activated macrophages and play active role in human immune response. ChT activity is increased in atherosclerosis in association to the extent of the disease. We investigated the relevance of ChT to endothelial functions and insulin resistance in patients with T2DM. Forty newly diagnosed and untreated patients with T2DM (male 17; age 47.0 ± 6.2 years) and 50 healthy volunteers (male 21; age 50.2 ± 8.8 years) were enrolled. Plasma asymmetric dimethyl arginine (ADMA) levels were determined by ELISA. ChT activity was measured by the fluorescence method. Insulin resistance was calculated by the HOMA-IR formula. The patients had higher systolic blood pressures, HOMA-IR, ADMA levels, and ChT activities (P < 0.001 for all) and lower HDL cholesterol levels (P = 0.03) than the control group. The ChT activities of the total group were significantly correlated to the age (r = 0.031, p = 0.003), ADMA (r = 0.22, p = 0.04), and plasma glucose levels (r = 0.27, p = 0.01). ChT was the independent determinant of the plasma ADMA levels (r = 0.26, p = 0.02). The results of this study show that serum ChT activity is increased in patients with newly diagnosed, untreated, and uncomplicated patients with T2DM. The results also imply that increased ChT activity may be a predictor of endothelial dysfunction.