CO-EXISTING HASHIMOTO'S THYROIDITIS DOES NOT AFFECT BONE METABOLISM IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM.

Context: Primary hyperparathyroidism (PHPT) is often associated with thyroid disorders like nodular goiter, Hashimoto's thyroiditis (HT) and Graves' disease. Objective: Our aim was to explore whether the co-existence with HT affects bone metabolism in patients with PHPT. Design: This was a comparative cross-sectional study carried out in a tertiary inpatient endocrine center from January 2018 through December 2020. Subjects and Methods: A total of 234 patients were diagnosed with PHPT at our endocrine center. One hundred of them were included in the study - 50 with PHPT only and 50 with PHPT and HT. Two control groups were defined: 37 with HT and 37 without PHPT and HT. Serum markers of calcium-phosphate metabolism, bone markers (RANKL, Osteoprotegerin, ß-CTX, Osteocalcin) and interleukin-17A were measured. Results: The frequency of HT among patients with PHPT was 37.6% (95% CI 31-43%) and did not differ significantly from that in the general population, 32.5% (95% CI 30-35%). Age, BMI, markers of calcium-phosphate metabolism, bone markers and interleukin-17A weren't significantly different in PHPT with and without HT or between the two control groups. The participants with PHPT had higher levels of interleukin-17A, ß-CTX and Osteocalcin (p<0.05) than those without the PHPT. RANKL and Osteoprotegerin in these groups did not differ.Interleukin-17A correlated positively with serum calcium, PTH and RANKL and negatively with serum inorganic phosphate and 25(OH)D. Controlling for HT and age did not change the correlation. Conclusions: In our study, HT has not additional effect on bone metabolism in the patients with PHPT. Higher levels of interleukin-17A in PHPT suggest a possible role in the PTH-induced bone remodeling.

THYROTROPIN-RECEPTOR ANTIBODIES, IMMUNOGLOBULIN E AND ANTINUCLEAR ANTIBODIES IN PATIENTS WITH GRAVES' DISEASE AND GRAVES' ORBITOPATHY.

CONTEXT: Thyrotropin-receptor antibodies (TRAb) are biomarkers of Graves' disease (GD) and Graves' orbitopathy (GO). Elevated immunoglobulin E (IgE) and antinuclear antibodies (ANA) were also found in GD patients. OBJECTIVE: We aimed to assess TRAb, IgE and ANA in GD and GO patients and to evaluate the relationship between the immunological markers and smoking. DESIGN: This was a comparative cross-sectional study carried out in a single tertiary care center from June 2018 to January 2020. SUBJECTS AND METHODS: A total of 103 GD patients (mean age 51.2, 84 females) were divided into three subgroups: moderate-to-severe GO (n=36), mild GO (n=32) and "only GD" subgroup (n=35). Forty healthy controls (HC) (mean age 51.2, 36 females) were also included. TRAb were measured by a thyrotropin-binding inhibitory immunoglobulin (TBII) assay in GD patients; IgE and ANA - by an enzyme-linked immunosorbent assay in all subjects. RESULTS: GD patients had higher IgE-positivity rate (p=0.04) and similar ANA-positivity compared to HC. Moderate-to-severe GO subgroup had the highest TBII (p<0.01), the lowest TBII-negativity rate (p<0.01) and the highest ANA-positivity rate (p=0.03) and was the only subgroup whose IgE-positivity rate was significantly higher than HC (25% vs. 7.5%). Mild GO and "only GD" patients had comparable TBII, TBII-negativity rate, IgE and ANA.Both GO subgroups had significantly higher smoking rate than "only GD" patients. Smoking was positively associated with IgE positivity (φ=0.22, p=0.03), and negatively with TBII negativity rate (φ=-0.24, p=0.02). CONCLUSIONS: GD patients exhibit different immunological patterns depending on the presence and severity of GO. Smoking might be just one of the factors responsible for the clinical and immunological variety of GD. Further studies are needed.

ECHOCARDIOGRAPHIC MYOCARDIAL CHANGES IN ACROMEGALY: A CROSS-SECTIONAL ANALYSIS IN A TERTIARY CENTER IN BULGARIA.

CONTEXT: Cardiomyopathy is the most frequent cardiovascular complication in acromegaly. OBJECTIVE: We aimed to compare some echocardiographic markers in acromegaly patients with controls and find a correlation with disease duration, disease activity, levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). DESIGN: We conducted a cross-sectional case-control study for the period of 2008-2012. SUBJECTS AND METHODS: Acromegaly patients altogether 146 (56 men and 90 women), were divided into four groups according to disease activity and the presence of arterial hypertension (AH). The control group included 83 subjects, matching the patient groups by age, gender and presence of AH. GH was measured by an immunofluorometric method, while IGF-1 by IRMA method. All patients and controls were subjected to one- and two-dimensional transthoracic echocardiography, color and pulse Doppler. RESULTS: We found a thickening of the left ventricular walls and an increase in the left ventricular mass. However, these changes were not statistically significant in all groups and no correlation with disease duration could be demonstrated. As markers of diastolic dysfunction, increased deceleration time and isovolumetric relaxation were registered, which were dependent mainly on age in a binary logistic regression analysis, but not GH or IGF-1. Using absolute values, ejection and shortening fractions were increased in some groups. Using cut-off values, a higher percentage of systolic dysfunction was demonstrated in patients compared to their corresponding controls. Engagement of the right heart ventricle was also found - increased deceleration time and decreased e/a tric ratio. CONCLUSIONS: In conclusion, functional impairments of both ventricles were present, with a predominance of left ventricular diastolic dysfunction.

Treatment outcome results from the Bulgarian Acromegaly Database: adjuvant dopamine agonist therapy is efficient in less than one fifth of non-irradiated patients.

OBJECTIVE: We described biochemical outcome in regards to different treatment modalities in patients with acromegaly in Bulgaria. PATIENTS AND METHODS: It was a retrospective analysis using data from the Bulgarian Acromegaly Database. Patients with eligible data on at least one treatment modality were included in the study. Disease control was assessed by both GH and IGF-1 values or by GH/IGF-1 alone in cases with one marker. Last follow-up was median 7.0 (range 0.5-51) years after diagnosis. RESULTS: We identified 534 patients with interpretable data, 65.4% of whom were females. Overall surgical cure rate was 28.8%. Adjuvant bromocriptine and cabergoline treatment was analyzed in 133 and 70 patients with disease control achieved in 18.8% and 31.4% respectively. Patients without prior radiotherapy had 16.3% and 18.2% control rates respectively. Predictors of response to dopamine agonist (DA) therapy were disease activity, radiotherapy and medication dose. Adjuvant somatostatin analog (SSA) treatment led to biochemical control in 38.6% of 70 patients. Combination of SSA and cabergoline led to remission in 25% of 20 patients. Growth hormone receptor antagonist (GHRA) alone or in combination resulted in remission in 61.5% of 13 patients. Approximately one third of the patients were cured median 10 years after irradiation. Overall disease control was observed in 51.4% of our patients increasing to 70.3% in the last 5 years of the study period. CONCLUSION: DAs are efficient in less than 20% of non-irradiated patients. They are a good cost-effective alternative for carefully selected patients.

Individual risk factors of the metabolic syndrome in adult patients with growth hormone deficiency--a cross-sectional case-control study.

OBJECTIVE: Growth hormone deficiency in adults (GHDA) is considered to be associated with increased cardiovascular risk, most commonly reflected by the prevalence of the metabolic syndrome (MS). However, there are still a limited number of studies comparing directly the MS prevalence in GHD patients to that in general population. The aim of this study was to investigate the individual risk factors of the MS in a cohort of GHD patients and to compare its prevalence with an age- and sex-matched control group. DESIGN: A cross-sectional case-control study. METHODS: In total, 54 adult patients with GHD (childhood onset GHD (COGHD): n=19, adult onset GHD (AOGHD): n=35) and 2 153 control subjects were studied. GHD was diagnosed according to the Endocrine Society Clinical Practice Guideline recommendations from 2011 and MS was scored by the NCEP-ATP III definition. RESULTS: The main metabolic abnormalities in GHD group were increased waist circumference (50.0%), low HDL-cholesterol (42.6%) and hypertriglyceridemia (40.7%) and their prevalence was significantly higher (p=0.013, p=0.019 and p=0.010, respectively) than in control group, where increased blood pressure prevailed (64.2%, p<0.0001). However, the difference in the MS prevalence between the 2 groups (29.6% vs. 24.9% in controls) failed to reach statistical significance (p=0.429). Patients with MS from both groups did not differ significantly in their metabolic profile (except for increased blood pressure), mean age and gender distribution. CONCLUSIONS: Although GHDA was associated with the development of visceral obesity and dyslipidemia, these adverse cardiovascular risk factors did not determine a higher prevalence of the MS in Bulgarian GHD patients compared to control subjects. Furthermore, the individual risk factors of the MS did not significantly differ between patients with MS from both groups.

Asymmetric dimethylarginine (ADMA) and soluble vascular cell adhesion molecule 1(sVCAM-1) as circulating markers for endothelial dysfunction in patients with pheochromocytoma.

BACKGROUND: Endothelial dysfunction is a common feature of hypertension and is associated with reduced nitric oxide bioavailability. The endogenous inhibitor of nitric oxide syntase, asymmetric dimethylarginine (ADMA), and soluble adhesion molecules such as vascular cell adhesion molecule 1 (sVCAM-1) have been established as markers of endothelial dysfunction in a number of pathologic conditions including essential hypertension. There is little information, however, about these markers in endocrine hypertension. OBJECTIVE: To investigate the levels of circulating ADMA and sVCAM-1 in patients with pheochromocytoma. PATIENTS AND METHODS: Serum ADMA and sVCAM-1 concentrations were assayed by ELISA technique in 18 patients with pheochromocytoma, 18 patients with essential hypertension (EH) and 18 healthy subjects serving as a control group. RESULTS: ADMA and sVCAM-1 levels were significantly elevated in pheochromocytoma patients compared to normotensive healthy controls (0.479 ± 0.072 vs. 0.433 ± 0.054 µmol/l, p=0.037 and 690 ± 181 vs. 577 ± 108 ng/ml, p=0.03, respectively). Patients with EH also had higher ADMA concentrations than the control group, but the difference was not significant (0.476 ± 0.075 vs. 0.433 ± 0.054 µmol/l, p=0.06). No associations were found between the levels of ADMA, sVCAM-1 and some potential risk factors for endothelial dysfunction. CONCLUSION: Endothelial function is impaired in patients with pheochromocytoma as indicated by the elevated circulating levels of ADMA and sVCAM-1. The lack of association of these markers with cateholamines, glucose and lipid abnormalities together with their comparable levels in EH patients suggests that endothelial dysfunction is most likely related to hypertension itself.

Macroprolactinemia in patients with prolactinomas: prevalence and clinical significance.

BACKGROUND: Data on the prevalence of macroprolactinemia in patients with prolactinomas is quite limited as the presence of high-molecular prolactin forms is suspected mainly in subjects with mild hyperprolactinemia and negative pituitary imaging. OBJECTIVE: The main objective of this observational case-control study was to assess the prevalence and clinical significance of macroprolactinemia among patients with prolactinomas. METHODS: The study population consisted of 239 subjects: 131 prolactinoma patients and 108 sex-, age- and ethnicity- matched healthy controls. Macroprolactinemia was defined by a PRL recovery after PEG precipitation of<40%. RESULTS: The prevalence of macroprolactinemia among newly diagnosed prolactinoma patients did not differ statistically from the prevalence in the control group (3.5 vs. 3.7%; p=1.000) but was lower although non-significantly than the subgroup of patients treated with dopamine agonists (DA) (3.5 vs.10.8%; p=0.072). Significant association between disruptions of ovarian function and serum levels of the monomeric as well as high-molecular prolactin isoform was found. CONCLUSIONS: In few cases, the presence of typical hyperprolactinemia-related clinical symptoms and their disappearance after treatment with DA suggests biological activity of macroprolactin comparable with that of monomeric prolactin isoform. Decrease of macroprolactin levels after DA treatment could suggest tumoral origin of the high-molecular isoform in these rare cases. Although macroprolactinemia is considered a benign condition, pituitary imaging, DA treatment, and prolonged follow-up may be necessary in certain cases. An individualized approach to the management of patients with macroprolactinemia should be applied.

Anti-Müllerian hormone and inhibin B levels reflect altered Sertoli cell function in men with metabolic syndrome.

The aim of the present study was to investigate the Sertoli cell markers inhibin B and anti-Müllerian hormone (AMH) in men with metabolic syndrome (MS). Twenty patients with MS according to the criteria of the International Diabetes Federation and 20 non obese age-matched men were investigated. The levels of testosterone, sex hormone binding globulin (SHBG), gonadotropins, inhibin B and AMH were measured in all of them. In obese patients with MS total testosterone (15.74 ± 6.95 versus 27.84 ± 12.80 nmol l(-1), P = 0.001), SHBG (21.71 ± 11.08 versus 38.80 ± 17.51 nmol l(-1), P = 0.001) and free testosterone (430.35 ± 237.40 versus 613.85 ± 303.65 pmol l(-1), P = 0.040) were significantly lower than in the controls. Interestingly, the inhibin B (103.64 ± 56.77 versus 149.88 ± 68.31 pg ml(-1), P = 0.025) and AMH levels (30.84 ± 13.14 versus 43.14 ± 9.66 pmol l(-1), P = 0.002) were also significantly lower in MS group in comparison to the other participants. The lowest levels of AMH were found in patients with MS and carbohydrate disturbances. The decreased concentrations of testosterone, inhibin B and AMH in patients with MS could reflect an impaired Leydig and Sertoli cell function. Further studies in men with obesity, insulin resistance and diabetes type 2 could reveal more information about the interrelations between the metabolic disturbances and reproductive function in men.

Anti-Müllerian hormone in women with polycystic ovary syndrome before and after therapy with metformin.

Anti-Müllerian hormone (AMH) is largely expressed throughout folliculogenesis and its levels may represent both the quantity and quality of ovarian follicle pool. We conducted this study to evaluate the levels of AMH in women with polycystic ovarian syndrome (PCOS) before and after metformin therapy. 22 consecutive patients with PCOS and 20 healthy age-matched controls were investigated. The patients received 2 550 mg/day metformin for 6 months. Serum levels of AMH, sex hormones, insulin, blood glucose, and lipids were measured before and after metformin therapy. The basal AMH levels in patients with PCOS (42.34±6.42 pmol/l) were significantly elevated in comparison with the controls (21.58±3.41 pmol/l), p=0.008. 17 patients completed 6 months therapy with metformin. Of them, 13 responded clinically by restoration of regular menstrual cycles. The AMH levels of these 13 women decreased from 45.67±9.30 pmol/l to 38.25±6.89 pmol/l (16.27%). In the other 4 patients who did not show satisfactory clinical response to metformin, AMH levels increased from 31.30±16.52 to 80.77±12.73 (p=0.021). The patients who responded to metformin were significantly overweight, had higher BMI, waist circumference, body fat, and blood pressure as compared to nonresponders. AMH levels are significantly elevated in women with PCOS and they may serve as a marker for evaluation of treatment efficacy with metformin. Furthermore, obese PCOS patients are more likely to respond to metformin therapy with maximal doses as compared to the ones with low body mass index.

Increased plasma endothelin level as an endothelial marker of cardiovascular risk in patients with active acromegaly: a comparison with plasma homocysteine.

The aim of the present study was to evaluate the plasma endothelin-1 (ET-1) and total homocysteine (tHcy) levels as biochemical markers of endothelial dysfunction and atherosclerosis in patients with active and cured acromegaly in order to assess the relationship between the secretory status of growth hormone (GH)/insulin-like growth factor I (IGF-I) and ET-1/tHcy levels. The patients were divided in two subgroups: 1) patients with active disease (n = 30); and 2) patients with nonactive cured acromegaly (n = 21). Plasma ET-1 levels were directly determined by a highly sensitive enzyme immunoassay and plasma tHcy concentrations were measured by a fluorescence polarization immunoassay. In active acromegaly subjects, plasma ET-1 levels were 1.24 +/- 0.2 pmol/L, significantly higher than in both nonactive acromegalics (0.39 +/- 0.1 pmol/L) and age-matched healthy controls (0.49 +/- 0.2 pmol/L) (P < 0.001). Plasma tHcy concentrations, however, did not differ significantly in all studied groups: nonactive acromegalics: 9.54 +/- 4.42 micromol/L; active acromegalics: 9.0 +/- 3.14 micromol/L; and control subjects: 9.96 +/- 2.95 micromol/L (P > 0.05). In conclusion, our study demonstrated that elevated ET-1 levels probably contributed to premature atherosclerosis and cardiovascular disease and represent a new risk factor for endothelial dysfunction and early vascular complications in acromegaly. We propose that GH and IGF-I secretory status are important determinants of plasma ET-1 but not tHcy levels.

Homocysteine, renin and aldosterone in patients with Cushing's syndrome.

In the present study, we assessed the levels of fasting homocysteine in patients with active Cushing's syndrome using two different assay methods. To determine a possible link between homocysteine and renin-angiotensin-aldosterone system (RAAS), nine patients with Cushing's syndrome and nine patients with metabolic syndrome were given a 1-month treatment with angiotensin II (AII) receptor blocker valsartan. Plasma homocysteine, active renin and aldosterone did not differ significantly among patients with Cushing's syndrome, patients with metabolic syndrome and controls. As expected, active renin increased significantly during valsartan treatment in patients with Cushing's syndrome as well as in patients with metabolic syndrome. Plasma homocysteine did not change after valsartan treatment, suggesting a lack of direct relationship between homocysteine and RAAS. Our data suggest that homocysteine might not serve as a reliable marker of endogenous hypercortisolism or of cardiovascular risk associated with Cushing's syndrome and metabolic syndrome.

Melatonin-insulin interactions in patients with metabolic syndrome.

Metabolic syndrome (MS) as a group of risk factors is strongly associated with diabetes type 2 and cardiovascular disease. Insulin resistance plays a key role in the pathogenesis of MS. Recent studies have shown that melatonin may influence insulin secretion and glucose homeostasis. Therefore, the present study analyzed the relationships between the melatonin and the insulin in patients with MS and controls. The melatonin rhythm, insulin and lipid levels were studied in 40 subjects (21 patients and 19 controls) in reproductive age. The night melatonin-insulin ratio was correlated negatively with low-density lipoprotein cholesterol (r = -0.370, p = 0.024) and total cholesterol (r = -0.348, p = 0.030), and positively with high-density lipoprotein cholesterol levels (r = +0.414, p = 0.010). Night-time melatonin levels were related to night-time insulin concentrations (r = +0.313, p = 0.049). The correlation was pronounced in patients with MS (r = +0.640, p = 0.002), but did not reach statistical significance in controls (P > 0.05). In the patients with MS unlike the controls the night-day melatonin difference (%) correlated negatively with the fasting glucose (r = -0.494, p = 0.023) and positively to daily insulin (r = +0.536, p = 0.012). Our results show that melatonin-insulin interactions may exist in patients with MS, as well as relationships between melatonin-insulin ratio and the lipid profile. Pineal disturbances could influence the pathogenesis and the phenotype variations of the MS. Larger studies are needed to confirm or reject this hypothesis and to clarify the role of the melatonin in the metabolic disturbances.

Influence of ageing and some lifestyle factors on male gonadal function: a study in Bulgaria.

There are few systematic studies on the relationship between blood testosterone concentrations and the symptoms of androgen deficiency in ageing males. To assess the changes in sex hormone levels with age in relation with some lifestyle factors, the serum levels of total testosterone (TT), sex-hormone binding globulin (SHBG), luteinising hormone (LH) and follicle stimulating hormone (FSH) were measured in 33 men, age range 40-89 years. In addition, free testosterone (FT) and the free androgen index (FAI) were calculated. Seventeen healthy men under 40 years were involved as controls. The men over 40 years revealed significantly decreased TT, FT and FAI, and in the subgroup of men over 60 years, FSH and SHBG were significantly increased. Pearson's analysis showed that TT levels were significantly correlated with body mass index (BMI) (r = -0.464, P < 0.01) and body weight (r = -0.413, P < 0.05). SHBG levels were significantly correlated not only with age (r = +0.407, P < 0.05), but also with LH (r = +0.605, P < 0.001) and alcohol consumption (r = +0.382, P < 0.05). In conclusion, the TT, FT and FAI decreased in males over 40 years, but the alterations in hormone levels with age are more pronounced in men over 60 years. The important determinants of sex hormones are age, BMI and some lifestyle factors.

Disturbances in gonadal axis in women with anorexia nervosa.

UNLABELLED: Anorexia nervosa negatively affects multiple body systems including the reproductive system. AIM: To assess the disturbances in the hypothalamic-pituitary-gonadal axis (HPG) and the relationship between the gonadotropins and body weight, duration of the disease and amenorrhea we studied 40 female anorexic patients (aged 14-31 years) with a body mass index (BMI) 15.14+/-1.80 kg/m(2) and a degree of weight loss 28.67+/-8.74%. Fifteen healthy, age-matched women with normal weight served as controls. METHODS: We investigated the disturbances in the gonadotropin levels before and after stimulation with gonadotropin-releasing hormone (GnRH) 100 microg i.v. One week later 100 mg of clomiphene citrate (CC) was administered orally for 5 days. RESULTS: Basal levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were significantly lower in the patients. The responses of LH to GnRH were diminished, but those of FSH were exaggerated. However, after clomiphene citrate administration, LH increased 5.4 times whereas FSH increased 1.7 times. The basal levels of LH were significantly correlated with body weight (r=+0.373, p<0.05), BMI (r=+0.385, p<0.01) and percentage of the weight loss (r=-0.356, p<0.05). FSH levels were positively correlated with the duration of the disease (r=+0.481, p<0.01) and amenorrhea (r=+0.540, p<0.01). CONCLUSIONS: Our study demonstrates dissociation in the secretion of gonadotropins after hypothalamic stimulation in anorexic patients. It also reveals the relationship between alterations in the hormones of the HPG axis, not only with the changes in body weight, but also with the duration of the disease.

Low testosterone levels and unimpaired melatonin secretion in young males with metabolic syndrome.

The interrelations between testosterone, insulin and melatonin levels in males with metabolic syndrome (MS) are still not clarified, especially in young age groups. The aim of the present study was to compare the testosterone serum levels in young men with MS to those in healthy controls, and to determine the possible changes in their melatonin rhythm, as well as the relation between melatonin, insulin and lipid profile. Fasting insulin and testosterone concentrations were measured in 10 healthy nonobese and 10 MS patients. Blood samples for melatonin, insulin and luteinizing hormone (LH) were collected at 19.00, 03.00 and 11.00 hours. A significant difference was found between the testosterone levels in controls and patients. Luteinizing hormone levels in both groups were similar, however, higher night LH levels in MS patients were observed. No changes in the melatonin concentrations of the two groups were found. In conclusion, total testosterone levels were significantly lower in young men with MS compared with healthy age-matched controls. Mild hypoandrogenia in hyperinsulinaemic patients was not related with changes in their melatonin levels. No alterations in the endogenous melatonin rhythm of the MS patients were found.

Gender-dependent effect of ageing on peripheral insulin action.

The aim of the present study was to investigate the effect of both gender and age on insulin secretion, peripheral insulin effectiveness and insulin-receptor binding. Eighty healthy volunteers, 40 females of mean age 38.47 +/- 11.37 years and mean BMI 21.99 +/- 2.06 kg/m(2) and 40 males of mean age 34.87 +/- 11.22 years and mean BMI 22.65 +/- 2.31 kg/m(2), with normal glucose tolerance participated in the study. Peripheral insulin effectiveness was measured by the artificial endocrine pancreas, using the euglycaemic hyperinsulinaemic clamp technique and insulin-receptor binding on circulating mononuclear blood cells. Peripheral insulin sensitivity was significantly higher in females as compared to males (p < 0.001), while males demonstrated higher total number of insulin receptors (p < 0.0001) and number of high-affinity receptors (p < 0.01). Peripheral insulin sensitivity decreased with ageing in both males and females, the reduction in females being more pronounced (p < 0.05). In the group under 40 years, the females demonstrated significantly higher insulin sensitivity as compared to males (p < 0.001) and lower insulin-receptor binding. Over 40 years, females presented higher peripheral insulin sensitivity and higher insulin-receptor binding. The percentage of specifically bound insulin increased significantly with ageing in females and decreased in males. We consider that probably the higher androgen level in males affects the post-receptor processes in insulin action and despite the higher insulin-receptor binding, males have lower insulin sensitivity. The androgen levels in females increase with ageing, which could probably affect peripheral insulin sensitivity at the post-receptor level. In conclusion, our results demonstrate that when analysing peripheral insulin effectiveness and insulin-receptor binding, one should always consider both gender and age.

Markers of vascular function in hypertension due to Cushing's syndrome.

BACKGROUND: There are limited data regarding the role of vascular endothelial growth factor (VEGF) in arterial hypertension. The aim of the study was to determine some markers of vascular function, including VEGF, active renin and prostaglandin E (2) (PGE (2)) in patients with endocrine hypertension resulting from Cushing's syndrome. MATERIAL AND METHODS: The study comprised 32 patients with active Cushing's syndrome, 22 patients with essential hypertension, and 24 healthy volunteers. RESULTS: VEGF was significantly elevated in the groups of patients compared to controls. VEGF levels in the patients with Cushing's syndrome were significantly higher than in patients with essential hypertension. We did not find significant differences in VEGF levels between patients with Cushing's disease and Cushing's syndrome due to adrenal tumor. Active renin and PGE (2) levels did not differ significantly among groups. CONCLUSION: VEGF levels were significantly elevated in endocrine hypertension due to glucocorticoid excess. Higher VEGF levels were detected in patients with Cushing's syndrome compared to patients with essential hypertension. Based on our results, we could not judge the extent to which this VEGF elevation in the patients with Cushing's syndrome was due to the hypertension itself and/or to the presence of adrenal tumor/hyperplasia.

The effect of smoking on peripheral insulin sensitivity and plasma endothelin level.

OBJECTIVES: The aim of the present study was to investigate the effect of smoking on peripheral insulin effectiveness. METHODS: Seven healthy volunteers, nonsmokers, of mean age 39.6 +/- 7.1 Years and mean BMI 22.65 +/- 11.98 kg/m2, without family history of diabetes mellitus, with normal blood pressure participated in the study. All the parameters were studied twice - at baseline as well as after smoking (4 cigarettes per one hour). The study was performed in three days: at the first day we studied peripheral insulin effectiveness (M) in vivo by the artificial endocrine pancreas (Biostator), using the euglycaemic hyperinsulinaemic clamp technique, and insulin-receptor binding on circulating mononuclear blood cells; at the second day - the same parameters after one-hour smoking during the third hour of clamping; at the third day - plasma endothelin level, blood pressure and heart rate at baseline and after one-hour smoking. RESULTS: There was a significant decrease in glucose utilization during the second clamp test, when the volunteers smoked during the third hour as compared to the test at baseline (p=0.04). This was accompanied by a significant decrease in insulin receptor affinity (p=0.04). Systolic blood pressure and heart rate increased significantly after one-hour smoking (p=0.03 and p=0.001, respectively). Plasma endothelin level increased significantly after smoking (from 0.62 +/- 0.15 pg/ml to 2.05 +/- 1.67 pg/ml, p=0.03). CONCLUSION: Our results demonstrate that smoking decreases peripheral insulin sensitivity reducing insulin receptor affinity. We have confirmed that smoking increases plasma endothelin level, which probably by causing vasoconstriction and consequent tIssue hypoxaemia could decrease peripheral glucose utilization. We consider that smoking could also have a direct effect on insulin receptor affinity, thus leading to decreased peripheral insulin effectiveness.

Sibutramine in the treatment of obesity in type 2 diabetic patients and in nondiabetic subjects.

Obesity is considered a chronic disease requiring treatment. The effect of sibutramine combined with hypocaloric diet and exercise on body weight, body fat mass, lipids, glycemic control, insulin secretion and insulin resistance was evaluated in a randomized, controlled, open-label study. A total of 44 obese type 2 diabetic patients (aged 45.2+/-5.2 years, BMI 33.62+/-2.2 kg/m(2)) and 49 obese nondiabetic subjects (aged 41.9+/-5.7 years, BMI 34.3+/-2.6 kg/m(2)) were treated with sibutramine for 3 months. Moreover, 39 age-matched obese type 2 diabetic patients and 41 obese nondiabetic subjects only on hypocaloric diet and exercise served as control groups. Insulin secretion was estimated during intravenous glucose tolerance test; insulin resistance was assessed by the HOMA index. There was a significant reduction in body weight in both sibutramine-treated diabetic patients (7.1%) and nondiabetic subjects (9.1%), accompanied by a significant reduction in body fat mass. HbA1c decreased significantly in the diabetic patients after sibutramine treatment. There was a significant improvement of lipid parameters in the two groups. Insulin resistance decreased by 21.9% in the sibutramine-treated diabetic patients and by 38.5% in the nondiabetic group. Weight loss was accompanied by an increase of 43.8% in first phase insulin secretion in the sibutramine-treated diabetic group; in the treated nondiabetic subjects there was a decrease in first and second phase insulin secretion and the area under the curve for total insulin secretion. In conclusion, sibutramine leads to a significant reduction in body weight, body fat mass and waist and hip circumferences; it improves insulin sensitivity, insulin secretion, glycaemic control and lipid parameters in both diabetic and nondiabetic obese subjects.

Vascular endothelial growth factor (VEGF), prostaglandin E2(PGE2) and active renin in hypertension of adrenal origin.

There are limited data regarding the role of vascular endothelial growth factor (VEGF) in arterial hypertension. The aim of the present study was to determine some markers of vascular function, including VEGF, active renin and prostaglandin E2 (PGE2) in patients with endocrine hypertension. The study comprised: 30 patients with primary aldosteronism; 32 patients with active Cushing's syndrome; 19 patients with pheochromocytoma; 22 patients with essential hypertension and 24 healthy volunteers. VEGF was significantly elevated in all groups of patients as compared to the controls. VEGF levels in patients with Cushing's syndrome were significantly higher than those in patients with essential hypertension and primary aldosteronism. We did not find significant differences in VEGF levels between patients with Conn adenomas and idiopathic aldosteronism as well as between patients with Cushing's disease and Cushing's syndrome. PGE2 levels were not significantly different among the groups. Active renin was significantly the lowest in patients with primary aldosteronism and significantly the highest in those with pheochromocytoma compared to controls. The level of active renin in patients with primary aldosteronism was significantly lower than in patients with Cushing's syndrome and pheochromocytoma. In conclusion, VEGF levels were significantly elevated in patients with endocrine hypertension due to glucocorticoid, mineralocorticoid and/or catecholamine excess. The highest VEGF levels were detected in patients with Cushing's syndrome. The latter is associated with accelerated development of atherosclerosis and increased cardiovascular risk. VEGF might contribute to the cardiovascular risk in this disease. This effect was not likely to be PGE2 mediated.