Low catestatin as a risk factor for cardiovascular disease - assessment in patients with adrenal incidentalomas.

Background: Catestatin (Cts) is a peptide derived from proteolytic cleavage of chromogranin A, which exhibits cardioprotective and anti-inflammatory properties. Cts has been proposed as a potential biomarker for cardiovascular (CV) disease. Objectives: examining Cts in patients with incidentally discovered adrenocortical adenomas (AI), and its associations with CV risk factors and blood pressure (BP). Materials and methods: In this cross-sectional study, 64 AI patients without overt CV disease other than primary hypertension were recruited along with 24 age-, sex-, and body-mass-index (BMI)-matched controls with normal adrenal morphology. Laboratory, 24-h ambulatory BP monitoring, echocardiography, and common carotid artery sonography examinations were performed. Results: Unadjusted Cts was higher in AI patients (median 6.5, interquartile range: 4.9-37 ng/ml) versus controls (4.5 (3.5 - 28)), p=0.048, however, the difference was insignificant after adjusting for confounding variables. Cts was lower in subjects with metabolic syndrome than in those without it (5.2 (3.9- 6.9) vs. 25.7 (5.8-115) ng/ml, p<0.01), and in men compared to women (4.9 (4-7.4) ng/ml vs. 7 (4.8-100), p=0.015). AI patients in the lower half of Cts levels compared to those in the upper had a higher prevalence of hypertension (OR 0.15, 95% CI: 0.041-0.5, p<0.001) and metabolic syndrome (OR 0.15, 95% CI 0.041-0.5, p<0.001). In AI patients Cts correlated positively with high-density lipoprotein cholesterol (Spearman's r=0.31), negatively with BMI (r=-0.31), and 10-year atherosclerotic CV disease risk (r=-0.42). Conclusions: Our data indicate associations between CV risk factors and Cts. More clinical research is needed to apply serum Cts as a biomarker.

The Role of the Trabecular Bone Score in the Assessment of Osteoarticular Disorders in Patients with HFE-Hemochromatosis: A Single-Center Study from Poland.

Type 1 hereditary hemochromatosis (HH) is an autosomal, recessive genetic entity with systemic iron overload. Iron homeostasis disorders develop as a result of HFE gene mutations, which are associated with hepcidin arthropathy or osteoporosis and may cause permanent disability in HH patients despite a properly conducted treatment with phlebotomies. In this study, selected parameters of calcium and phosphate metabolism were analyzed in combination with the assessment of bone mineral density (BMD) disorders in patients from northern Poland with clinically overt HFE-HH. BMD was determined by a dual-energy X-ray absorptiometry (DXA) test with the use of the trabecular bone score (TBS) function. The study included 29 HH patients (mean age = 53.14 years) who were compared with 20 healthy volunteers. A significantly lower TBS parameter and serum 25-OH-D3 concentration, a higher concentration of intact parathormone and more a frequent occurrence of joint pain were found in HH patients compared with the control group. In HH patients, the diagnosis of liver cirrhosis was associated with lower serum 25-OH-D3 and osteocalcin concentrations. In HH, DXA with the TBS option is a valuable tool in the early assessment of the bone microarchitecture and fracture risk. A supplementation of vitamin D, monitoring its concentration, should be considered especially in HH patients with liver damage and liver cirrhosis.

Assessment of platelet function in endogenous hypercortisolism.

INTRODUCTION: It is commonly known that glucocorticoids exert a significant effect on haemostasis. Studies that have analysed the plasmatic coagulation system and fibrinolysis parameters in hypercortisolaemic patients are abundant. Platelet function, which plays a vital role in primary haemostasis, is much less clear in this context. We aimed at assessing platelet function in endogenous hypercortisolaemic patients. MATERIAL AND METHODS: Twenty-five hypercortisolaemic patients were included in the study. Twelve of them were diagnosed with overt Cushing's syndrome (OCS) and 13 had subclinical Cushing's syndrome (SCS). Thirty healthy volunteers comprised the control group. In all subjects platelet function parameters were examined: ADP- and collagen-induced platelet aggregation (ADP-IPA and Col-IPA, respectively), IMPACT R (expressed as percentage of surface covered (SC) by platelets and average size (AS) of the adhering particles in µm2), as well as closure time (CT) after platelet activation with agonists: ADP and Col or Col and epinephrine (EPI). The statistical significance level was set at 0.05. RESULTS: There was no significant difference in mean values of ADP-IPA, Col-IPA, Col/Epi CT, Col/ADP CT, SC, and AS between hypercortisolaemic subjects and controls. No statistically significant differences in means of examined parameters were found between overt and subclinical Cushing's syndrome patients. Furthermore, no statistically significant relationships were found between these parameters and hormonal indicators of hypercortisolism: 24-hour urinary cortisol excretion, morning and evening serum cortisol level, and overnight-test cortisol concentration. CONCLUSIONS: In hypercortisolaemic patients no primary haemostasis disorders are present, as reflected by platelet adhesion and ADP- and collagen-induced aggregation measurements.

Dosage and costs of lanreotide Autogel 120 mg administered as part of routine acromegaly care in Poland - two years of data from Lanro-Study.

INTRODUCTION: To evaluate, over 24 months of prospective follow-up, the dosage and costs of lanreotide AUTOGEL 120 mg (ATG120) administered as part of routine acromegaly care in Poland. MATERIAL AND METHODS: A multicentre, non-interventional, observational prospective study on resource utilisation in Polish acromegalic patients treated with ATG120 at 4-week or extended (> 4 weeks) dosing interval. The study population consisted of adult acromegalic patients treated for at least 3 injections of ATG120. The endpoints were: percentage of patients treated with ATG120 at an extended dosing interval (> 4 weeks), mean time between injections, and the cost of ATG120 during a 24-month prospective observation. Costs were calculated in PLN from the public health-care payer and patient perspective for the year 2014. RESULTS: 143 patients were enrolled in, and 132 completed (70% women, 81% macroadenoma, 75% previous surgery) the analysis. During two years, changes in the treatment pattern were reported in 41 patients: 17% of them had increased injection interval and 10% switched to octreotide LAR and then returned to ATG120. Sixty-three patients (48%) received ATG120 at an extended dosing interval. ATG120 was predominantly administered in an out-patient setting (84%) by a health care professional (97%). CONCLUSIONS: The results demonstrated that extended dosing interval of ATG120 is used in a substantial proportion of patients in routine clinical practice in Poland. Such findings support the potential for ATG120 in reducing treatment burden in the real-world clinical environment.

Assessment of real-world usage of lanreotide AUTOGEL 120 in Polish acromegalic patients - results from the prospective 12-month phase of Lanro-Study.

AIM OF THE STUDY: To assess resource utilization and costs of treatment with lanreotide AUTOGEL 120 mg (ATG120) administered as part of routine acromegaly care in Poland. MATERIAL AND METHODS: A multicentre, non-interventional, observational study on resource utilization in Polish acromegalic patients treated with ATG120 at 4 weeks or extended (> 4 weeks) dosing interval. The study recruited adult acromegalic patients treated medically for ≥ 1 year including at least 3 injections of ATG120. Data on dosing interval, aspects of administration, and resource utilization were collected prospectively during 12 months. Costs were calculated in PLN from the public health-care payer perspective for the year 2013. RESULTS: 139 patients were included in the analysis. Changes in dosing regimen were reported in 14 (9.4%) patients. Combined treatment was used in 11 (8%) patients. Seventy patients (50%) received ATG120 at an extended dosing interval; the mean number of days between injections was 35.56 (SD 8.4). ATG120 was predominantly administered in an out-patient setting (77%), by health-care professionals (94%). Mean time needed for preparation and administration was 4.33 and 1.58 min, respectively, mean product wastage - 0.13 mg. Patients were predominantly treated in an out-patient setting with 7.06 physician visits/patient/year. The most common control examinations were magnetic resonance imaging of brain and brain stem (1.36/patient/year), ultrasound of the neck (1.35/patient/year), GH (1.69/patient/year), glycaemia (1.12/patient/year), IGF-1 (0.84/patient/year), pituitary-thyroid axis hormone levels assessment (TSH-0.58/patient/year, T4-0.78/patient/year). There were 0.43 hospitalizations/patient/year. For direct medical costs estimated at PLN 50 692/patient/year the main item was the costs of ATG120 (PLN 4103.87/patient/month; 97%). The mean medical cost, excluding pharmacotherapy, was PLN 1445/patient/year (out-patient care - 49%, hospitalization - 23%, diagnostics/laboratory tests - 28%). CONCLUSIONS: These results represent the current use of ATG120 in the population of Polish acromegalic patients in a realistic clinical setting. Findings that 50% of patients could be treated with dose intervals of longer than 28 days support the potential of ATG120 to reduce the treatment burden.

Assessment of alpha1-antitrypsin and alpha2-macroglobulin levels in obese patients.

INTRODUCTION: Epidemiologic data show a higher frequency of thromboembolic incidents in obese individuals compared with normal weight subjects. Pro-inflammatory factors seem to play an important role in their development. It has not been fully explained so far how alpha1-antitrypsin (alpha1ATp) and alpha2-macroglobulin (alpha2MG) act in obese subjects. Both proteins participate directly and indirectly in regulation of inflammation, coagulation and fibrinolysis. Thus alterations in serum levels of these protease inhibitors may play an important role in the development of vascular incidents in obesity. OBJECTIVES: To assess serum alpha1ATp and alpha2MG levels in obese patients. PATIENTS AND METHODS: The study involved 16 subjects with obesity and metabolic syndrome and 14 obese subjects with no disturbances of glucose and lipid profile or arterial hypertension. 20 healthy volunteers served as the control group. Levels of alpha1ATp and alpha2MG were determined in all subjects using immunonephelometry. RESULTS: No significant differences in alpha1ATp and alpha2MG levels between the patients and the control group were observed. Comparison of the tested parameters in the obese with metabolic syndrome and those without metabolic disturbances showed higher values of alpha1ATp levels in the former group. In this group positive correlations between alpha1ATp levels and fasting insulin levels were found. CONCLUSIONS: Metabolic disturbances in obesity are associated with an elevated level of alpha1ATp, which might confirm its important role in the development of vascular incidents in obese patients. An increased risk of vascular pathological lesions in obesity is probably not associated with alpha2MG levels.

[Assessment of selected haemostatic parameters in obese patients]. / Ocena wybranych parametrów ukladu hemostazy u osób otylych.

BACKGROUND: Epidemiologic data show significantly higher frequency of thromboembolic incidents in obesity than in normal weight persons. Disorders of haemostasis seem to play a crucial role in their development. In the literature there are only few papers assessing coagulation and fibrynolitic parameters in obese subjects. AIM OF THE STUDY: Assessment of protein C (PC), antithrombin (AT) and alpha2 antiplasmin (alpha2AP) activity and thrombomodulin (TM) concentration in the blood plasma of obese person (BMI > 30 kg/m(2)). MATERIALS AND METHODS: The study involved 32 patients (22 women and 10 men, mean age 39.7 +/- 15.3 years) and 20 healthy volunteers matched correctly according to sex and age who constituted a control group. In the examined subjects activity of PC, AT, alpha2 AP were assessed by means of the colorimetric methods and TM concentration in the blood plasma using ELISA method. RESULTS: No statistically significant differences in activities of PC, AT, alpha2 AP and TM concentrations between the patients and the control group were found. However the tendency to higher activities of PC and concentrations of TM were noticed in the obese patients. Assessing tested parameters according to sex, statistically significant differences were found in AT activity between the male patients and healthy men. Statistically lower values, but still in the normal range, were found in the obese men. Comparing the groups of women, significantly lower concentrations of TM were found in the obese ones. CONCLUSIONS: It seems that changed values of PC, AT, alpha2 AP activities are not responsible for increased risk of thromboembolic events in obese persons. Increased TM concentration in obese, may indirectly indicate endothelium damage.