Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors : A Cross-Sectional Multicenter Study.

BACKGROUND: Benign adrenal tumors are commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion (MACS) is regularly diagnosed, but its effect on cardiometabolic disease in affected persons is ill defined. OBJECTIVE: To determine cardiometabolic disease burden and steroid excretion in persons with benign adrenal tumors with and without MACS. DESIGN: Cross-sectional study. SETTING: 14 endocrine secondary and tertiary care centers (recruitment from 2011 to 2016). PARTICIPANTS: 1305 prospectively recruited persons with benign adrenal tumors. MEASUREMENTS: Cortisol excess was defined by clinical assessment and the 1-mg overnight dexamethasone-suppression test (serum cortisol: <50 nmol/L, nonfunctioning adrenal tumor [NFAT]; 50 to 138 nmol/L, possible MACS [MACS-1]; >138 nmol/L and absence of typical clinical Cushing syndrome [CS] features, definitive MACS [MACS-2]). Net steroid production was assessed by multisteroid profiling of 24-hour urine by tandem mass spectrometry. RESULTS: Of the 1305 participants, 49.7% had NFAT (n = 649; 64.1% women), 34.6% had MACS-1 (n = 451; 67.2% women), 10.7% had MACS-2 (n = 140; 73.6% women), and 5.0% had CS (n = 65; 86.2% women). Prevalence and severity of hypertension were higher in MACS-2 and CS than NFAT (adjusted prevalence ratios [aPRs] for hypertension: MACS-2, 1.15 [95% CI, 1.04 to 1.27], and CS, 1.37 [CI, 1.16 to 1.62]; aPRs for use of ≥3 antihypertensives: MACS-2, 1.31 [CI, 1.02 to 1.68], and CS, 2.22 [CI, 1.62 to 3.05]). Type 2 diabetes was more prevalent in CS than NFAT (aPR, 1.62 [CI, 1.08 to 2.42]) and more likely to require insulin therapy for MACS-2 (aPR, 1.89 [CI, 1.01 to 3.52]) and CS (aPR, 3.06 [CI, 1.60 to 5.85]). Urinary multisteroid profiling revealed an increase in glucocorticoid excretion from NFAT over MACS-1 and MACS-2 to CS, whereas androgen excretion decreased. LIMITATIONS: Cross-sectional design; possible selection bias. CONCLUSION: A cardiometabolic risk condition, MACS predominantly affects women and warrants regular assessment for hypertension and type 2 diabetes. PRIMARY FUNDING SOURCE: Diabetes UK, the European Commission, U.K. Medical Research Council, the U.K. Academy of Medical Sciences, the Wellcome Trust, the U.K. National Institute for Health Research, the U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.

Resistin is Associated with Inflammation and Renal Function, but not with Insulin Resistance in Type 2 Diabetes.

The aim of the study was to investigate the association of adipokines (resistin, leptin and adiponectin) with obesity, insulin resistance (IR) and inflammation in type 2 diabetes mellitus (T2DM). A total of 284 patients with T2DM were included. Concentrations of resistin, leptin, adiponectin, and inflammatory markers [high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6)] were measured and homeostatic model assessment for IR (HOMA-IR) index was calculated. Resistin correlated negatively with estimated glomerular filtration rate (eGFR) and positively with hsCRP, TNF-α, IL-6, and white blood cell count (WBC). Leptin correlated positively with HOMA-IR, whereas adiponectin correlated negatively. Leptin also correlated positively with body mass index (BMI), waist circumference, IL-6, WBC and negatively with eGFR. Adiponectin correlated negatively with waist circumference, WBC, and eGFR. Multivariate logistic regression indicated lower eGFR and higher WBC and IL-6 as independent predictive factors of resistin concentration above the upper quartile (CAQ3), whereas female sex and higher BMI and HOMA-IR of leptin CAQ3, and lower HOMA-IR and older age of adiponectin CAQ3. In conclusion, in contrast to leptin and adiponectin, in T2DM patients, resistin is not associated with BMI and IR, but with inflammation and worse kidney function.

Are adipokines associated with atrial fibrillation in type 2 diabetes?

INTRODUCTION: The potential effect of adipokines on the development of AF is yet to be established. The aim of this study was to investigate the association of baseline serum adipokines with 1) the presence of AF at baseline and 2) future risk of AF development. MATERIAL AND METHODS: The current study is a sub-analysis of the prospective, randomised AVOCADO (Aspirin Vs./Or Clopidogrel in Aspirin-resistant Diabetics inflammation Outcomes) trial. The AVOCADO study included patients with type 2 DM burdened with at least two additional cardiovascular risk factors and receiving acetylsalicylic acid. In patients included in the current analysis adipokines and inflammatory biomarker levels were measured. Information on the subsequent AF diagnosis was collected after a median of 5.4 years of follow-up. RESULTS: A total of 273 patients with type 2 DM (median age 68 years; 52% male) were included in the initial analysis comparing patients with and without AF at baseline. Patients with diagnosed AF (12%) had higher levels of serum resistin [8.5 (5.8-10.5) vs. 6.9 (5.6-8.7) ng/mL; p = 0.034], adiponectin [6.9 (5.6-8.7) vs. 2.7 (1.8-4.2) ng/mL; p = 0.032], and N-terminal pro-B-type natriuretic peptide [336 (148-473) vs. 108 [45-217]; p < 0.001) than non-AF patients. There were no significant differences in serum leptin, IL-6, and TNF-alpha concentrations between the two groups. From subjects without known AF at study entry, 19% developed AF at follow-up. In logistic regression analysis, baseline adipokine levels did not predict AF development. CONCLUSION: In type 2 DM, patients with AF have higher resistin and adiponectin concentrations than patients with no AF. None of the studied adipokines proved a predictor of future AF development.

Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINE-ACT study: a prospective test validation study.

BACKGROUND: Cross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC. METHODS: We did a prospective multicentre study in adult participants (age ≥18 years) with newly diagnosed adrenal masses. We assessed the accuracy of diagnostic imaging strategies based on maximum tumour diameter (≥4 cm vs <4 cm), imaging characteristics (positive vs negative), and urine steroid metabolomics (low, medium, or high risk of ACC), separately and in combination, using a reference standard of histopathology and follow-up investigations. With respect to imaging characteristics, we also assessed the diagnostic utility of increasing the unenhanced CT tumour attenuation threshold from the recommended 10 Hounsfield units (HU) to 20 HU. FINDINGS: Of 2169 participants recruited between Jan 17, 2011, and July 15, 2016, we included 2017 from 14 specialist centres in 11 countries in the final analysis. 98 (4·9%) had histopathologically or clinically and biochemically confirmed ACC. Tumours with diameters of 4 cm or larger were identified in 488 participants (24·2%), including 96 of the 98 with ACC (positive predictive value [PPV] 19·7%, 95% CI 16·2-23·5). For imaging characteristics, increasing the unenhanced CT tumour attenuation threshold to 20 HU from the recommended 10 HU increased specificity for ACC (80·0% [95% CI 77·9-82·0] vs 64·0% [61·4-66.4]) while maintaining sensitivity (99·0% [94·4-100·0] vs 100·0% [96·3-100·0]; PPV 19·7%, 16·3-23·5). A urine steroid metabolomics result indicating high risk of ACC had a PPV of 34·6% (95% CI 28·6-41·0). When the three tests were combined, in the order of tumour diameter, positive imaging characteristics, and urine steroid metabolomics, 106 (5·3%) participants had the result maximum tumour diameter of 4 cm or larger, positive imaging characteristics (with the 20 HU cutoff), and urine steroid metabolomics indicating high risk of ACC, for which the PPV was 76·4% (95% CI 67·2-84·1). 70 (3·5%) were classified as being at moderate risk of ACC and 1841 (91·3%) at low risk (negative predictive value 99·7%, 99·4-100·0). INTERPRETATION: An unenhanced CT tumour attenuation cutoff of 20 HU should replace that of 10 HU for exclusion of ACC. A triple test strategy of tumour diameter, imaging characteristics, and urine steroid metabolomics improves detection of ACC, which could shorten time to surgery for patients with ACC and help to avoid unnecessary surgery in patients with benign tumours. FUNDING: European Commission, UK Medical Research Council, Wellcome Trust, and UK National Institute for Health Research, US National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.

Resistin is a prognostic factor for death in type 2 diabetes.

PURPOSE: To investigate the association of leptin, resistin, and tumour necrosis factor α (TNF-α) with prognosis in type 2 diabetes (T2D). METHODS: Analysis included 284 T2D patients. Apart from routine laboratory parameters, baseline leptin, resistin, and TNF-α concentrations were measured. Patients were followed for a median of 5.4 years. The primary endpoint was all-cause death at follow-up. The secondary endpoint was a composite of death, acute coronary syndrome, and stroke or transient ischemic attack. RESULTS: At baseline, median age was 68 years, and 48% of patients were female. Data on the primary endpoint were obtained for all patients: 32 (11%) died during follow-up. Data on the secondary endpoint were available for 230 patients, of whom 45 (20%) reached the secondary endpoint. In univariate analyses, older age, heart failure, lower-glomerular filtration rate, and higher resistin, TNF-α and NT-proBNP concentrations were predictors of the study endpoints. Of these variables, only resistin remained an independent predictor of both study endpoints in multivariate models. In receiver-operating characteristic analysis, area under the curve for resistin was 0.7. Resistin concentration of greater than or equal to 11.4 ng/mL had sensitivity of 41% and specificity of 91% for prediction of death at follow-up (Youden's index). CONCLUSIONS: Higher resistin is associated with reduced survival in T2D, irrespectively of TNF-α. Resistin concentration of above 11 ng/mL indicates T2D patients at an increased risk of unfavourable outcomes. Leptin was not a prognostic factor. These results suggest that in T2D, association of resistin with unfavourable outcomes might, at least in part, result from its pro-inflammatory properties.

Novel biochemical predictors of unfavorable prognosis for stable coronary disease.

Successful risk stratification is necessary for optimum management of patients after acute coronary syndrome (ACS). The aim of the study was to evaluate the role of novel biochemical markers in the prediction of adverse cardiovascular events in stable patients several years after ACS.The study group was randomly selected from all ACS patients treated with reperfusion therapy between 2002 and 2003 at 1st Department of Cardiology, Medical University of Warsaw, Poland. All patients were readmitted to hospital between 2010 and 2011 for clinical and biochemical cardiovascular risk factors assessment and were prospectively observed for 30-months follow-up. The primary endpoint was all-cause death or hospital readmissions due to a cardiovascular condition at 30 months. The secondary endpoint was a composite of all-cause death or hospitalization-related noncardiovascular condition during the follow-up.The study population consisted of 146 patients (mean age 66.6 ±â€Š9.8 years; 60 female). The primary and secondary endpoints occurred in 49 and 65 patients, respectively. Univariate analysis demonstrated that out of 17 analyzed biomarkers only high-sensitive C-reactive protein (hsCRP), Soluble Fms-Like Tyrosine kinase-1 (sFlt-1), and endothelin-1 (ET-1) were significantly associated with primary end-point and N-Terminal pro-B-type natriuretic peptide (NT-proBNP), hsCRP, ET-1, sFlt-1, and procalcitonin (PCT)-with secondary end-point. Multivariate analysis demonstrated that concentration of sFlt-1 was the only independent factor associated with primary end-point (P = .007 and P = .025, respectively), whereas NT-proBNP and hsCRP levels were only associated with secondary end-point (P = .004 and P = .001, respectively).sFlt-1, NT-proBNP, and hsCRP are associated with adverse outcomes in stable patients several years after ACS and may emerge as useful clinical biomarkers to enhance stratify patient's risk.

Total testosterone to dihydrotestosterone ratio assessed by LC-MS/MS predicts a worse metabolic profile not only in PCOS patients.

OBJECTIVES: Total testosterone/dihydrotestosterone ratio (TT/DHT) was found to determine metabolic risk in polycystic ovary syndrome (PCOS). The aim of this study was to analyze whether (TT/DHT) may be helpful in predicting metabolic risk not only in PCOS patients but also in healthy women. MATERIAL AND METHODS: Total testosterone (TT), dihydrotestosterone (DHT), androstendione and dehydroepiandrosterone sulphate (DHEA-S) were measured by LC-MS/MS in 36 women with PCOS and in 29 age-matched controls without clinical hyperandrogenism. In all participants, anthropometric data, lipids, adipose tissue percent (%fat), HOMA-IR were also assessed. RESULTS: The studied groups were not different in terms of age, BMI, waist circumference, %fat and HOMA-IR. In the patients group, mean TT and androstendione levels were significantly higher as compared to controls (1.4 nmol/L vs. 1.0 nmol/L, P < 0.001) and (6.6 nmol/L vs. 4.9 nmol/L, P < 0.01), respectively. In the patients group, mean TT/DHT ratio was significantly higher compared to controls (3.6 vs. 2.7, P < 0.01) and correlated with BMI (r = 0.37, P < 0.05), waist circumference (r = 0.44, P < 0.01), %fat (r = 0.30, P < 0.05), as well as with insulin levels (r = 0.38, P < 0.05) and HOMA-IR (r = 0.44, P < 0.05). The association between TT/DHT ratio and unfavorable metabolic parameters was also seen in controls. CONCLUSION: Total testosterone/dihydrotestosterone ratio assessed by LC-MS/MS correlates with a worse metabolic profile not only in PCOS patients, but also in healthy women.

HLA DQ2 HAPLOTYPE, EARLY ONSET OF GRAVES DISEASE, AND POSITIVE FAMILY HISTORY OF AUTOIMMUNE DISORDERS ARE RISK FACTORS FOR DEVELOPING CELIAC DISEASE IN PATIENTS WITH GRAVES DISEASE.

OBJECTIVE: The diagnosis of celiac disease (CD) in patients with different autoimmune diseases including Graves disease (GD) remains a challenge. The aims of our study were to: (1) assess the prevalence of CD in Polish patients with GD and (2) evaluate the prevalence of CD in the subgroups of patients with GD divided on the basis of clinical and human leukocyte antigen (HLA) typing criteria. METHODS: The prospective study was conducted at an academic referral center. The study groups consisted of consecutive, euthyroid patients with GD (n = 232) and healthy volunteers without autoimmune thyroid diseases (n = 122). The diagnosis of CD was based on elevated immunoglobulin A autoantibodies to the enzyme tissue transglutaminase (IgA-TTG) and small intestine biopsy findings. RESULTS: CD was diagnosed in 8 patients with GD (3.4%) and 1 healthy volunteer (0.8%). The development of CD in patients with GD was strongly associated with HLA-DQ2 haplotype (as predicted from linkage disequilibria, 14.6% vs. 1.5%, P = .009; odds ratio [OR] = 11.3; 95% confidence interval [CI] 1.3-252.7): 6 patients with CD carried HLA-DRB1(*)03, 1 carried an HLA-DRB1(*)04 allele, and 1 had an HLA-DRB1(*)07/(*)11 genotype. Multivariate analysis showed independent associations between CD and early GD onset (P = .014, OR = 9.6), autoimmunity in family (P = .029, OR = 6.3) and gastroenterologic symptoms (P = .031, OR = 8.1). CONCLUSIONS: The results of our study suggest that serologic screening for CD may be considered in GD patients (1) with the HLA alleles typical for CD, (2) with an early onset of GD, or (3) a family history of autoimmunity. Moreover, the diagnosis of CD should be explored in euthyroid GD patients with nonspecific gastrointestinal symptoms.

Association of adipokines and inflammatory markers with lipid control in type 2 diabetes.

INTRODUCTION: Data regarding the effect of certain adipokines on lipid metabolism are equivocal. OBJECTIVES: The aim of this study was to evaluate the association of lipid control with adipokines and inflammatory markers in patients with type 2 diabetes. PATIENTS AND METHODS: The analysis included 195 patients with type 2 diabetes. The achievement of treatment targets in terms of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides was assessed in accordance with the current guidelines. Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index as well as concentrations of highmolecular-weight (HMW) adiponectin, leptin, resistin, high-sensitivity C-reactive protein, interleukin 6, and tumor necrosis factor α (TNF-α) were measured in all patients. Logistic regression analyses were performed to determine the risk factors for inadequate lipid control. RESULTS: Optimal control in terms of total cholesterol, LDL, HDL, and triglycerides was achieved in 61%, 43%, 53%, and 68% of the patients, respectively. In multivariate analyses, female sex, lower resistin concentrations, and the absence of statin treatment were predictors of total cholesterol levels above the treatment target; older age and lower statin dose--of LDL cholesterol levels above the treatment targets; female sex, higher HOMA-IR index, lower HMW adiponectin concentrations, and higher TNF-α concentration-o-f HDL levels below the treatment targets; and higher HOMA-IR, lower HMW adiponectin concentration, and the absence of statin treatment--of triglycerides above the treatment target. CONCLUSIONS: In type 2 diabetes, lower HMW adiponectin concentrations are associated with inadequate triglyceride and HDL control; higher TNF-α, with inadequate HDL control, and lower resistin concentrations, with inadequate total cholesterol control.

Predictors of high platelet reactivity during aspirin treatment in patients with type 2 diabetes.

BACKGROUND: Diabetes mellitus type 2 (DM2) is associated with high platelet reactivity both in patients who do not receive antiplatelet drugs and in those treated with acetylsalicylic acid (ASA). The pathomechanism of this phenomenon has not been fully understood. AIM: 1. To evaluate variability of platelet reactivity in patients with DM2 treated with oral antidiabetic drugs and receiving chronic ASA therapy. 2. To identify independent predictors of high platelet reactivity during ASA therapy in patients with DM2. METHODS: We studied 171 patients with DM2 treated with oral antidiabetic drugs and receiving long-term treatment with 75 mg of ASA daily, selected among the participants of the prospective AVOCADO study. Platelet function was simultaneously evaluated using 4 methods: 1. measurement of serum thromboxane B2 (TXB2) concentration; 2. measurement of urinary 11-dehydrothromboxane B2 (11-dhTXB2) concentration; 3. VerifyNow® automated analyser; 4. PFA-100® automated analyser.High platelet reactivity was defined as at least 3 of the following criteria: 1. serum TXB2 concentration in the upper quartile;2. urinary 11-dhTXB2 concentration in the upper quartile; 3. value ≥ 550 aspirin reaction units (ARU) by VerifyNow®;4. collagen-epinephrine closure time (CEPI-CT) below median of readings other than 300 s by PFA-100®. In all patients, DM2 control was evaluated, insulin resistance was measured using HOMA-IR, and routine laboratory tests were performed, including full blood count, renal function parameters, and inflammation markers. RESULTS: Mean patient age was 67.8 years, and median duration of DM2 was 5 years. We found poor agreement between different tests of platelet function. ARU ≥ 550 (VerifyNow®) was found in 14.0% of patients, and CEPI-CT below median of readings other than 300 s (PFA-100®) was found in 32.8% of patients. Our criteria of high platelet reactivity were met by 9.9% of patients. In multivariate logistic regression analysis, independent predictors of high platelet reactivity despite ASA therapy included chronic heart failure, current smoking, and higher leukocyte count. CONCLUSIONS: 1. Patients with DM2 are characterised by large variability of platelet reactivity, with little agreement between various methods. 2. Smoking, chronic heart failure, and subclinical inflammation may be associated with high platelet reactivity in patients with DM2 treated with ASA.

[Assessment of neuropeptide Y, leptin and leptin-receptor concentrations in teenagers suffering from anorexia nervosa]. / Ocena wartosci stezen neuropeptydu Y, leptyny oraz receptora leptyny u nastolatek chorych na anoreksje.

INTRODUCTION: Anorexia nervosa (AN) is the third most common chronic disorder affecting adolescents and is associated with high mortality risk. The predominant symptom of anorexia nervosa is persistent and intentional striving to achieve weight loss initiated and/or sustained by the patient, leading to cachexia. Until now the cause of the condition remains unknown, but seems to be multifactoral. Patients with AN develop multi-organ complications and endocrine disorders affecting multiple disturbances of energy metabolism. Neuropeptide Y and leptin can be found between chemical substances regulating feelings of hunger and satiety. Neuropeptide Y plays the main role in the regulation of energetic homeostasis of the organism, feeding customs, sexual and reproductive functions. Concentration of neuropeptide Y increases during starvation and decreases after feeding. In anorexia nervosa the concentration of neuropeptide Y increases and, by doing that, decreases the excrection of gonadoliberines and gonadotropines. Leptin influences the feeling of hunger and its synthesis takes part, among others, in adiposal tissue. It also influences the menstruation disturbances. Rising leptin concentrations, with accompanying increasing adiposity is known to be the main factor influencing the puberty and the reverse of the malfunction of hypothalamic-pituitary-gonadal axis in malnourished persons. During hunger and low calorie intake, leptin concentration decreases, independently of adiposity. AIM: The main aim of the study was to assess concentrations of neuropeptide Y, leptin and leptin receptor in teenagers treated for anorexia nervosa. MATERIALS AND METHODS: The study was conducted between 2007- 2011 in a group of 45 female teenagers with anorexia nervosa and a control group consisting of 59 healthy regularly menstruating female age peers. Concentrations of leptin, leptin receptor and neuropeptide Y (NPY) have been determined by using immunoenzymatic tests. Blood samples were obtained in fasting state. The Ethics Committee of the Medical University of Lodz approved of the study. RESULTS: There were statistically significant differences between mean values of BMI (14.6 vs. 19.83), median value of leptin concentration (3.79 vs. 12.09), proportions of LEP/BMI (0.1986 vs. 0.5701) in the study group when compared to controls. Higher values were found in the study group if compared to the percentage of body mass insufficiency--(23.09 vs. 3.97), neuropeptide Y concentration--(0.33 vs. 0.19), proportions of NPY/BMI--(0.023 vs. 0.0095), concentration of leptin receptor--(30.25 vs. 19.45), proportions of LR/BMI--(2.1048 vs. 0.9744). CONCLUSIONS: Low concentrations of leptine correlate to high concentrations of leptin receptor. A positive correlation between low body mass index and leptin receptor concentration and proportions of LR to BMI was found. A negative correlation was found between body mass loss and leptin concentration. The increasing concentration of neuropeptide Y, correlated to body mass deficency with existing high concentrations of leptin, could suggest disturbances of their regulatory axis.

Effect of ASA dose doubling versus switching to clopidogrel on plasma inflammatory markers concentration in patients with type 2 diabetes and high platelet reactivity: the AVOCADO study.

BACKGROUND: The aim of the study was to compare the effects of 2 strategies of antiplatelet treatment (i.e., 150 mg ASA vs. 75 mg clpoidogrel) on plasma level of inflammatory markers in type 2 diabetes mellitus (T2DM) patients with high platelet reactivity (HPR). METHODS: Study cohort consisted of 304 T2DM patients on chronic ASA therapy (75 mg per day) participating in the Aspirin Versus/Or Clopidogrel in Aspirin-resistant Diabetics inflammation Outcomes (AVOCADO) study. Patients with HPR defined as Platelet Function Analyzer (PFA)-100 collagene/epinephrine closure time (CEPI-CT) < 193 s (n = 80) were randomized to 150 mg of ASA or 75 mg of clopidogrel in 2:3 ratio, respectively. Concentrations of the selected inflammatory markers, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, solubleCD40 ligand (sCD40L), and high sensitivity C-reactive protein (hsCRP), were measured and compared in both treatment groups before and after 8 weeks of treatment in both groups. RESULTS: Out of 234 patients included into final analysis, the total of 34.2% (n = 80) patients displayed HPR, of which 14.1% (n = 33) were randomized into 150 mg of ASA group and 20.1% (n = 47) into 75 mg of clopidogrel group. Treatment with clopidogrel was a positive predictor (stepwise multiple regression analysis) of reduction of sCD40L concentration (odds ratio [OR] 4.15; p = 0.013), while treatment with 150 mg ASA was a positive predictor of reduction of IL-6 concentration (OR 4.38; p = 0.033). There was no statistically significant differences between clopidogrel and ASA 150 mg treatment in respect to predictive value for decreased hsCRP concentrations or increased TNF-α concentrations. CONCLUSIONS: Increasing the dose of ASA from 75 mg to 150 mg daily or switching ASA 75 mg to clopidogrel 75 mg daily may reduce concentrations of some inflammatory markers (in particular hsCRP, IL-6 and CD40L) in T2DM patients with HPR treated previously with 75 mg of ASA.

Insulin-like factor 3 -- a new hormone related to polycystic ovary syndrome?

INTRODUCTION: The aim of this study was to find a correlation between insulin-like factor 3 (INSL3) and androgens: androstenedione (A), free testosterone (fT), and total testosterone (T), in two groups of polycystic ovary syndrome (PCOS) women: those with a body mass index (BMI) lower than 25 kg/m(2) and those with a BMI higher than 25 kg/m(2). The association between INSL3 and other serum parameters: luteinising hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulphate (DHEA-S), sex hormone binding globulin (SHBG) and glucose and insulin were also investigated. MATERIAL AND METHODS: The study group comprised 37 PCOS women aged 27 ± 4 years. The control group consisted of 34 healthy, premenopausal women (aged 24.2 ± 1.2) with regular menses and no signs of hyperandrogenism. There were 27 PCOS women of normal weight (BMI < 25 kg/m(2)), and ten overweight individuals (BMI ≥ 25-30 kg/m(2)). Correlations between level of INSL3 and LH, FSH, T, fT, A, DHEA-S, SHBG, metabolic tests, height, weight, and WHR (waist-to-hip ratio) were also investigated. RESULTS: PCOS women showed non-significantly higher levels of INSL3 compared to the healthy controls (64.6 ± 27.7 and 62.7 ± 20.0 ng/mL, respectively). However, we identified very strong correlations between INSL3 and androstenedione (r = 0.48, p = 0.0115), and free (r = 0.44, p = 0.0108) and total testosterone (r = 0.46, p = 0.0057) in the PCOS subgroup with a BMI of < 25 kg/m(2). There was no statistically significant correlation between INSL3 and LH in any subject of the PCOS group, nor between INSL3 and FSH, DHEA-S, glucose, basal insulin concentration or HOMA-IR. CONCLUSIONS: We found a positive correlation between INSL3 and androgens in PCOS women, especially those with a BMI of < 25 kg/m(2). This may play a key role in PCOS pathophysiology.

Do statins influence platelet reactivity on acetylsalicylic acid therapy in patients with type 2 diabetes?

BACKGROUND: Type 2 diabetes (T2DM) patients are at increased risk of cardiovascular events despite long-term acetylsalicylic acid (ASA) therapy. This study was performed to establish the prevalence of high platelet reactivity (HPR) on ASA in T2DM and to identify its predictors. METHODS: The study included 185 T2DM on chronic ASA therapy and to assess platelet reactivity during long-term ASA therapy, we applied the point-of-care method VerifyNow(®) aspirin test (Accumetrics, San Diego, CA, USA). RESULTS: Compared with the low platelet reactivity (LPR) group, patients with HPR had higher triglyceride levels (145 vs. 118 mg/dL, p = 0.041), were less frequently treated with statins (57.1% vs. 75.3%; p = 0.038) and tumor necrosis factor-alpha (TNF-α) concentrations were higher (2.15 vs. 1.74 pg/mL; p = 0.052). In a multivariate analysis only statin therapy (OR 0.375; 95% CI 0.15-0.91; P = 0.030) and lower concentrations of TNF-α (for each 1.0 pg/ml: or 1.3; 95% ci 1.00-1.72; p = 0.046) were predictive of LPR. CONCLUSIONS: Our study provides indirect evidence that the beneficial effect of statins on platelet activity may be related to their non-lipid-mediated, pleiotropic mechanisms of action. This might have been partly related to decreased platelet reactivity in patients receiving statin therapy. In our study in patients with T2DM, platelet reactivity on ASA therapy measured with VerifyNow(®) was associated with TNF-α concentrations and statin therapy. These results may imply a role for subclinical systemic inflammation and a beneficial effect of statins in the development of HPR in T2DM.

Measuring salivary androgens as a useful tool in the diagnosis of polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the commonest endocrinopathies. Clinically it can present as oligo-/amenorrhoea, hyperandrogenism and/or fertility problems. MATERIAL AND METHODS: The study involved 60 women admitted to the Department of Internal Medicine and Endocrinology at the Medical University of Warsaw. The initial evaluation, including case history and two-dimensional vaginal ultrasound, was performed by gynaecologists. All hormonal investigations (fT, free testosterone; bioT, bioavailable testosterone; T, total testosterone; T EQ, free testosterone by equilibrium dialysis; A, androstenedione; A EQ, free androstenedione by equilibrium dialysis; salA, salivary androstenedione; salT, salivary testosterone) were performed. Anthropometrical data, excess facial and body hair, acne, and menstrual cycle frequency were also assessed. RESULTS: Increased levels of T, fT, T EQ and A were noted in 20.0%, 89.8%, 100% and 28.3% of women, respectively. A very high correlation was found between salivary androstenedione and free androstenedione estimated by EQ in plasma (p < 0.05, r = 0.67), and total androstenedione in plasma (p < 0.05, r = 0.71). Correlation between salT and T was r = 0.31, p < 0.05 and salT and T EQ was r = 0.26, p = 0.04. Correlation between salA/salT and T, A in plasma (respective values r = 0.39 and r = 0.28, p < 0.01) and between salA/salT and A EQ, T EQ (respectively r = 0.34 and r = 0.48, p < 0.01) was evident. CONCLUSIONS: SalA/salT ratio may be a good indicator of hyperandrogenism in women. We also confirm that measurement of androstenedione in plasma may be useful in making a diagnosis of PCOS.

Iodine status of pregnant women from central Poland ten years after introduction of iodine prophylaxis programme.

INTRODUCTION: Until 1997, Poland was one of the European countries suffering from mild/moderate iodine deficiency. In 1997, a national iodine prophylaxis programme was implemented based on mandatory iodisation of household salt with 30 ± 10 mg KI/kg salt, obligatory iodisation of neonatal formula with 10 µg KI/100 mL and voluntary supplementation of pregnant and breast-feeding women with additional 100-150 µg of iodine. Our aim in this study was to evaluate the iodine status of pregnant women ten years after iodine prophylaxis was introduced. MATERIAL AND METHODS: A cross-sectional study was undertaken in 100 healthy pregnant women between the fifth and the 38th week of gestation with normal thyroid function, singleton pregnancy, normal course of gestation, without drugs known to influence thyroid function except iodine. Serum TSH, fT(4), fT(3), thyroglobulin (TG), anti-peroxidase antibodies (TPO-Ab), anti-thyroglobulin antibodies (TGAb) and urinary iodine concentration (UIC) were determined. Thyroid volume and structure were evaluated by ultrasonography. RESULTS: Fifty nine per cent of studied pregnant women had a diet rich with iodine carriers and 35% obtained iodine supplements. Twenty eight per cent appeared to have a goitre: 11 diffuse and 17 a nodular one, median goitre volume was 18.7 mL (range 6.8-29.0 mL). Median UIC was 112.6 µg/L (range 36.3-290.3 µg/L), only 28% of women had UIC ≥ 150 µg/L. Median UIC was significantly higher in the group receiving iodine supplements than in the group without iodine supplements: 146.9 µg/L v. 97.3 µg/L respectively, p 〈 0.001. Serum TSH, fT(3) and fT(3)/fT(4) molar ratio increased significantly during pregnancy while fT(4) declined. Median serum TG was normal: 18.3 ng/mL (range 0.4-300.0 ng/mL) and did not differ between trimesters. Neonatal TSH performed on the third day of life as a neonatal screening test for hypothyroidism was normal in each case: median value was 1.49 mIU/L (range 0.01-7.2 mIU/L). Less than 3% (2 out of 68) of results were 〉 5 mIU/L. CONCLUSION: Iodine supplements with 150 µg of iodine should be prescribed for each healthy pregnant woman according to the assumptions of Polish iodine prophylaxis programme to obtain adequate iodine supply. (Pol J Endocrinol 2010; 61 (6): 646-651).

[Diagnostic usefulness of selected tumor markers (CA125, CEA, CYFRA 21-1) in bronchoalveolar lavage fluid in patients with non-small cell lung cancer]. / Przydatnosc oznaczania wybranych markerów nowotworowych (CA125, CEA, CYFRA 21-1) w plynie z plukania oskrzelowo-pecherzykowego w diagnostyce chorych z niedrobnokomórkowym rakiem pluca.

Numerous studies have been performed to determine diagnostic or prognostic utility of tumor markers in patients with lung cancer. The aim of the study was to evaluate the diagnostic usefulness of the tumor markers CA 125, CEA and CYFRA 21-1 in bronchoalveolar lavage fluid (BALF) in patients with non-small cell lung cancer (NSCLC). BAL was performed in 13 patients with NSCLC during diagnostic bronchofibroscopy. The control group consisted of 12 patients with sarcoidosis and 13 healthy volunteers. Tumor markers were determined in BALF supernatants using electrochemiluminescence technique (Elecsys 1010, Roche). To determine optimal cut-off values of tumor markers in BALF ROC curve was used. CEA and CA 125 concentration in BALF were significantly higher in NSCLC patients than in healthy volunteers and patients with sarcoidosis. CYFRA 21-1 in BALF was higher in NSCLC patients than in healthy volunteers, but no significant difference was found between NSCLC and sarcoidosis patients. The cut-off values of BALF concentration of CA 125, CEA and CYFRA 21-1 were 95 IU/mL, 3 ng/ml and 3 ng/ml, respectively. The sensitivity and specificity of CEA and CA 125 in BALF were 100%, 84% and 92%, 80%, respectively. In conclusion, we suggest that among the chosen markers, determination of CEA in BALF is the most useful in diagnosis of NSCLC. It may be a complementary method in diagnosing of patients in whom tumor cannot be visualized by bronchofibroscopy. These results need confirmation in larger groups of patients.