Search

Funding Acknowledgements Type of funding sources: None. Introduction Since mitral regurgitation (MR) is a very common finding in patients with hypertrophic cardiomyopathy (HCM), the evaluation of the mitral valve anatomy and the degree of MR is of utmost importance in this population. However, data regarding the prognostic value of different degrees of MR in HCM remains scarce. Purpose The aim of this study was to determine whether the presence of a higher degree of MR affects: 1) long term prognosis; 2) clinical and echocardiographic presentation of HCM patients. Material and Methods We included prospectively 102 patients, diagnosed with primary asymmetric HCM. The degree of MR was determined echocardiographicaly according to current recommendations of the American Association of Echocardiography. According to the MR severity, patients were divided into 2 groups: Group 1 (n = 52) with no/trace or mild MR and Group 2 with moderate or moderate to severe MR. All patients had clinical and echocardiographic examination, 24-hour Holter ECG and NT pro BNP analysis performed. The primary outcome was a composite of: 1) HCM related death or sudden death; 2) hospitalization due to acute heart failure; 3) sustained ventricular tachycardia; 4) ischemic stroke. Results Patients with higher MR degree had more frequent chest pain (p = 0.039), syncope (p = 0.041) and NYHA II functional class (p 10), as well as higher levels of NT pro BNP (p = 0.001). By Kaplan-Meier analysis we demonstrated that the event free survival rate during follow up of median 75 (IQR 48-103) months was significantly higher in Group 1 compared to the Group 2 (79% vs. 46%, p Conclusion Presence of moderate, or moderate to severe MR was associated with poor long-term outcome of HCM patients. These results indicate the importance of an adequate MR assessment and detailed evaluation of the mitral valve anatomy in the prediction of complications and adequate treatment of patients with HCM. Abstract Figure.

BACKGROUND/AIMS The most effective and safe treatment protocol for Graves' orbitopathy (GO) needs to be further assessed. The aim of the present study was to evaluate the efficacy, safety and outcome of parenteral versus parenteral and oral glucocorticoid (GC) protocols in euthyroid patients with untreated and active moderate to severe GO. METHODS This was a retrospective observational study in 140 patients comparing intravenous GC pulses only (IVGC group, 74 patients, 51 ± 11 years) with historical controls of combined oral and intravenous GC therapy (CombGC group, 66 patients, 49 ± 10 years, P = ns). IVGC therapy included infusions of 500 mg of methylprednisolone weekly for the first six weeks, followed by infusions of 250 mg weekly for the remaining six weeks (cumulative dose 4.5 g). CombGC therapy included 500 mg of methylprednisolone in 500 mL of saline solution for two alternative days, followed by oral prednisone tapering dose repeated each month for the next 5 months (cumulative dose 10.2 g). RESULTS The overall success of the treatment was 43/66 (65%) in the CombGC group and 37/73 (51%, P = .071) in the IVGC group. Deterioration of GO developed in four (6%) patients during CombGC therapy and in nine (12%, P = .214) patients during IVGC therapy. After 6 months, relapse of GO was observed in 10/37 (26%) in the IVGC group, whereas none of the patients in CombGC had a relapse (P < .001). There were significantly more side effects in the CombGC versus IVGC group (49/66, 74% vs 28/74, 38%, P < .001). CONCLUSIONS Our data suggest that CombGC therapy was more efficient with significantly less relapse rate, but with more side effects in comparison to IVGC therapy.

Background Percutaneous coronary intervention of chronic total coronary occlusion (PCI of CTO) is proved to reduce symptoms of angina and long term survival. Purpose This study aimed to assess systolic and diastolic left ventricular function with standard echocardiographic indices. Methods We analyzed total of 46 CTO patients (age 58 ± 9, 73% male). Measures were obtained with the transducer in the apical four-chamber view. Doppler time intervals were measured from mitral inflow and left ventricular outflow Doppler tracings by pulsed wave Doppler. The isovolumetric relaxation time (IVRT) was measured from closure of the aortic valve to opening of the mitral valve. The isovolumetric contraction time (IVCT) was measured from closure of the mitral valve to opening of the aortic valve. Ejection time (ET) was measured from the opening to the closure of the aortic valve on the LV outflow velocity profile. Myocardial performance index (MPI) is simple method for evaluation of overall cardiac function and is independent of heart rate and blood pressure. MPI was equal to the sum of the IVRT and IVCT divided by the ET. Velocity of early mitral filling wave (E) was measured and divided by average peak early diastolic annular velocity (e") which was measured as average value between septal and lateral side of the mitral annulus using Doppler tissue imaging. The E/e’ ratio was calculated to estimate the LV filling pressures Results Six months after PCI of CTO patients showed no change in ejection fraction (EF) (55.69 ± 8.56% vs. 54.83 ± 8.44%, p = 0.10). MPI was significantly decreased (0.676 ± 0.99 vs. 0.632 ± 0.96 p Conclusion PCI of CTO improves overall cardiac function, particularly diastolic function in patients with reduced ejection fraction.

Background Percutaneous coronary intervention for chronic total occlusion (PCI CTO) is still high risk procedure and it is doubtful will it become standard of care. There is evidence that it can reduce angina but even silent ischemia represent ischemic burden that ultimately lead to left ventricle remodeling and electrical instability. Purpose Our aim was to access effectiveness of percutaneous coronary intervention (PCI) when added to optimal medical therapy (OMT) on myocardial function. Methods We compared two groups of pts. First patients with percutaneous coronary intervention of chronic total occlusion with optimal medical therapy and second group - patients with only optimal medical therapy (control group). Echocardiographic exam was performed before randomization and after 6 months of follow-up. Doppler intervals- isovolumetric relaxation time (IVRT), isovolumetric contraction time (IVCT) and ejection time (ET) were measured. MPI (Myocardial performance index) is equal to the sum of the IVRT and IVCT divided by the ET. Velocity of early mitral wave (E) was divided by average peak early diastolic annular velocity (e"). Peak longitudinal strain was assessed in 17 left ventricular segments. Time intervals from start Q/R on electrocardiogram to peak negative strain during the cardiac cycle were assessed. Mechanical dispersion was defined as the standard deviation of this time intervals from 17 segments, reflecting myocardial contraction heterogeneity. Results A total of 94 age matched CTO patients (48 in PCI + OMT group and 46 in OMT) were analyzed. Changes in ejection fraction (EF), diastolic function represented by E/e", global cardiac function represented by MPI, global longitudinal strain (GLS) and myocardial dispersion changes were compared between groups. At follow up between groups in there was no significant change in ejection fraction (EF), diastolic function, GLS and mechanical dispersion, but there was improvement in MPI. Conclusion Myocardial performance index is sensitive marker which can detect subtle improvement in global myocardial function after recanalization of chronic total occlusion.. Variable PCI + OMT (n = 46) OMT (n = 48) ΔOMT vs. ΔPCI + OMT p value baseline At 6month follow up P value baseline At 6month follow up P value EF (%) 55.69 ± 8.56 54.83 ± 8.44 0.10 50.22 ± 11.71 51.42 ± 10.45 0.06 0.71 MPI 0.676 ± 0.99 0.632 ± 0.96

Background Heart rate recovery (HRR) has been shown to predict cardiovascular and all-cause morbidity and mortality in different populations. Recent studies have indicated the CHA2DS2-VASc score can be used as predictor of mortality in patients with coronary artery disease, without atrial fibrillation. However, the relation between these two parameters has not yet been documented. The Aim: The aim of this study was to determine the relation between CHA2DS2-VASc score and impaired heart rate recovery in patients without inducible myocardial ischemia. Methods Our study comprised of 2699 consecutive patients (1319 male, 42.8%, average age 60 ± 11 years) who underwent treadmill exercise testing (stress echocardiography or stress echocardiography) according to Bruce protocol for the assessment of myocardial ischemia. We excluded patients with the systolic heart failure (left ventricle ejection fraction Results Out of 2699 patients, 378 (12.3%) had a positive test and they were excluded from further analysis. Of the remaining 2321 patients, 251 (10.8%) had an impaired HRR, whereas 2070 (89.2%) had normal HRR. Previously known coronary artery disease (previous myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft surgery) had 78 (3.4%) patients. Patients with impaired HRR had significantly higher CHA2DS2-VASc score (3.1 ± 1.3 vs 2.3 ± 1.2, p Conclusion CHA2DS2-VASc score is an independent predictor of impaired HRR in patients without inducible ischemia.

To evaluate the hypothesis that breast arterial calcification (BAC) may predict coronary artery disease (CAD) severity.The study comprised 102 women45 years (mean age 62±8 years) referred for digital mammography after coronary angiography. BAC was assessed using the Likert scale and CAD severity was assessed using the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery trial) score.In comparison to the low SYNTAX score group (≤22) patients with a intermediate-to-high SYNTAX score (22) were older (p=0.001), they more often had hypercholesterolaemia (p0.001), diabetes (p=0.021), and a history of smoking (p=0.048). They also had a statistically higher level of fasting blood glucose (p0.001), glycated haemoglobin (HbA1C; p0.001), triglycerides (p=0.002), fibrinogen (p=0.001), whereas high-density lipoprotein (HDLc) was lower than in the group with a SYNTAX score ≤22 (p=0.005). BAC was significantly higher in patients with a SYNTAX score22 (p0.001). At multivariate analysis, BAC (odds ratio [OR] 34.24, 95% confidence interval [CI]: 8.05-145.7, p0.001), hypercholesterolaemia (OR 22.65, 95% CI: 4.18-122.81, p0.001) and fibrinogen (OR 2.55, 95% CI: 1.28-5.07, p=0.008) were independent predictive factors for patients with intermediate-to-high SYNTAX score.In women45 years, there was a significant correlation between the severity of CAD as evaluated by the SYNTAX score and BAC as evaluated by the Likert scale. BAC, hypercholesterolaemia, and fibrinogen may be used as an additional diagnostic tool to predict the presence and severity of CAD.

The increased secretion of thyroid gland hormones affects the cardiovascular system by increasing heart rate and often by increasing systolic and diastolic blood pressure. We examined the influence of elevated thyroid hormone on blood pressure. Blood pressure monitoring was performed prior to the introduction of therapy in people with increased FT4 and on therapy when FT4 was in the normal range. We analyzed 32 people, of which 26 women had normal blood pressure values measured by blood pressure monitoring. Average age 45 and body mass index 27 kg/m2. Blood pressure was measured by monitoring blood pressure for 24 hours. On average, before the introduction of the therapy, it was 133/83 mmHg P 96 / min. The blood pressure on average on therapy with tireosuppressive was 128/82 mmHg P 74 / min. The Wilcoxon-Mann-Whitney paired test shows a significant P

Introduction. In interpreting thyroid hormones results it is preferable to think of interference and changes in concentration of their carrier proteins. Outline of Cases. We present two patients with discrepancy between the results of thyroid function tests and clinical status. The first case presents a 62-year-old patient with a nodular goiter and Hashimoto thyroiditis. Thyroid function test showed low thyroid-stimulating hormone (TSH) and normal to low fT4. By determining thyroid status (ТSH, T4, fT4, T3, fT3) in two laboratories, basal and after dilution, as well as thyroxine-binding globulin (TBG), it was concluded that the thyroid hormone levels were normal. The results were influenced by heterophile antibodies leading to a false lower TSH level and suspected secondary hypothyroidism. The second case, a 40-year-old patient, was examined and followed because of the variable size thyroid nodule and initially borderline elevated TSH, after which thyroid status showed low level of total thyroid hormones and normal TSH. Based on additional analysis it was concluded that low T4 and T3 were a result of low TBG. It is a hereditary genetic disorder with no clinical significance. Conclusion. Erroneous diagnosis of thyroid disorders and potentially harmful treatment could be avoided by proving the interference or TBG deficiency whenever there is a discrepancy between the thyroid function results and the clinical picture.

Introduction: The most common cause for persistent elevation of TSH levels in hypothyroid patients treated with levothyroxine is poor compliance. The Levothyroxine Absorption Test (LAT) is usually confirmed this phenomenon called 'pseudo-malabsorption'. Case report: 60-year-old female, weight 60kg, BMI 24.3kg/m2, presented with sleepiness, tiredness, fatigue and forgetfulness. Her skin was very dry and flaky. She had low tolerance of effort, poor appetite with weight oscillation around 2kg, constipation and sometimes heartburn. Hypothyroid for ten years after radioiodine treatment of Graves' disease. Her TSH levels were higher than normal, TSH 20-70mIU/L, in spite of efforts to adjust the dose (different LT4 preparations). In last two years her daily LT4 dose was 900 (15 µg/kg), 3x300mcg, 500+400mcg. Comorbidities: depression, angina, hypertension, absolutely arrhythmias (with inadequate INR in last two months). Before testing TSH 33.6mIU/L, FT4 4.25 pmol/L. Standard (1000 µg) LAT was performed under supervision. TSH, T4 and FT4 were measured 2h, 4h, 6h and 24h upon LT4 administration. Baseline values were TSH 26.92 mIU/L; FT4 4.4pmol/L; T4 41.5pmol/L. The lack of TSH fall with slight T4 and FT4 increase, significantly below expected AUC, pointed an inadequate absorption. It was started with 300 µg LT4 oral suspension, after testing. The presence of fat in the stool and positive antiparietal antibodies increased suspicion to malabsorptiv syndrome. EGDS was performed, PH finding confirmed H. pylori positive chronic atrophic gastritis, without morphological elements for GSE. Eradication treatment and IPP were introduced. After four weeks her thyroid hormones were TSH 1.63 mIU/L; FT4 26.6pmol/L, FT3 3.87pmol/L. Conclusion: LAT is useful for identifying much rare malabsorption. The adequate treatment lead to proper substitution and avoidance of no rationale increase of levothyroxine dose.

UVOD: Nefrolitijaza se sve vise smatra sistemskom bolescu koja je udružena sa hronicnom bubrežnom insuficijencijom i kostanim poremecajima. Ako se ne leci to je hronicna bolest sa stopom ponavljanja vise od 50% za 10 godina. Pacijenti sa cistinurijom imaju visoku stopu rekurentne kalkuloze. PRIKAZ SLUCAJA: Tridesetsedmogodisnja pacijentkinja žalila se na bolove u levoj slabini sa sirenjem prema napred pri naglom ustajanju prilikom ispitivanja zbog rekurentne kalkuloze. U 24. godini ustanovljena je kalkuloza desnog bubrega i zbog hidronefroze i anurije urađena je nefrektomija. Poslednje tri godine, bar jednom godisnje, imala je anuriju a litoklast kalkulusa u pelvicnom delu levog bubrega rađenje 2009. i 2011.g. U maju 2009. prvi put je pregledana od strane nadležnog endokrinologa kada je PTH bio blago povisen 70,8 (15-65ng/l), uz uredan jonizovani kalcijum u serumu. Kvantitativne analize 24h urina pokazale su uredne vrednosti kreatinin klirensa, proteinurije, natriureze, kaliureze, normalne vrednosti kalciurije, fosfaturije, oksalurije, urikozurije i citraturije. U hormonskim analizama granican PTH 66 (10-65ng/L) i deficit vitamina D (15,3ng/L). Analiza hemijskog sastava kalkulusa ukazala je da se radi o cistinskim kalkulusima. Testiranjem sina i same pacijentkinje u Institutu za zdravstvenu zastitu majke i deteta 'dr Vukan Cupic', na osnovu povecanog izlucivanja cistina, lizina, ornitina i arginina u 24h urinu, kod pacijentkinje je potvrđena cistinurija. Savetovanaje prevencija formiranja kalkulusa (povecan unos tecnosti na 4-4,5l/d, alkalizacija urina tabletama kalijum-citrata, uz monitoring pH urina test trakama i kontrolu kalemije) uz terapiju Vigantol kapima zbog hipovitaminoze D. ZAKLJUCAK: Prevencija kalkuloze je moguca nakon pravilno postavljene dijagnoze. Zato je važno da se utvrdi uzrok nefrolitijaze.

Objective To construct a predictive score for the development or progression of Graves’ orbitopathy (GO) in Graves’ hyperthyroidism (GH). Design Prospective observational study in patients with newly diagnosed GH, treated with antithyroid drugs (ATD) for 18 months at ten participating centers from EUGOGO in 8 European countries. Methods 348 patients were included with untreated GH but without obvious GO. Mixed effects logistic regression was used to determine the best predictors. A predictive score (called PREDIGO) was constructed. Results GO occurred in 15% (mild in 13% and moderate to severe in 2%), predominantly at 6–12 months after start of ATD. Independent baseline determinants for the development of GO were clinical activity score (assigned 5 points if score > 0), TSH-binding inhibitory immunoglobulins (2 points if TBII 2–10 U/L, 5 points if TBII > 10 U/L), duration of hyperthyroid symptoms (1 point if 1–4 months, 3 points if >4 months) and smoking (2 points if current smoker). Based on the odds ratio of each of these four determinants, a quantitative predictive score (called PREDIGO) was constructed ranging from 0 to 15 with higher scores denoting higher risk; positive and negative predictive values were 0.28 (95% CI 0.20–0.37) and 0.91 (95% CI 0.87–0.94) respectively. Conclusions In patients without GO at diagnosis, 15% will develop GO (13% mild, 2% moderate to severe) during subsequent treatment with ATD for 18 months. A predictive score called PREDIGO composed of four baseline determinants was better in predicting those patients who will not develop obvious GO than who will.

Assessment of insulin sensitivity based on a single measurement of insulin and glucose, is both easy to understand and simple to perform. The tests most often used are HOMA and QUICKI. The aim of this study was to assess the biological variability of estimates of insulin sensitivity using HOMA and QUICKI indices. After a 12-h fast, blood was sampled for insulin and glucose determination. Sampling lasted for 90 min with an intersample interval of 2 min. A total of 56 subjects were included in the study, and in nine subjects sampling was done before and after weight reduction, so total number of analyzed series was 65. To compute the reference value of the insulin sensitivity index, averages of all 46 insulin and glucose samples were used. We also computed point estimates (single value estimates) of the insulin sensitivity index based on the different number of insulin/glucose samples (1-45 consecutive samples). To compute the variability of point estimates a bootstrapping procedure was used using 1000 resamples for each series and for each number of samples used to average insulin and glucose. Using a single insulin/glucose sample HOMA variability was 26.18 ± 4.31%, and QUICKI variability was 3.30 ± 0.54%. For 10 samples variability was 11.99 ± 2.22% and 1.62 ± 0.31% respectively. Biological variability of insulin sensitivity indices is significant, and it can be reduced by increasing the number of samples. Oscillations of insulin concentration in plasma are the major cause of variability of insulin sensitivity indices.

Tirotoksicna periodicna paraliza je retko oboljenje, obicno se tesko dijagnostikuje, a ima veliki znacaj pre svega zbog potencijalnih teskih komplikacija. Najcesca je u Aziji, sa incidencom 1.8-1.9% pacijenata sa tirotoksikozom, dok je incidenca u ostalim geografskim regijama znacajno manja. Predominantno se javlja kod muskaraca mlađe životne dobi, manifestuje se recidivirajucim epizodama misicne slabosti od blage do kompletne flakcidne paralize, trajanja do 72 sata, sa potpunom rezolucijom između ataka. Najcesce je zahvacena proksimalna muskulatura donjih ekstremiteta, ali može se ispoljiti i kao tetrapareza, bez poremecaja senzibiliteta i funkcije sfinktera. Težina paralitickog ataka korelira sa težinom hipokalijemije, ali ne i sa klinickim manifestacijama tirotoksikoze ili nivoom tiroidnih hormona. Najozbiljnije komplikacije su paraliza respiratorne muskulature i teske kardijalne aritmije. TPP je najcesca u obolelih od M. Graves, a moguca je i u slucajevima subakutnog tiroiditisa, toksicne nodozne strume, toksicnog adenoma, TSH sekretujuceg tumora hipofize i jatrogene hipertireoze. Kljucni događaj paralitickog ataka je hipokalijemija (

The aim of the study was to evaluate thyroid-stimulating hormone (TSH) concentration in a reference group and to compare it with the TSH in subjects with high probability of thyroid dysfunction. The study population consisted of 852 subjects. The reference group consisting of 316 subjects was obtained by the exclusion of the subjects having thyroid disease, taking thyroid influencing drugs, having increased thyroid peroxidase (TPO) antibodies, or having abnormal thyroid ultrasound. 42 high probability of thyroid dysfunction subjects were defined by the association of increased TPO antibody concentration, changed echogenicity, and changed echosonographic structure of thyroid parenchyma. In the reference group TSH reference range was 0.45 mU/l (95% CI 0.39-0.56 mU/l) to 3.43 mU/l (95% CI 3.10-4.22 mU/l). To distinguish reference and high probability of thyroid dysfunction group a TSH threshold was calculated. At a threshold value of 3.09 mU/l (95% CI 2.93-3.38 mU/l), specificity was 95% and sensitivity 38.1%. Using 2 different approaches to find upper limit of the TSH reference range we obtained similar results. Using reference group only a value of 3.43 mU/l was obtained. Using both reference group and subjects with the high probability of thyroid dysfunction we obtained 95% CI for the upper reference limit between 2.93 and 3.38 mU/l. Based on these premises, it could be argued that conservative estimate of the TSH upper reference range should be 3.4 mU/l for both sexes.

ObjectiveInterleukin 6 (IL6) has the ability to influence each level of the hypothalamo-pituitary–adrenocortical (HPA) axis. The aim of the study was to test whether IL6 concentration correlates with the adrenal cortex response to ACTH in healthy humans. We postulated that higher basal IL6 concentration would be associated with the higher cortisol response to the stimulation.Design and methodsBasal IL6 concentration was measured and a low dose (1 μg) ACTH test was performed to assess cortisol response. Twenty-seven apparently healthy subjects (11 male, 16 female, mean age 31.1 years, age range 22–47 years) were included in the study.ResultsData are presented as mean±s.e.m. Basal IL6 level was 0.84±0.10 pg/ml. Basal cortisol was 351.9±18.3 nmol/l. Maximal cortisol during synacthen test was 653.0±20.6 nmol/l. Maximal cortisol increment was 301.1±20.0 nmol/l. IL6 concentration was not correlated with basal or maximal cortisol concentration, but correlated significantly with cortisol increment (r=0.63, 95% confidence interval) 0.42–0.83).ConclusionsIn our study, we found that higher basal IL6 concentration is associated with the higher cortisol response to ACTH stimulation. Based on previous research and our data, IL6, even in low concentrations and under physiologic conditions, modulates adrenal cortex responsivity to ACTH. Therefore, it seems that immune modulation of HPA axis is also present under physiologic and not only pathologic conditions.

Introduction: Diagnosis and differential diagnosis of Cushing?s syndrome (CS) remain considerable challenge in endocrinology. For more than 20 years, CRH has been widely used as differential diagnostic test. Following the CRH administration, the majority of patients with ACTH secreting pituitary adenoma show a significant rise of plasma cortisol and ACTH, whereas those with ectopic ACTH secretion characteristically do not. Objective The aim of our study was to assess the value of CRF test for differential diagnosis of CS using the ROC (receiver operating characteristic) curve method. Method A total of 30 patients with CS verified by pathological examination and postoperative testing were evaluated. CRH test was performed within diagnostic procedures. ACTH secreting pituitary adenoma was found in 18, ectopic ACTH secretion in 3 and cortisol secreting adrenal adenoma in 9 of all patients with CS. Cortisol and ACTH were determined -15, 0, 15, 30, 45, 60, 90 and 120 min. after i.v. administration of 100?g of ovine CRH. Cortisol and ACTH were determined by commercial RIA. Statistical data processing was done by ROC curve analysis. Due to small number, the patients with ectopic ACTH secretion were excluded from test evaluation by ROC curve method. Results In evaluated subgroups, basal cortisol was (1147.3?464.3 vs. 1589.8?296.3 vs. 839.2?405.6 nmol/L); maximal stimulated cortisol (1680.3?735.5 vs. 1749.0?386.6 vs. 906.1?335.0 nmol/L); and maximal increase as a percent of basal cortisol (49.1?36.9 vs. 9.0?7.6 vs. 16.7?37.3 %). Consequently, basal ACTH was (100.9 ?85.0 vs. 138.0?123.7 vs. 4.8?4.3 pg/mL) and maximal stimulated ACTH (203.8 ?160.1 vs. 288.0?189.5 vs. 7.4?9.2 pg/mL). For cortisol, determination area under ROC curve was 0.815?0.083 (CI 95% 0.652-0.978). For cortisol increase cut-off level of 20%, test sensitivity was 83%, with specificity of 78%. For ACTH, determination area under ROC curve was 0.637?0.142 (CI 95% 0.359-0.916). For ACTH increase cut-off level of 30%, test sensitivity was 70%, with specificity of 57%. Conclusion Determination of cortisol and ACTH levels in CRH test remains reliable tool in differential diagnosis of Cushing?s syndrome.

Diagnosis and differential diagnosis of Cushing's syndrome remains a challenge in clinical endocrinology. The aim of this study was to establish the value of assessing adrenocorticotropic hormone (ACTH) levels in differential diagnosis of hypercorticism using receiver operating characteristic (ROC) curve. We have evaluated 114 patients with Cushing's syndrome testing the value of pathohistological examination and postoperative testing. The control group consisted of 53 obese healthy persons. ACTH level was determined using a commercial RIA (CIS, France). ACTH secreting pituitary adenoma was found in 56.14% examinees, ectopic secretion in 6.14%, cortisol secreting adrenal adenoma in 37.57%, and adrenal carcinoma in 6.14% of all patients with Cushing's syndrome. Basal ACTH level for pituitary adenoma was 107.29 +/- 75.69 pg/mL; for ectopic secretion 181.63 +/- 149.84 pg/mL; for adrenal adenoma 4.22 +/- 2.32 pg/mL; for adrenal carcinoma 5.50 +/- 7.72 pg/mL; and 34.76 = 10.07 pg/mL in control group. Testing the value of assessing ACTH the area under ROC curve was 0.9965 +/- 0.0071. Test sensitivity was 99.89% and test specificity was 97%. For ACTH cut-off level of 8 pg/mL, test sensitivity was 88.50%, with specificity of 99%. For ACTH cut-off level of 22 pg/mL, test sensitivity was 99.30%, with specificity of 98%. Our intermediate zone from 8 to 22 pg/mL confirms that assessment of ACTH level is a reliable tool in differential diagnosis of Cushing's syndrome.

The prognostic meaning of myocardial viability is most important in patients with severe left ventricular dysfunction and ischaemic heart disease, but its prognostic significance in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction is uncertain. The aim of this study was to assess the prognostic value of a 201 Tl single photon emission computed tomography (SPECT) rest-redistribution study in patients with previous myocardial infarction, ischaemic heart disease and mild-to-moderate myocardial dysfunction. Myocardial viability was assessed in 55 patients (50 male; mean age 58±9 years) by 201 Tl SPECT rest-redistribution (after 4 h) scintigraphy. All patients had previous myocardial infarction (>3 months) and angiographically documented coronary artery disease, with the mean ejection fraction of 43±10%. Out of 55 patients, 20 were medically treated and 35 were revascularized. The follow-up period for adverse cardiac events, including death and non-fatal myocardial infarction, was 12 months. 201 Tl SPECT study was positive for myocardial viability in 36 patients (65%) and negative in 19 patients (35%). Sensitivity, specificity, positive and negative predictive values for functibnal improvement in the follow-up period were 85%, 75%, 92% and 60%. Out of seven (13%) cardiac events in the follow-up period (four cardiac deaths and three reinfarctions), five occurred in 20 medically treated patients and two in 35 revascularized patients (25% vs 6%, P < 0.05). Absence of myocardial viability was the only variable associated with adverse cardiac events (P = 0.02). Survival at 12 months, as determined by using Kaplan-Meier analysis, was 56% for medically treated and non-viable patients, 80% for revascularized and non-viable patients, 91% for medically treated and viable patients, and 100% for revascularized and viable patients (P=0.0034). These findings suggest that in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction, the absence of myocardial viability as determined by the 201 Tl SPECT study was the only variable associated with adverse cardiac events. The best 12 month survival was observed in revascularized viable patients, whereas the worse prognosis was found in non-viable, medically treated patients.

Chronic fatigue syndrome (CFS) is defined as constellation of the prolonged fatigue and several somatic symptoms, in the absence of organic or severe psychiatric disease. However, this is an operational definition and conclusive biomedical explanation remains elusive. Similarities between the signs and symptoms of CFS and adrenal insufficiency prompted the research of the hypothalamo-pituitary-adrenal axis (HPA) derangement in the pathogenesis of the CFS. Early studies showed mild glucocorticoid deficiency, probably of central origin that was compensated by enhanced adrenal sensitivity to ACTH. Further studies showed reduced ACTH response to vasopressin infusion. The response to CRH was either blunted or unchanged. Cortisol response to insulin induced hypoglycaemia was same as in the control subjects while ACTH response was reported to be same or enhanced. However, results of direct stimulation of the adrenal cortex using ACTH were conflicting. Cortisol and DHEA responses were found to be the same or reduced compared to control subjects. Scott et al found that maximal cortisol increment from baseline is significantly lower in CFS subjects. The same group also found small adrenal glands in some CFS subjects. These varied and inconsistent results could be explained by the heterogeneous study population due to multifactorial causes of the disease and by methodological differences. The aim of our study was to assess cortisol response to low dose (1 microgram) ACTH using previously validated methodology. We compared cortisol response in the CFS subjects with the response in control and in subjects with suppressed HPA axis due to prolonged corticosteroid use. Cortisol responses were analysed in three subject groups: control (C), secondary adrenal insufficiency (AI), and in CFS. The C group consisted of 39 subjects, AI group of 22, and CFS group of nine subjects. Subject data are presented in table 1. Low dose ACTH test was started at 0800 h with the i.v. injection of 1 microgram ACTH (Galenika, Belgrade, Serbia). Blood samples for cortisol determination were taken from the i.v. cannula at 0, 15, 30, and 60 min. Data are presented as mean +/- standard error (SE). Statistical analysis was done using ANOVA with the Games-Howell post-hoc test to determine group differences. ACTH dose per kg or per square meter of body surface was not different between the groups. Baseline cortisol was not different between the groups. However, cortisol concentrations after 15 and 30 minutes were significantly higher in the C group than in the AI group. Cortisol concentration in the CFS group was not significantly different from any other group (Graph 1). Cortisol increment at 15 and 30 minutes from basal value was significantly higher in C group than in other two groups. However, there was no significant difference in cortisol increment between the AI and CFS groups at any time of the test. On the contrary, maximal cortisol increment was not different between CFS and other two groups, although it was significantly higher in C group than in the AI group. Maximal cortisol response to the ACTH stimulation and area under the cortisol response curve was significantly larger in C group compared to AI group, but there was no difference between CFS and other two groups. Several previous studies assessed cortisol response to ACTH stimulation. Hudson and Cleare analysed cortisol response to 1 microgram ACTH in CFS and control subjects. They compared maximum cortisol attained during the test, maximum cortisol increment, and area under the cortisol response curve. There was no difference between the groups in any of the analysed parameters. However, authors commented that responses were generally low. On the contrary Scott et al found that cortisol increment at 30 min is significantly lower in the CFS than in the control group. Taking into account our data it seems that the differences found in previous studies papers are caused by the methodological differences. We have shown that cortisol increment at 15 and 30 min is significantly lower in CFS group than in C group. Nevertheless, maximum cortisol attained during the test, maximum cortisol increment, and area under the cortisol response curve were not different between the C and CFS groups. This is in agreement with our previous findings that cortisol increment at 15 minutes has the best diagnostic value of all parameters obtained during of low dose ACTH test. However, there was no difference between CFS and AI group in any of the parameters, although AI group had significantly lower cortisol concentrations at 15 and 30 minutes, maximal cortisol response, area under the cortisol curve, maximal cortisol increment, and maximal cortisol change velocity than C group. Consequently, reduced adrenal responsiveness to ACTH exists in CFS. In conclusion, we find that regarding the adrenal response to ACTH stimulation CFS subjects present heterogeneous group. In some subjects cortisol response is preserved, while in the others it is similar to one found in secondary adrenal insufficiency.

Glucocorticoids (GC) are the treatment of choice for moderate-to-severe and active Graves’ orbitopathy (GO), but optimal treatment is still undefined. The aim of the present study was to analyze the efficacy and tolerability of combined parenteral GC pulse therapy followed by oral GC in the interpulse period. The study included 50 patients (48 ± 10 years; 37 female) with untreated, active and moderate-to-severe GO. Patients received 500mg of methylprednisolone in 500ml of physiologic saline. Infusion was repeated after 48h and then followed by tapering doses of oral prednisone and the cycle repeated each month for the next 5 months. The cumulative dose was 10.2g. Ophthalmic assessment was performed before and 6 months after start of treatment. Side effects of GC therapy were evaluated and recorded each month. GC showed the greatest effectiveness on soft tissue changes (incorporated in the CAS). Median CAS values decreased from 4.5 to 2 (p>0.001). Improvement was demonstrated in 37 patients (74%), there was no change in 13 patients (26%) and none of the patients presented with deterioration of inflammatory status. Diplopia improved in 21 patients (42%), was unchanged in 28 patients (56%) and deteriorated in 1 patient (2%). Improvement in visual acuity occurred in 36% of patients. At 6 months, 33/50 patients (66%) demonstrated overall treatment response. Response to GC therapy was influenced by CAS, TSHRAb and smoking behavior. The only independent parameter associated with positive treatment response was CAS ≥4 (p

Introduction. This paper was aimed at presenting our experience and results in the surgical management for proptosis in patients with Graves` orbitopathy. Material and Methods. This is a retrospective, interventional, non-comparative case series review. Seventeen eyes of ten patients underwent orbital decompression between 2008 and 2009. Depending on case, the surgery involved one to 3 orbital walls with or without fat removal, being approached through combined transcaruncular and lower fornix incision. Results. All the operated patients were females, their mean age being 48, with proptosis ranging from 21 to 28 mm, and 18 to 22 mm three months after surgery. A mean reduction in proptosis of 4.59 ? 1.58 mm was attained. Intra-operative course was uneventful and post-operatively transient infraorbital hypoesthesia was seen in twelve patients (70.57%). Conclusion. Orbital decompression proved to be a safe, reliable and effective way to reduce proptosis provided that the procedure is carefully planned and properly performed.

Introduction Obesity is often accompanied by a number of complications including diabetes mellitus and cardiovascular diseases. Elevated blood pressure and lipids, as well as deterioration of glucoregulation are attributed, as the most significant factors, to development of diabetes mellitus and cardiovascular complications in obese patients. Objective The aim of our study was to evaluate the effects of a fasting diet on blood pressure, lipid profile and glucoregulatory parameters. Method We included 110 patients (33 male and 77 female; mean age 35?1 years, body weight 131.7?2.6 kg, body mass index 45.4?0.8 kg/m2) who were hospitalized for three weeks for the treatment of extreme obesity with the fasting diet. At the beginning, during, and at the end of this period, we evaluated changes in blood pressure, lipid profile, as well as parameters of glucoregulation including glycaemia, insulinaemia, and insulin sensitivity by HOMA. Oral glucose tolerance test (OGTT) was performed in all patients at the beginning and at the end of the fasting diet. Results During the fasting diet, the body weight decreased from 131.7?2.6 kg to 117.7?2.4 kg (p

s S183 Eur J Echocardiography Abstracts Supplement, December 2006 11 pts (8 men, mean age 60±11 years) received on top of their unchanged medication the ARB Irbesartan (300 mg two times daily, after a titration phase of 14 days) over a total of 3 months. The control group consisted of 9 pts (7 men, mean age 57±12 years) on antihypertensive treatment except ARBs or ACE-inhibitors. Exclusion criteria were relevant left ventricular hypertrophy (septum thickness >13 mm), ARBor ACE-inhibitor treatment in the last 3 month, ejection fraction

1 1 Ischaemic Heart Disease, Cardiology Dept., Yerevan, Armenia Aims: To investigate the effects of losartan with losartan at the same dose combined with colchicine therapy on ECHO- parameters, on levels of marker of inflammation high - sensivity C reactive protein (hs-CRP), leykocitosis in unstable angina (UA) patients (pts) with hyperuricaemia. To determine the nature of the relathionship between hs-CRP, increased serum uric acid lev- els, ECHO- parameters, endpoints of pts with UA. Material and methods: 46 pts (age 58.8±0.7) with UA randomly assined to treatment with losartan 50 mg once daily (group I, n=23) or a treatment with losartan at the same dose combined with colchicine 2 mg iv for the first day and then 1mg iv every 6 hour for the second day and 1 mg daily for at least 21 days (group II, n=23). The values of hs-CRP and uric acid were analysed at baseline and at 7 day. 21 days after admission pts underwent echocardio- graphy to determine left ventricular end systolic volume(ESVLV), wall motion score index (WMSI), ejection fraction (EF). The end point was defined as death, recurrent angina or nonfatal MI, need for coronary intervention, which- ever occurred in hospitalization. Results: In pts with increased levels of hs-CRP serum uric acid levels were significantly higher than in pts with normal hs-CRP values (p

Eur J Echocardiography Abstracts Supplement, December 2006 diastolic flow velocity. A >70% stenosis at quantitative coronary angiography has been considered significant. Results: A significant restenosis occurred in 49 patients (22%). There was a significant difference in basal coronary flow velocity (23.6±6.8 vs 27.4±9.7; p

of significantly stenosed coronary vessel (scored from 3-5), and (3) weighting flow factor for particular localisation. Results: Among clinical, demographical, stress echocardiographic and angiographycal variables, factors strongly associated with high mortality rates were: myocardial jeopardy score >7 (p=0.0003), positive DobAtro (p=0.016), positive DipAtro (p=0.0215) and the number of diseased vessels (p=0.005), while other variables and the results ox Ex stress echocardiography didn’t show significant influence on long-term risk of cardiac death (p=ns). Variable most strongly associated with cardiac death was myocardial jeopardy score (RR 1.05; p=0.00054). Conclusion: Patients with high amount of potentially ischemic myocardium and positive DipAtro and DobAtro stress echocardiography are at high risk for subsequent cardiac death. Myocardial jeopardy score is the strongest predictor of longterm outcome in patents with stress induced myocardial ischemia. 102 Dipyridamole stress echocardiography and ultrasonic myocardial tissue characterization in predicting myocardial ischemia, in comparison with dipyridamole stress Tc-99m MIBI SPECT myocardial imaging.

The purpose of the study was to compare diagnostic value of low dose dipyridamole radionuclide ventriculography (DIPY-RNV) and low dose dipiyidamole echocardiography (DIPY-ECHO) for the prediction of functional recovery of viable myocardium in the medium term follow up. Twenty patients (18 male; 51±10 years) with previous myocardial infarction and resting wall motion dyssynergy were studied before angioplasty of infarct related artery (IRA), by RNV and ECHO at rest, as well as during dipyridamole infusion (0,28 mcg/kg/min over 2min). RNV as well as ECHO was repeated at rest, 12 weeks after successful angioplasty. Five percent increase of regional ejection fraction (REF) by RNV was used as criterion for functional improvement of infarcted regions. By ECHO, viability was defined as improvement of wall thickening or contractile improvement of grade one or more, utilizing wall motion score index (WMSI). Out of 180 examined (20x9) segments by RNV, 51 were dyssynergic and they had abnormal REF (29±10%). Out of these 51 segments functional improvement was documented in 33 on low DIPY. Sensitivity for predicting functional recovery after 12 weeks follow up was 63%, and specificity was 77%. WMSI assessed by ECHO was 1.35±0.22, 1.16±0.20 and 1.13±0.14 for rest, low DIPY and rest follow up, respectively (p