Miloš Žarković

PREGO (presentation of Graves’ orbitopathy) study: changes in referral patterns to European Group On Graves’ Orbitopathy (EUGOGO) centres over the period from 2000 to 2012

Background/aims The epidemiology of Graves’ orbitopathy (GO) may be changing. The aim of the study was to identify trends in presentation of GO to tertiary centres and initial management over time. Methods Prospective observational study of European Group On Graves’ Orbitopathy (EUGOGO) centres. All new referrals with a diagnosis of GO over a 4-month period in 2012 were included. Clinical and demographic characteristics, referral timelines and initial decisions about management were recorded. The data were compared with a similar EUGOGO survey performed in 2000. Results The demographic characteristics of 269 patients studied in 2012 were similar to those collected in the year 2000, including smoking rates (40.0% vs 40.2%). Mild (60.5% vs 41.2%, p<0.01) and inactive GO (63.2% vs 39.9%, p<0.01) were more prevalent in 2012. The times from diagnosis of thyroid disease to being seen in EUGOGO centres (6 vs 16 months) and from first symptoms of GO (9 vs 16 months) or from diagnosis of GO (6 vs 12 months) to first consultation in EUGOGO centres were shorter in 2012 (p<0.01). The initial management plans for GO were no different except surgical treatments for patients with mild inactive disease were more frequently offered in the 2012 cohort than in 2000 (27.3% vs 17%, p<0.05), and selenium supplements were offered only in the 2012 cohort (21.2% vs 0%, p<0.01). Conclusions These findings suggest that the clinical manifestations of patients with GO may be changing over time in Europe.

Indirect estimation of age-related reference limits of thyroid parameters: A cross-sectional study of outpatients’ results

Abstract Objectives. Defining adequate reference limits (RLs) for thyroid hormones is an important task for support monitoring and the treatment of subclinical thyroid disease. We determined whether there are age-related RLs for thyroid parameters in male and female outpatients free of overt thyroid disease. Design. We analyzed 22,860 results (11,440 male and 11,420 female outpatients above the age of 18) for thyrotropin (TSH), free thyroxine (fT4) and total triiodothyronine (T3) that were stored in our laboratory information system between 2008 and 2011. We calculated the 2.5th and 97.5th centiles for the analyzed thyroid parameters. Results. Our results indicate higher TSH levels with ageing, with a significant difference (p < 0.05) between the 97.5th centiles for males and females older than 70 (5.07 mIU/L and 4.10 mIU/L), but also a significant difference between male and female fT4 from 31 to 40 and from 41 to 50 years old (18.4 vs 14.9 pmol/L and 19.0 vs 15.9 pmol/L, p < 0.05), respectively. Overall indirect estimates of the 97.5th centiles for TSH for males and females were not significantly different and were below the generally recommended upper limit (4.01 mIU/L and 4.20 mIU/L, respectively). In addition, we found no statistically significant change in mean T3 values in the analyzed population. Conclusions. This cross-sectional study indicates change in TSH and fT4 levels with ageing and gender-related upper limits. This suggests that by using indirect estimation a laboratory could provide clinicians with more accurate gender- and age-specific RLs for thyroid parameters.

The value of multidetector computed tomography of orbits in globe protrusion in comparison to hertel exophthalmometry

The use of multidetector computed tomography (MDCT) is an integral part of contemporary diagnostics of Graves‘ orbitopathy. The aim of this study was to assess proptosis measurement by MDCT and to compare it to the current standard, Hertel exophthalmometry. A cross-sectional study was conducted at the Clinical Centre of Serbia and included 91 patients (19 male and 72 female) with verified Graves‘ orbitopathy. Globe protrusion measured by MDCT (globe protrusion, GPR) was correlated to Hertel measured protrusion (HR). There was no constant or any systematic bias between the two methods. GPR significantly correlated with the best-corrected visual acuity, while HR did not. Age, body mass index and duration of the disease did not influence proptosis measurement by either method. Proptosis was significantly larger in males. According to our results, GPR compared to HR provides better assessment of the protrusion in Graves‘ disease. GPR measurement is simple and should always be part of the radiological assessment of orbits in Graves‘ disease.

Environmental and take-home lead exposure in children living in the vicinity of a lead battery smelter in Serbia

ABSTRACT Blood lead levels (BLLs) have been falling steadily worldwide due to restricted use of lead (Pb) and its compounds. although they remain above preindustrial Pb levels. Elevated BLL can still be found in children living near secondary Pb smelters that represent around 50% of Pb production. There have been no studies on Pb exposure in children living in Serbia ever since the 1980s. The aim of this study was to evaluate the BLLs in children living in two villages in Serbia (Zajača, the location of a secondary lead smelter, and Paskovac, 5 km away), identify the primary determinants of children’s BLLs, and investigate the impact of BLLs on children’s health symptoms and school achievement. The study was conducted in 2011 on 127 children, aged 1–18 years, whose BLLs were measured using inductively coupled argon plasma mass spectrometry (ICP‐MS). The median BLL in children was 12 &mgr;g/dl, with a significantly higher value of 17.5 &mgr;g/dl in Zajača, compared to 7.6 &mgr;g/dl in Paskovac. Only 1 out of 75 and 12 out of 52 children from Zajača and Paskovac, respectively, had BLLs below the CDC recommended 5 &mgr;g/dl level. Living near the smelter resulted in 19 times, and having a father who works in the plant 4 times higher odds of elevated BLLs. No significant effects of elevated BLLs health symptoms were seen in this study. BLLs of children living near a battery recycling plant in Serbia, an upper‐middle income European country, were in the range and even higher than those of children living in developing countries. For the first time, the contribution of environmental and take‐home lead exposure was quantified using mixed‐effect modeling, and our results indicate a contribution of 25–40% of the take‐home lead exposure to the BLLs of children living in the vicinity of a secondary lead smelter. HighlightsChildren living near a battery recycling plant had elevated blood lead levels (BLLs).Children 0–6 years old living closest to the plant had the highest BLLs.Higher lead exposure was found in children whose fathers worked in the plant.The contribution of take‐home lead exposure was between 25% and 40%.

Variability of HOMA and QUICKI insulin sensitivity indices

Abstract 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.