Summary: Background: The aim of this study was to determine the reference values for thyrotropin (TSH), thyroid hormones (total and free thyroxine, T4 and fT4; total and free triiodothyronine, T3 and fT3), thyroglobulin (Tg) and thyroid antibodies (thyroid peroxidase, TPOAb and thyroglobulin antibody, TgAb) in the population of the Republic of Srpska.Methods: A total of 250 euthyroid subjects were enrolled in this study. A direct method for choosing reference subjects was used to establish reference intervals. The hormones and thyroid antibodies were measured by an electrochemiluminescence immunoassay method (ECLIA, Roche Diagnostics, Mannheim, Germany). We calculated the reference intervals by MedCalc, version 12.1.4.0 (MedCalc software, Belgium) as recommended by the IFCC (CLSI C28-A3).Results: Using guidelines recommended by the National Academy of Clinical Biochemistry (NACB) and based on standard statistical approaches, the reference intervals derived for TSH, fT4, T4, fT3, T3 were 0.75-5.32 mlU/L, 12.29-20.03 pmol/L, 73.49-126,30 nmol/L, 4.11-6.32 pmol/L, 1.15-2.32 nmol/L and for Tg, TPOAb, TgAb were 3.63-26.00 mg/L, <18.02 mlU/L, < 98.00 mlU/L, respectively. We found a significant difference (p<0.05) in TSH and fT3 values between different age groups as well as in T4, fT4 and fT3 values between gender groups.Conclusions: The established reference values for the population of the Republic of Srpska were significantly different from the values recommended by the manufacturer of reagents (Roche Diagnostics). Our results showed that a laboratory needs to establish its own reference values in order to set up a proper diagnosis, as well as to treat patients successfully.

In vitro and animal studies indicate that statins increase heme oxygenase-1 gene (HMOX1) expression, which then, presumably, increases plasma bilirubin concentration. However, clinical confirmation that statins concomitantly increase HMOX1 expression and plasma bilirubin concentration is lacking. We hypothesized that in patients with stable angina atorvastatin therapy (20 mg/day for 10 weeks) concomitantly increases total bilirubin concentration and HMOX1 expression, as assessed non-invasively by plasma analysis. In 44 patients with stable angina plasma concentrations of total bilirubin, HMOX1 mRNA and HMOX1 protein were measured before and after the statin treatment, as well as plasma concentrations of oxidized low-density lipoprotein (OxLDL), malondialdehyde (MDA), monocyte chemoattractant protein (MCP-1) and C-reactive protein (CRP). Atorvastatin treatment increased total bilirubin concentration (median 6.95 μmol/L vs. 8.55, + 23.02%; p < 0.001), but did not change plasma HMOX1 mRNA and HMOX1 protein concentrations. Plasma concentrations of OxLDL (- 31.85%, p < 0.001), MCP-1 (- 16.20%, p = 0.020) and CRP (- 7.32%, p = 0.010) were decreased but MDA was not decreased (15.32%, p = 0.107). Within subjects, increment of plasma bilirubin concentration did not correlate with the changes in HMOX1 mRNA and protein concentrations, but correlated with low-density lipoprotein cholesterol decrement (r = - 0.374, p = 0.012). Bilirubin increment did not correlate with the changes in oxidative and inflammatory markers. Our prospective observational trial finally confirms that atorvastatin (20 mg/day for 10 weeks) increases plasma total bilirubin concentration. However, it seems that this effect is HMOX1-independent.

Aim: We hypothesized that, in stable angina patients, atorvastatin therapy lowers the cathepsin S (CTSS) concentrations, as assessed non-invasively according to a plasma analysis. In addition, the low-density lipoprotein (LDL) and high-density lipoprotein (HDL) size and subclasses in the plasma were analysed to establish the association between CTSS and lipoprotein metabolism and determine whether this association is atorvastatin-sensitive. Methods: A total of 43 patients with stable angina received atorvastatin therapy (20 mg/day, 10 weeks). The plasma CTSS mRNA levels, CTSS protein concentrations and CTSS activity, as well as LDL and HDL size and subclasses, were analysed before and after treatment. Results: Atorvastatin treatment did not change the plasma CTSS mRNA levels, although it lowered the plasma CTSS concentrations and activity. An increased plasma CTSS concentration and activity were found to be associated with a more atherogenic LDL subclass profile (a decreased dominant LDL size and increased percentage of small, dense LDL particles). The atorvastatin-induced CTSS-loweringeffect was concomitant with an improvement in the LDL subclass profile, and the changes were found to be interrelated. Concomitant, interrelated changes in the CTSS levels and LDL subclass profiles were found in the LDL phenotype B patients only (a dominant LDL diameter of ≤ 25.5 nm at the start of the study). In this subgroup, lowering of the plasma CTSS mRNA level also correlated with lowering of the proportion of small, dense LDL particles. Conclusions: Atorvastatin-induced CTSS-lowering and LDL subclass profile improvements in the plasma of LDL phenotype B patients with stable angina are concomitant and interrelated.

Background: An accurate measurement of serum thyroid stimulating hormone (TSH) is crucial for a thyroid disorder diagnosis and management. We compared the values of TSH between three automated immunoassays with aims to provide insights into variations in TSH levels that are important for a clinical decision: 2.50 mIU/L, 4.00 mIU/L and 10.00 mIU/L. Methods: We measured TSH with three different fully automated immunoassays: Abbott (Architect ci8200), Siemens (ADVIA Centaur XP) and Roche (Cobas e411). Serum was collected from 110 patients between August 2018 and January 2019. The results were compared using the Passing–Bablok regression method. Additionally, linear regression coefficients were calculated after logarithmic transformation of data. Results: Although all three regression coefficients were high (r² > 0.98), the slopes from Passing–Bablok plots for the correlation of Abbott with either Roche or Siemens were merely 0.66 and 0.73, respectively. The slope for the correlation of Roche and Siemens was 1.11. Consecutively, the results obtained by the Roche and Siemens methods were proportionally higher than those obtained by the Abbott method (38% and 52%, respectively) at all measured ranges. Conclusions: Although immunoassays correlated among themselves, they cannot achieve the same values for clinical decisions for hypothyroidism (clinical requirements). Clinicians should be conscious of these limitations. A harmonisation of the methods is needed to meet clinical requirements and to enable appropriate clinical decisions in cases of hypothyroidism. Likewise, we suggest the introduction of borderline and high risk values of TSH for hypothyroidism depending on immunoassays to avoid misdiagnosis.

Background/Aim: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, characterized by the production of numerous pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), which lead to pathophysiological changes in innate and acquired immunity. The existing evidence shows that pro-inflammatory cytokines in rheumatoid arthritis impact monoaminergic neurotransmission, neurotropic factors, and synaptic activity, which may lead to the development of depression. Materials and Methods: In our study, we explored the association between TNF-α and IL-6, disease activity, and the degree of depression in patients with RA. The association between TNF-α and IL-6 and the Beck and Hamilton depression scales was analyzed in a group of 116 RA patients with depression. We investigated the same correlation in 45 patients with primary depression who represented the control group. Results: A Spearman test showed that IL-6 levels had a positive association with the Beck and Hamilton scales (p < 0.05) and that TNF-α had a positive association with the Hamilton scale (p < 0.05). Also, the Hamilton depression scale was the more sensitive scale in the detection of depressive symptoms. Conclusions: Our study indicates that elevated values of pro-inflammatory cytokines are associated with the degree of depression in patients with RA. Future preclinical and clinical studies will contribute to a better understanding of the pathophysiological mechanism of depression in patients with RA and may serve as the basis for new treatment modalities. By detecting depression promptly, with the help of the HAM-D as the more sensitive scale, we could influence the future modality of treatment, and with a multidisciplinary approach, we could ensure an improvement in the quality of life of patients with RA.