Browsing by Author "Zarkovic, Milos (7003498546)"

Because of the high mortality rate of thyroid storm (TS), effective guidance for its diagnosis and treatment is essential. The diagnostic criteria introduced by the Japanese Thyroid Association in 2012, along with the Burch-Wartofsky Point Scale, constitute valuable tools for the diagnosis of TS. In 2016, Guidelines on the management of TS were produced by the Japanese Thyroid Association and the Japanese Endocrine Society. Recently, a prospective multicenter register-based study compared the prognosis and outcome of 110 new-onset TS patients with the results of previous comparable studies and evaluated the efficacy of the Guidelines. The study revealed higher Acute Physiology and Chronic Health Evaluation II scores and significant correlations between lower body mass index, postresuscitation shock, and fever with outcomes and, overall, improved TS prognosis. Most patients in the study received methimazole and potassium iodide, the timely administration of which was linked to lower fatality rates. Adherence to treatment guidelines correlates with lower mortality rates, emphasizing the importance of experienced multidisciplinary teams in intensive care unit settings and the necessity for periodic review of the guidelines to enhance therapeutic approaches and reduce mortality. © 2024 The Author(s).

Because of the high mortality rate of thyroid storm (TS), effective guidance for its diagnosis and treatment is essential. The diagnostic criteria introduced by the Japanese Thyroid Association in 2012, along with the Burch-Wartofsky Point Scale, constitute valuable tools for the diagnosis of TS. In 2016, Guidelines on the management of TS were produced by the Japanese Thyroid Association and the Japanese Endocrine Society. Recently, a prospective multicenter register-based study compared the prognosis and outcome of 110 new-onset TS patients with the results of previous comparable studies and evaluated the efficacy of the Guidelines. The study revealed higher Acute Physiology and Chronic Health Evaluation II scores and significant correlations between lower body mass index, postresuscitation shock, and fever with outcomes and, overall, improved TS prognosis. Most patients in the study received methimazole and potassium iodide, the timely administration of which was linked to lower fatality rates. Adherence to treatment guidelines correlates with lower mortality rates, emphasizing the importance of experienced multidisciplinary teams in intensive care unit settings and the necessity for periodic review of the guidelines to enhance therapeutic approaches and reduce mortality. © 2024 The Author(s).

Background: The presence of glutathione transferase (GST) M1 null genotype (GSTM1-null) in end-stage renal disease (ESRD) patients is associated with lower overall survival rate in comparison to those with GSTM1-active variants. We examined association between GSTM1 and GSTT1 deletion polymorphisms as well as SNPs in GSTA1/rs3957357 and GSTP1/rs1695 genes with overall and cause-specific cardiovascular mortality in ESRD patients. Methods. Total of 199 patients undergoing hemodialysis were included in the study. Median value of time elapsed from dialysis initiation until the death, or the end of follow-up was 8 ± 5 years. The effect of GSTM1, GSTT1, GSTP1 and GSTA1 gene polymorphisms on predicting overall and specific cardiovascular outcomes (myocardial infarction, MI or stroke) was analyzed using Cox regression model, and differences in survival were determined by Kaplan-Meier. Results: GSTM1-null genotype in ESRD patients was found to be independent predictor of overall and cardiovascular mortality. However, after false discovery rate and Bonferroni corrections this effect was lost. The borderline effect modification by wild-type GSTA1*A/*A genotype on associations between GSTM1-null and analyzed outcomes was found only for death from stroke. Homozygous carriers of combined GSTM1*0/GSTA1*A genotype exhibited significantly shorter time to death of stroke or MI in comparison with carriers of either GSTM1-active or at least one GSTA1*B gene variant. The best survival rate regarding cardiovascular outcome was found for ESRD patients with combined GSTM1-active and mutant GSTA1*B/*B genotype. Conclusions: Combined GSTM1*0/GSTA1*A genotypes might be considered as genetic markers for cardiovascular death risk in ESRD patients, which may permit targeting of preventive and early intervention. © 2014 Suvakov et al.; licensee BioMed Central Ltd.

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. © 2020 John Wiley & Sons Ltd

(Ivkovic D, Markovic M, Todorovic BS, Balestra C, Marroni A, Zarkovic M. Effect of a single pool dive on pulmonary function in asthmatic and non-asthmatic divers. Diving and Hyperbaric Medicine. 2012;42(2):72-77.) Introduction: The aim of this study was to evaluate the effect of a single, shallow, swimming pool scuba dive on pulmonary function in divers with asthma as compared to controls. Opinions concerning the risks of diving with asthma are still contradictory and inconclusive in the diving community. Methods: Baseline pulmonary function tests (PFTs) were performed on a group of 22 divers with asthma and on a control group of 15 healthy divers. The same PFTs were repeated within 10 minutes after a single pool dive, at 5 metres' depth for 10 minutes. PFTs were measured using a portable Jaeger SpiroPro™ device. Student's paired t-tests and linear mixed effects model comparisons and interactions within the groups were used in the data analysis. Results: Divers with asthma initially presented significantly lower values of FEV1/FVC%* (P < 0.01), FEF 25* (P < 0.01), FEF50* (P < 0.001), FEF75* (P < 0.01) and FEF 25-75* (P < 0.001) compared to controls. There were significant reductions in FEV1 (P < 0.01), FEV 1/FVC% (P < 0.05), FEF 50* (P < 0.01), FEF 75* (P < 0.05) and FEF25-75* (P < 0.001), in the asthma group after the dive as comparied to the control group. PEF was initially lower, although not significantly, in the asthma group and did not change significantly after the dive in either groups (P > 0.05). Conclusions: A single, shallow, pool scuba dive to 5 metres' depth may impair function of small airways in asthmatic divers. More studies are necessary to estimate the risks when divers with asthma practise scuba diving. PFT results should be analysed after replicated dives in deeper pools and controlled open-water conditions.

Objective: 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. Design: 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. RESU LTS: 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<0.001). Side effects occurred in 35/50 patients (70%) and the vast majority of them were mild to moderate. During the 6-months follow-up period, 2/33 patients (6%) had relapsing GO. Conclus Ion: With appropriate selection of patients and careful monitoring during and after treatment, combined parenteral and oral GC therapy is effective and safe.

Graves' ophthalmopathy (GO) is an autoimmune disease affecting ocular and orbital tissues. Overproduction of tumor necrosis factor α (TNF-α) in rheumatoid arthritis (RA) and GO has destructive consequences. The subject of this paper is a case of a female patient initially diagnosed with primary hypothyroidism substitution with levothyroxine, and subsequent diagnosis of RA with insufficient therapeutic efficacy of a standard medication. Three years later, the patient presented symptoms and signs of GO. Etanercept was administrated for RA, and after four months, an improvement of the eye symptoms and reduced exophthalmos were observed and confirmed using visual methods. Graves' ophthalmopathy association with primary hypothyroidism is uncommon. The treatment of RA using etanercept led to clinical improvement of GO symptoms, which indicates that RA and GO may share similar pathogenic features. The paper suggests that etanercept may suppress the symptoms and clinical signs of GO. However, controlled trials are needed to further evaluate the effect of TNF-α inhibitors, particularly etanercept, and to compare its side effects with the current options for medical treatment. © 2019 Termedia Publishing House Ltd.. All rights reserved.

Graves' ophthalmopathy (GO) is an autoimmune disease affecting ocular and orbital tissues. Overproduction of tumor necrosis factor α (TNF-α) in rheumatoid arthritis (RA) and GO has destructive consequences. The subject of this paper is a case of a female patient initially diagnosed with primary hypothyroidism substitution with levothyroxine, and subsequent diagnosis of RA with insufficient therapeutic efficacy of a standard medication. Three years later, the patient presented symptoms and signs of GO. Etanercept was administrated for RA, and after four months, an improvement of the eye symptoms and reduced exophthalmos were observed and confirmed using visual methods. Graves' ophthalmopathy association with primary hypothyroidism is uncommon. The treatment of RA using etanercept led to clinical improvement of GO symptoms, which indicates that RA and GO may share similar pathogenic features. The paper suggests that etanercept may suppress the symptoms and clinical signs of GO. However, controlled trials are needed to further evaluate the effect of TNF-α inhibitors, particularly etanercept, and to compare its side effects with the current options for medical treatment. © 2019 Termedia Publishing House Ltd.. All rights reserved.

Background/Objectives: The thyroid gland has an important influence on the heart. Long-term exposure to high levels of thyroid hormones may lead to cardiac hypertrophy and dysfunction. The aim of the study was to evaluate the morphological and functional changes in the left ventricle in patients with hyperthyroidism caused by Graves’ disease (GD) in comparison with healthy individuals, as well as to investigate potential differences in these parameters in GD patients in relation to the presence of orbitopathy. Methods: The prospective study included 39 patients with clinical manifestations and laboratory confirmation of GD and 35 healthy controls. All participants underwent a detailed echocardiographic examination. The groups were compared according to demographic characteristics (age and gender), heart rate and echocardiographic characteristics. Results: The patients with hyperthyroidism caused by GD had significantly higher values of left ventricular diameter, left ventricular volume and left ventricular mass compared to the healthy controls. In addition, hyperthyroidism significantly influenced the left ventricular contractility and led to the deterioration of the systolic and diastolic function, as shown together by longitudinal strain, color Doppler and tissue Doppler imaging. However, the patients with GD and orbitopathy showed better left ventricular function than those without orbitopathy. Conclusions: Besides the confirmation of previously known findings, our study indicates possible differences in echocardiographic parameters in GD patients in relation to the presence of orbitopathy. Further investigation with larger samples and meta-analyses of data focused on the evaluation of echocardiographic findings in the context of detailed biochemical and molecular analyses is required to confirm our preliminary results and their clinical significance. © 2024 by the authors.

Introduction: Nickel (Ni) is one of the well-known toxic metals found in the environment. However, its influence on thyroid function is not explored enough. Hence, the aim of this study was to analyse the potential of Ni to disrupt thyroid function by exploring the relationship between blood Ni concentration and serum hormone levels (TSH, T4, T3, fT4 and fT3), as well as the parameters of thyroid homeostasis (SPINA-GT and SPINA-GD) by using correlation analysis and Benchmark (BMD) concept. Methods: Ni concentration was measured by ICP-MS method, while CLIA was used for serum hormone determination. SPINA Thyr software was used to calculate SPINA-GT and SPINA-GD parameters. BMD analysis was performed by PROAST software (70.1). The limitations of this study are the small sample size and the uneven distribution of healthy and unhealthy subjects, limited confounding factors, as well as the age of the subjects that could have influenced the obtained results. Results and discussion: The highest median value for blood Ni concentration was observed for the male population and amounted 8,278 µg/L. Accordingly, the statistically significant correlation was observed only in the male population, for Ni-fT4 and Ni-SPINA-GT pairs. The existence of a dose-response relationship was established between Ni and all the measured parameters of thyroid functions in entire population and in both sexes. However, the narrowest BMD intervals were obtained only in men, for Ni - SPINA-GT pair (1.36-60.9 µg/L) and Ni - fT3 pair (0.397-66.8 µg/L), indicating that even 78.68 and 83.25% of men in our study might be in 10% higher risk of Ni-induced SPINA-GT and fT3 alterations, respectively. Due to the relationship established between Ni and the SPINA-GT parameter, it can be concluded that Ni has an influence on the secretory function of the thyroid gland in men. Although the further research is required, these findings suggest possible role of Ni in thyroid function disturbances. Copyright © 2023 Maric, Baralic, Javorac, Mandic-Rajcevic, Zarkovic, Antonijevic, Djukic-Cosic, Bulat and Djordjevic.

Subclinical hypothyroidism (SH) is characterized by a mildly elevated concentration of thyroid stimulating hormone (TSH) despite free thyroxine (FT4) and triiodothyronine (FT3) levels within the reference range. Numerous studies revealed SH to be an independent risk factor for cardiovascular disease (CVD), including atherosclerosis, congestive heart failure, coronary heart disease, ischemic heart disease and the associated mortality. The relationship between SH and CVD is well documented, but the molecular mechanism underlying this correlation remain unknown. Endothelial dysfunction has been recognized as an initial step leading to CVD in patients with SH. Changes in lipid profile, inflammation and/or oxidative stress contribute to the endothelial dysfunction in SH. Moreover, the progression of SH is characterized by significantly decreased nitrite and nitrate levels. Recent animal and clinical studies discussed in this review suggest that nitric oxide (NO) levels could be a reliable biomarker for cardiovascular risk in SH. Understanding the regulation of NO production by thyroid hormone may provide novel and useful knowledge regarding how endothelial dysfunction in SH is linked with CVD and help us to uncover new treatments for SH. We suggest that serum NO level may be an indicator for the introduction and dosage of levothyroxine (LT4) replacement therapy in SH patients. Future studies should focus on understanding the molecular mechanisms underlying the effects of NO in physiological as well as in pathophysiological conditions such as hypothyroidism and their clinical relevance. © 2016 Bentham Science Publishers.

Background: Higher levels of thyroid autoantibodies in follicular fluid (FF) of thyroid autoimmunity (TAI) positive women are strongly correlated with serum levels and may have effect on the post-implantation embryo development. Literature highlights that levothyroxine (LT4) treatment may attenuate the risk of adverse pregnancy outcomes. The aim of the study was to estimate the pregnancy and newborn outcomes in women with FF thyroid autoantibodies undergoing assisted reproductive technology (ART). Methods: The study population included 24 women with confirmed clinical pregnancy, 8 TAI positive and 16 TAI negative women. LT4 supplementation was applied in 20.8% patients, TAI positive. Results: Pregnancy outcomes were: twin pregnancy rate 41.7%, early miscarriage rate 8.3%, late miscarriage rate 4.2%, preterm birth rate 16.7%, term birth rate 70.8%, live birth rate 96.0%. There was significant difference in serum and in FF TgAbs (p<0.001)between the groups according to TAI, while serum fT3was lower in the group with TAI (p=0.047). Serum fT4was higher in LT4 treated group (p=0.005), with TAI, and newborns in this group had higher birth weight (p=0.001) and height (p=0.008). Maternal complications occurred in 23.8% of patients. No congenital malformations in newborns were noted. Conclusions: Thyroid autoantibodies present in FF may have an effect on the post-implantation embryo development, but have no effect on further course of pregnancy. The special benefit of LT4 treatment for successful ART outcome was demonstrated for newborn anthropometric parameters. © 2023 Sciendo. All rights reserved.

Background: Higher levels of thyroid autoantibodies in follicular fluid (FF) of thyroid autoimmunity (TAI) positive women are strongly correlated with serum levels and may have effect on the post-implantation embryo development. Literature highlights that levothyroxine (LT4) treatment may attenuate the risk of adverse pregnancy outcomes. The aim of the study was to estimate the pregnancy and newborn outcomes in women with FF thyroid autoantibodies undergoing assisted reproductive technology (ART). Methods: The study population included 24 women with confirmed clinical pregnancy, 8 TAI positive and 16 TAI negative women. LT4 supplementation was applied in 20.8% patients, TAI positive. Results: Pregnancy outcomes were: twin pregnancy rate 41.7%, early miscarriage rate 8.3%, late miscarriage rate 4.2%, preterm birth rate 16.7%, term birth rate 70.8%, live birth rate 96.0%. There was significant difference in serum and in FF TgAbs (p<0.001)between the groups according to TAI, while serum fT3was lower in the group with TAI (p=0.047). Serum fT4was higher in LT4 treated group (p=0.005), with TAI, and newborns in this group had higher birth weight (p=0.001) and height (p=0.008). Maternal complications occurred in 23.8% of patients. No congenital malformations in newborns were noted. Conclusions: Thyroid autoantibodies present in FF may have an effect on the post-implantation embryo development, but have no effect on further course of pregnancy. The special benefit of LT4 treatment for successful ART outcome was demonstrated for newborn anthropometric parameters. © 2023 Sciendo. All rights reserved.

Background: Although thyroid hormones have significant effect on cardiovascular system, the impact of subtle thyroid dysfunction such as subclinical hypothyroidism (SCH) remains to be determined. We investigated coronary flow reserve (CFR) in patients with subclinical hypothyroidism. Methods: Thirty two subjects with SCH and eighteen control subjects with normal serum thyroid hormones and thyroid-stimulating hormone (TSH) levels were included in the study. TSH, free thyroxine, free triiodothyronine, glucose, insulin, HbA1c, cholesterol, triglyceride and plasma levels of C-reactive protein were measured. Coronary diastolic peak flow velocities in left anterior descending coronary artery were measured at baseline and after adenosine infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocity. Results: CFR values were not significantly different between the two groups (SCH 2.76±0.35 vs controls 2.76±0.42). There was a significant correlation of CFR with waist to hip ratio, hypertension, smoking habits, markers of glucose status (glucose level, HbA1c, insulin level, HOMA IR), cholesterol, LDL-cholesterol and triglyceride levels in SCH group, whereas only cholesterol level showed significant correlation with CFR in controls. There was no correlation between CFR and thyroid hormones. Conclusions: We concluded that there is a different impact of cardiovascular risk factors on CFR in SCH patients compared to healthy control and that these two groups behave differently in the same circumstances under the same risk factors. The basis for this difference could be that the altered thyroid axis»set point« changes the sensitivity of the microvasculature in patients with SCH to known risk factors. © 2022 Sciendo. All rights reserved.

Background: Although thyroid hormones have significant effect on cardiovascular system, the impact of subtle thyroid dysfunction such as subclinical hypothyroidism (SCH) remains to be determined. We investigated coronary flow reserve (CFR) in patients with subclinical hypothyroidism. Methods: Thirty two subjects with SCH and eighteen control subjects with normal serum thyroid hormones and thyroid-stimulating hormone (TSH) levels were included in the study. TSH, free thyroxine, free triiodothyronine, glucose, insulin, HbA1c, cholesterol, triglyceride and plasma levels of C-reactive protein were measured. Coronary diastolic peak flow velocities in left anterior descending coronary artery were measured at baseline and after adenosine infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocity. Results: CFR values were not significantly different between the two groups (SCH 2.76±0.35 vs controls 2.76±0.42). There was a significant correlation of CFR with waist to hip ratio, hypertension, smoking habits, markers of glucose status (glucose level, HbA1c, insulin level, HOMA IR), cholesterol, LDL-cholesterol and triglyceride levels in SCH group, whereas only cholesterol level showed significant correlation with CFR in controls. There was no correlation between CFR and thyroid hormones. Conclusions: We concluded that there is a different impact of cardiovascular risk factors on CFR in SCH patients compared to healthy control and that these two groups behave differently in the same circumstances under the same risk factors. The basis for this difference could be that the altered thyroid axis»set point« changes the sensitivity of the microvasculature in patients with SCH to known risk factors. © 2022 Sciendo. All rights reserved.