Browsing by Author "Bogavac, Tamara (57191923071)"

Objective: There are limited data on cardiometabolic risk factors and the prevalence of metabolic syndrome (MetS) across the different PCOS phenotypes in Caucasian population. Lipid accumulation product (LAP) is a clinical surrogate marker that could be used for evaluation of MetS in clinical practice. The aim of the study was to analyze metabolic characteristics and the ability of LAP to predict MetS in different PCOS phenotypes. Design: Cross-sectional clinical study analyzing 365 women with PCOS divided into four phenotypes according to the ESHRE/ASRM criteria, and 125 healthy BMI-matched controls. Methods: In all subjects, LAP was determined and MetS was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III (NCEP-ATP III), the International Diabetes Federation (IDF) and the Joint Interim Statement (JIS) criteria. Logistic regression and ROC curve analyses were used to determine predictors of MetS in each PCOS phenotype. All analyses were performed with age and BMI adjustment. Results: All PCOS phenotypes in comparison to controls had higher prevalence of MetS assessed by NCEP-ATP III criteria, and only classic phenotypes when IDF and JIS criteria were used. All phenotypes had the same prevalence of MetS irrespective of used definition. LAP and exhibited the highest diagnostic accuracy and was an independent predictor of MetS in all phenotypes. Conclusion: LAP is an independent and accurate clinical determinant of MetS in all PCOS phenotypes in our Caucasian population. All PCOS phenotypes, including non-classic ones, are metabolically challenged and with cardiovascular risk, particularly phenotype B. © 2016 The authors Published by Bioscientifica Ltd.

Objective: There are limited data on cardiometabolic risk factors and the prevalence of metabolic syndrome (MetS) across the different PCOS phenotypes in Caucasian population. Lipid accumulation product (LAP) is a clinical surrogate marker that could be used for evaluation of MetS in clinical practice. The aim of the study was to analyze metabolic characteristics and the ability of LAP to predict MetS in different PCOS phenotypes. Design: Cross-sectional clinical study analyzing 365 women with PCOS divided into four phenotypes according to the ESHRE/ASRM criteria, and 125 healthy BMI-matched controls. Methods: In all subjects, LAP was determined and MetS was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III (NCEP-ATP III), the International Diabetes Federation (IDF) and the Joint Interim Statement (JIS) criteria. Logistic regression and ROC curve analyses were used to determine predictors of MetS in each PCOS phenotype. All analyses were performed with age and BMI adjustment. Results: All PCOS phenotypes in comparison to controls had higher prevalence of MetS assessed by NCEP-ATP III criteria, and only classic phenotypes when IDF and JIS criteria were used. All phenotypes had the same prevalence of MetS irrespective of used definition. LAP and exhibited the highest diagnostic accuracy and was an independent predictor of MetS in all phenotypes. Conclusion: LAP is an independent and accurate clinical determinant of MetS in all PCOS phenotypes in our Caucasian population. All PCOS phenotypes, including non-classic ones, are metabolically challenged and with cardiovascular risk, particularly phenotype B. © 2016 The authors Published by Bioscientifica Ltd.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant cancer syndrome characterized by the occurrence of primary hyperparathyroidism (PHPT), pituitary adenoma (PA) and pancreatic neuroendocrine tumor (pNET). Whether the underlying mutations in MEN1 gene predict clinical presentation of affected heterozygotes or not, is still a matter of a debate. Methods: Clinical and genetic analysis of 90 consecutive MEN1 patients was performed in a retrospective, single - center study. Results: MEN1 mutation was found in 67 (74.4%) patients belonging to 31 different families. Twenty nine different heteozygous mutations were found, including 6 novel point mutations (W220G, 941delG, 1088del7, 1184insA, 1473del10, 1602del17) and one large deletion of exon 8. Truncating mutations predicted development of pNETs (OR=5.8, 95% CI 1.7 - 19.7%) and PHPT (OR=4.3, 95% CI 1.5 - 12.4%). Conclusions: Large number of novel mutations among MEN1 patients confirmed previously reported data. PNETs and PHPT were more frequent in patients with truncating mutations. © 2019 Tatjana Isailovic et al., published by Sciendo 2019.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant cancer syndrome characterized by the occurrence of primary hyperparathyroidism (PHPT), pituitary adenoma (PA) and pancreatic neuroendocrine tumor (pNET). Whether the underlying mutations in MEN1 gene predict clinical presentation of affected heterozygotes or not, is still a matter of a debate. Methods: Clinical and genetic analysis of 90 consecutive MEN1 patients was performed in a retrospective, single - center study. Results: MEN1 mutation was found in 67 (74.4%) patients belonging to 31 different families. Twenty nine different heteozygous mutations were found, including 6 novel point mutations (W220G, 941delG, 1088del7, 1184insA, 1473del10, 1602del17) and one large deletion of exon 8. Truncating mutations predicted development of pNETs (OR=5.8, 95% CI 1.7 - 19.7%) and PHPT (OR=4.3, 95% CI 1.5 - 12.4%). Conclusions: Large number of novel mutations among MEN1 patients confirmed previously reported data. PNETs and PHPT were more frequent in patients with truncating mutations. © 2019 Tatjana Isailovic et al., published by Sciendo 2019.

Objectives: To investigate whether BclI polymorphism in the glucocorticoid receptor gene influences hypothalamic-pituitary-adrenal (HPA) axis regulation, body composition and metabolic parameters in women with adrenal incidentalomas (AIs). Study design: A cross-sectional study. Main outcome measures: We analyzed 106 women with AIs. Insulin resistance was assessed using a homeostasis model while HPA activity was assessed using dexamethasone suppression tests (DST), basal ACTH, urinary free cortisol, and midnight serum cortisol level. Body composition was analyzed using dual-energy X-ray absorptiometry. DNA was obtained from peripheral blood leucocytes and BclI polymorphism was detected using PCR, RFLP and DNA sequencing. Results: BclI carriers in comparison with those with wild-type BclI had less suppressed cortisol after DST-0.5 mg (126.4 ± 111.4 vs 80.9 ± 75.7 nmol/l, p = 0.026) and had a lower prevalence of impaired glucose tolerance and of type 2 diabetes mellitus (T2DM). BclI carriers had a higher percentage of leg fat mass (FM), lower left-sided limb muscle mass and a decline in total lean body mass. Duration of menopause remained a strong predictor of appendicular lean mass index (ALMI) (β=-0.125, p = 0.034). BclI polymorphism was significantly associated with sum of legs FM percentage (β=0.327, p = 0.048). T2DM was negatively associated with BclI polymorphism, after adjusting for age, truncal FM, ALMI, and sum of legs FM (OR=0.158, 95%CI 0.031–0.806, p = 0.027). Conclusions: BclI polymorphism is associated with tissue-specific glucocorticoid sensitivity, relative glucocorticoid resistance of the HPA axis and peripheral adipose tissue, and glucocorticoid hypersensitivity at the muscle level. By modulating glucocorticoid and insulin sensitivity, BclI polymorphism appears to reduce the risk of T2DM in women with AIs. © 2021 Elsevier B.V.

Objectives: To investigate whether BclI polymorphism in the glucocorticoid receptor gene influences hypothalamic-pituitary-adrenal (HPA) axis regulation, body composition and metabolic parameters in women with adrenal incidentalomas (AIs). Study design: A cross-sectional study. Main outcome measures: We analyzed 106 women with AIs. Insulin resistance was assessed using a homeostasis model while HPA activity was assessed using dexamethasone suppression tests (DST), basal ACTH, urinary free cortisol, and midnight serum cortisol level. Body composition was analyzed using dual-energy X-ray absorptiometry. DNA was obtained from peripheral blood leucocytes and BclI polymorphism was detected using PCR, RFLP and DNA sequencing. Results: BclI carriers in comparison with those with wild-type BclI had less suppressed cortisol after DST-0.5 mg (126.4 ± 111.4 vs 80.9 ± 75.7 nmol/l, p = 0.026) and had a lower prevalence of impaired glucose tolerance and of type 2 diabetes mellitus (T2DM). BclI carriers had a higher percentage of leg fat mass (FM), lower left-sided limb muscle mass and a decline in total lean body mass. Duration of menopause remained a strong predictor of appendicular lean mass index (ALMI) (β=-0.125, p = 0.034). BclI polymorphism was significantly associated with sum of legs FM percentage (β=0.327, p = 0.048). T2DM was negatively associated with BclI polymorphism, after adjusting for age, truncal FM, ALMI, and sum of legs FM (OR=0.158, 95%CI 0.031–0.806, p = 0.027). Conclusions: BclI polymorphism is associated with tissue-specific glucocorticoid sensitivity, relative glucocorticoid resistance of the HPA axis and peripheral adipose tissue, and glucocorticoid hypersensitivity at the muscle level. By modulating glucocorticoid and insulin sensitivity, BclI polymorphism appears to reduce the risk of T2DM in women with AIs. © 2021 Elsevier B.V.

Background: Adrenal incidentalomas (AI) are clinically silent adrenal masses that are detected incidentally during imaging procedures performed for unrelated diseases. The aim of this study was to investigate the prevalence of subclinical hypercortisolism (SH) and associated co-morbidities in patients with unilateral AI (UAI) and bilateral AI (BAI). Methods: We evaluated 152 patients, 105 (69.1%) with UAI and 47 (30.9%) with BAI. SH was diagnosed in the presence of serum cortisol levels after 1 mg dexamethasone suppression test (DST) or after 2-day low-dose DST (LDDST) > 50 nmol/L with at least one of the following parameters: midnight serum cortisol > 208 nmol/L, 24-h urinary free cortisol > 245 nmol/24 h, or ACTH < 10 ng/L. Bone mineral density (BMD) was measured at lumbar spine (LS) and femoral neck (FN). Results: Age, BMI, and waist circumference were comparable, and diabetes, hypertension and dyslipidemia occurred with similar frequency in both groups. The overall prevalence of SH was 20.5% based on post-1 mg DST, and 20.0% based on post-LDDST cortisol levels, and it was more prevalent in BAI than UAI patients (31.1% vs 15.2%, respectively, p=0.026). LS BMD was lower in BAI than in UAI patients (0.96±0.14 vs 0.87±0.15, p=0.002). There were no differences in FN BMD. The prevalence of osteoporosis was higher in BAI compared to UAI patients (37.1% vs 15.9%, respectively, p=0.011). Conclusions: Patients with BAI had higher prevalence of SH and osteoporosis than those with UAI. Frequency of other co-morbidities was similar. This may be due to the higher degree of autonomous cortisol secretion or different tissue-specific sensitivity to glucocorticoids. © 2016 Sanja Ognjanović et al.

Background: Adrenal incidentalomas (AI) are clinically silent adrenal masses that are detected incidentally during imaging procedures performed for unrelated diseases. The aim of this study was to investigate the prevalence of subclinical hypercortisolism (SH) and associated co-morbidities in patients with unilateral AI (UAI) and bilateral AI (BAI). Methods: We evaluated 152 patients, 105 (69.1%) with UAI and 47 (30.9%) with BAI. SH was diagnosed in the presence of serum cortisol levels after 1 mg dexamethasone suppression test (DST) or after 2-day low-dose DST (LDDST) > 50 nmol/L with at least one of the following parameters: midnight serum cortisol > 208 nmol/L, 24-h urinary free cortisol > 245 nmol/24 h, or ACTH < 10 ng/L. Bone mineral density (BMD) was measured at lumbar spine (LS) and femoral neck (FN). Results: Age, BMI, and waist circumference were comparable, and diabetes, hypertension and dyslipidemia occurred with similar frequency in both groups. The overall prevalence of SH was 20.5% based on post-1 mg DST, and 20.0% based on post-LDDST cortisol levels, and it was more prevalent in BAI than UAI patients (31.1% vs 15.2%, respectively, p=0.026). LS BMD was lower in BAI than in UAI patients (0.96±0.14 vs 0.87±0.15, p=0.002). There were no differences in FN BMD. The prevalence of osteoporosis was higher in BAI compared to UAI patients (37.1% vs 15.9%, respectively, p=0.011). Conclusions: Patients with BAI had higher prevalence of SH and osteoporosis than those with UAI. Frequency of other co-morbidities was similar. This may be due to the higher degree of autonomous cortisol secretion or different tissue-specific sensitivity to glucocorticoids. © 2016 Sanja Ognjanović et al.