ACTA ENDOCRINOLOGICA (BUC)

Context. Insulin resistance has been detected in a majority of patients with polycystic ovary syndrome (PCOS). Elevated neprilysin levels are associated with insulin resistance. Objective. The present study aims to investigate plasma neprilysin and its relationship with endocrine and metabolic characteristics in patients with PCOS. Subjects and Methods. Thirty-five premenopausal PCOS patients and 35 healthy volunteers of similar age were included in the study. Demographic characteristics, biochemical and hormonal findings and also plasma neprilysin levels were determined in these patients and healthy controls. Results. In our study, HOMA-IR values were significantly higher in PCOS patients (3.3 ± 1.8) compared with the controls [(1.6 ± 1), p<0.01]. Plasma neprilysin levels were significantly higher in the PCOS group compared to the control group (1502.1 ± 1641.2 vs. 764.6 ± 562.6 pg/ mL). There was no difference in plasma neprilysin levels when PCOS patients were classified as overweight-obesity (BMI≥25kg/m2) or non-obesity (BMI<25kg/m2). Conclusion. Our findings revealed significantly higher levels for plasma neprilysin and HOMA-IR values in PCOS patients when compared to controls. No significant differences were noted between obese PCOS patients and non-obese PCOS patients in terms of plasma neprilysin levels.

In acromegalic patients growth hormone (GH) excess induces insulin resistance (IR) but whether this is sufficient for pre-diabetes to occur is a matter of debate.\r\nAim. To assess the relative role of IR and insulin secretion in the pre-diabetes of acromegaly.\r\nMethods. 126 patients with acromegaly (79 women, 47 men) were included. Plasma glucose, GH and insulin levels were measured basal and 30, 60 and 120 minutes during a 75 g oral glucose tolerance test (OGTT). Basal and stimulated IR was assessed by homeostasis model assessment (HOMA), insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI) derived from OGTT (OGTTISI) respectively. Basal and stimulated insulin secretion was assessed using HOMA-B% index and insulinogenic index (IGI), respectively. The local Ethic Committee approved the study.\r\nResults. There were 51 subjects with pre-diabetes and 75 subjects with normal glucose tolerance (NGT). Pre-diabetes group had a significantly higher HOMA-IR index (4.8?3.3 vs 2.5?1.6, p<0.001) and nadir GH in OGTT (9.4 (4.3, 22.2) vs. 4.8 (2.2, 14.5) ng/mL, p=0.02) than NGT group. HOMA-IR did not correlate with nadir GH serum level in pre-diabetes group (r =0.22, p=0.12) but correlated significantly in NGT group (r= 0.5, p<0.001). In contrast, the pre-diabetes group had a lower HOMA-B% index than NGT group (165.4?15.7 vs 228.5?29, p<0.001). HOMA-B% did not correlate with nadir GH in both groups. Unadjusted IGI did not differ between the two groups (0.40?0.07 vs. 0.48?0.05, p=0.34) but became statistically significant after adjusting for both basal IR (HOMA-IR) (0.31?0.06 vs. 0.54?0.05, p=0.01) and stimulated IR (OGTTISI) (0.30?0.06 vs. 0.54?0.05, p=0.005). There were no significant differences between pre-diabetes and NGT groups regarding age, duration of acromegaly and sex.\r\nConclusions. Our data suggest that reduced basal and stimulated insulin secretion express the failure of &#946;-cells adaptation to increased GH-induced-insulin resistance and is the pathogenic mechanism of pre-diabetes in acromegaly.

Content. Metabolically healthy obese (MHO) individuals are characterized by absence of metabolic syndrome. The role of autonomic nervous system in metabolic profile of obese subjects has not been sufficiently investigated. Objective. We analyzed heart rate variability (HRV) in MHO and metabolically unhealthy obese (MUO) premenopausal women. Design. In 42 women metabolic profile was defined as MHO and MUO. Subjects and Methods. For metabolic profile Wildman, IDF and HOMA-IR criteria were used. Autonomic nervous system activity was assessed by analysis of heart rate variability. Results. There was no significant difference in HRV between MHO and MUO premenopausal women. In Wildman division, after adjustment for systolic blood pressure, RRNN and LF/HF were statistically different between groups (p=0.0001; p=0.029). In IDF division, adjusting for waist circumference, LF was significantly different between groups (p=0.004). In HOMA division, adjusting for HOMA, groups were different in SDNN (p=0.009), RMSSD (p=0.002), pNN50 (p=0.003), HF(p=0.002) and TP (p=0.005). Conclusions. Autonomic nervous system does not share the leading role in premenopausal women metabolic profile. The differences in HRV between MHO and MUO women depend on the metabolic health criteria. Systolic blood pressure, HOMA and waist circumference have significant effect on HRV differences between MHO and MUO premenopausal women.

Diabetes mellitus is associated with impairment of testicular functions.\r\nAim. The present study aimed to investigate the effects of ethyl pyruvate (EP) on the testicular tissue damage in rats\r\nwith streptozotocin (STZ)-induced diabetes.\r\nSubjects and methods. Thirty-two Wistar albino male rats were assigned into four equal groups as follows: (1) control\r\ngroup (n:8); (2) EP-treated non-diabetic group (n:8); (3) diabetic group (n:8); and (4) EP-treated diabetic group (n:8). Rats with STZ-induced diabetes were kept alive for 14\r\nweeks. After that, the EP solution was administered intraperitoneally to the rats in the EP-treated non-diabetic and diabetic groups at the dose of 50 mg/kg twice daily\r\nfor 14 days. At the end of this period, the left testes were removed from the rats for malondialdehyde (MDA) analysis, and the right testes were removed for histological\r\nexamination.\r\nResults. As compared with the control group, the diabetic group had elevated MDA levels (210.9?12.7) and increased\r\nthickness of the basement membrane of the seminiferous tubules (3.01?0.16), but decreased tubular diameter (159?9.0) and Johnsen?s score (5.31?0.1). In the EPtreated\r\ndiabetic group, diabetes-induced impairment was significantly improved.\r\nConclusion. These findings indicate that EP shows protective effects against diabetes-induced testicular dysfunction.

Background. Recent studies suggested that MPTP could cause gastrointestinal motility deficits additionally to its nonconclusive and controverted effects on the CNS (behavior and brain oxidative stress) in rats. A possible interaction between MPTP typical impairments and magnesium modulatory potential was previously suggested, as magnesium role was described in neuroprotection, gastrointestinal function, and oxidative stress. Aim. To investigate the possible modulatory effect of several magnesium intake formulations (via drinking water) in MPTP neurotoxicity and functional gastrointestinal impairment induction. Materials and Methods. Adult male Wistar rats were subjected to 3-week magnesium intake-controlled diets (magnesium depleted food and magnesium enriched drinking water) previously to acute subcutaneous MPTP treatment (30 mg/ kg body weight). Gastrointestinal motility (one hour stool collection test), and behavioral patterns (Y maze task, elevated plus maze test, open field test, forced swim test) were evaluated. Followingly, brain and bowel samples were collected, and oxidative stress was evaluated (glutathione peroxidase activity, malondial-dehyde concentrations). Results. MPTP could lead to magnesium intakedependent constipation-like gastrointestinal motility impairments, anxiety- and depressive-like affective behavior changes, and mild pain tolerance defects. Also, we found similar brain and intestinal patterns in magnesium-dependent oxidative stress. Conclusion. While the MPTP effects in normal magnesium intake could be regarded as not fully relevant in rat models and limited to the current experimental conditions, the abnormalities observed in the affective behavior, gastrointestinal status, pain tolerance, peripheric and central oxidative status could be indicative of the extent of the systemic effects of MPTP that are not restricted to the CNS level, but also to gastro-intestinal system.

Context. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel biomarker for cardiovascular diseases (CVD) risk estimation with high specificity for vascular inflammation. Few studies have investigated Lp-PLA2 levels in patients with metabolic syndrome (MetS) and obstructive sleep apnea syndrome (OSAS). Objective. This study aimed to evaluate the role of Lp-PLA2 levels as a marker of vascular inflammation that contributes to cardiometabolic dysfunction in patients with MetS and OSAS. Design. This is a prospective case-control study. Subjects and Methods. 83 men were enrolled. Following anthropometric measurements, laboratory analysis and overnight sleep study, patients were divided into three groups: MetS, OSAS with/without MetS. Serum Lp-PLA2 levels were determined by ELISA method. Results. Serum Lp-PLA2 levels were statistically significant among the three groups and were higher in OSAS with MetS group than those without MetS. A significant positive relationship between increased Lp-PLA2 level and CRP (C-reactive protein) and apnea–hypopnea index (AHI) was found. Average oxygen saturation (AvO2) and the lowest oxygen saturation were negatively correlated with Lp-PLA2. The number of desaturation events, oxygen desaturation index, AvO2, AHI and CRP were significant predictors of Lp-PLA2. Conclusions. Lp-PLA2 levels are associated with OSAS severity and might play an important role in predicting CVD in OSAS with/without MetS

Objective. Metabolic syndrome (MetS) is a metabolic condition with high prevalence worldwide. This study aims to examine the relationship between serum concentrations of gastrointestinal hormones such as cholecystokinin (CCK), ghrelin, peptide YY (PYY), and high sensitive C-reactive protein (hs-CRP) and the ingredients of MetS in obese population. Subjects and Methods. This case-control study included 40 obese subjects (20 with MetS and 20 BMI and age-matched control individuals). The age range of the participants was 20-50 years and the participants’ anthropometric characteristics were measured. Serum lipids and the concentrations of oxidized low density lipoprotein (Ox-LDL), insulin, hs-CRP, CCK, PYY, and ghrelin were assessed with commercial ELISA kits. Results. Serum levels of hs-CRP, total cholesterol (TC) and triglycerides (TG) in patients with MetS were significantly higher while CCK and insulin concentrations were higher in obese non- MetS group (P <0.05). PYY had a negative association with waist circumference (WC) and high density lipoprotein cholesterol (HDL-C) and ghrelin had a positive association with systolic blood pressure (SBP) and TC in obese control group (P < 0.05). In obese patients with MetS, hs-CRP had a strong positive association with TG. Conclusion. The current study revealed the possible role of hs-CRP and several GI- hormones in the pathogenesis of obesity-associated diseases and MetS. Additional works are needed to elucidate the possible underlying mechanisms and clarify several controversies in this issue.

Background. Fine-needle aspiration biopsy (FNAB) is the most accurate diagnostic method to assess the malignancy risk of thyroid nodules. However, nondiagnostic results may delay diagnosis, cause unnecessary interventions, and distress patients. Aim. We aimed to determine whether a correlation exists between patients’ situational anxiety, pain perception and non-diagnostic cytology results. Methods. The prospective study included patients who underwent thyroid FNAB at the Endocrinology Clinic of Sultan Abdulhamid Training and Research Hospital between 11/2022 and 02/2023. The State-Trait Anxiety Inventory (STAI) questionnaire and visual analogue scale (VAS) assessed situational anxiety and pain in patients undergoing biopsy procedures. We evaluated whether the STAI-S and VAS score is related to non-diagnostic results. Results. Of the 119 patients included in the study, 98 were female, and 21 were male. 25 (21%) nodules were non-diagnostic. The patients' mean STAI-S score before the biopsy was 47.31±12.37, and the mean VAS score after the thyroid biopsy was 2.57±1.51. A statistically significant relation was found between the patient's STAI-S score and VAS score and the cytology result of non-diagnostic (p= 0.001 and p=0.008). In univariate logistic regression, high pre-procedural anxiety (OR:3.09, 95% CI:1.07-8.94, P =0.037) and VAS score (OR:1.57, 95% CI: 1.17-2.10, P =0.002) were associated with non-diagnostic cytology. In multivariate logistic regression analysis, VAS score (OR: 1.59, 95% CI: 1.07-2.34, p=0.019) was still an independent factor related to specimen adequacy. Conclusions. Anxiety level and pain perception during FNAB may be considered risk factors for nondiagnostic cytology. Thus, reducing anxiety and pain may decrease the incidence of non-diagnostic outcomes.

Purpose. In this study, we aimed to investigate the relationship between hypothyroidism and sterile inflammation in rat heart tissue. Methods. Groups; control group (fed with standard rat chow diet and tab water) and the hypothyroid group (fed with a standard rat chow diet and tap water containing 0.05% 6-n-propyl-2-thiouracil for 6-weeks). At the end of the experiment, histopathologic examination was performed. The T3, T4, TSH and myocardial malondialdehyde (MDA) measurements were performed with an ELISA kit. TUNEL assay was performed to demonstrate apoptosis. Sterile inflammation markers, caspase-1 and NLRP3, were investigated by immunohistochemistry and western blot. Results. In histopathological examination, we observed leukocyte infiltration, myocardial atrophy, pyknotic nucleated cells and cytoplasmic vacuolization in hypothyroid group whereas the control group showed normal structure. MDA levels in myocardial tissue were significantly high in hypothyroid group when compared to the control group (P<0.05). Myocardial apoptosis increased in hypothyroid group when compared to the control group. NLRP3 and caspase-1 immunoreactivity was higher in the hypothyroid group. In ELISA results, we found significantly higher level of TSH and lower levels of T3 and T4 in hypothyroid group when compared to the control group. Conclusion. Hypothyroidism increased oxidative stress, and caused inflammatory alterations in cardiac tissue. In addition, our study also suggested that thyroid hormone deficiency would increase the amounts of cardiac NLRP3 and caspase-1 protein, which indicates that hypothyroidism exerts its destructive effects through sterile inflammation. Elucidation of sterile inflammation-associated pathways may produce promising results in the treatment of hypothyroidism-induced cardiac damage.

Background. Early prediction of anticancer therapy cardiotoxicity is essential for applying proper preventive and supporting therapeutic strategies. Objective. To evaluate plasma N-terminal fragment of pro-brain natriuretic peptide(NT-proBNP) related to cardiac dysfunction assessed by transthoracic 2 D echocardiography (2D-TTE) in patients with cancer and early onset asymptomatic anthracycline-induced cardiomyopathy(AIC). Methods. Prospective study of 68 patients with cancer treated with anthracyclines, followed up for 6 months. Diagnosis of AIC was set at 6 months by decreasing of left ventricular ejection fraction(LVEF) below 50% or with more than 10 units or 20% from baseline. NT-proBNP and 2D-TTE were assessed at enrollment, and thereafter at 3 and 6 months. Results. Fifteen(22.1%) patients developed AIC at 6 months of anthracycline treatment (group 1), and 53(77.95%) patients did not evolve with AIC (group 2). At 3 months, in patients from group 1 NT pro-BNP was significantly higher compared to group 2 [121.0 (119.8;140.8) pg/mL vs. 97.7(75.5;111.7) pg/mL, P=0.0001, values expressed as median (25th; 75th percentiles)]. Left ventricular(LV) diastolic dysfunction was significantly more frequent in group 1(93.3%) vs. group 2(37.7%), P=0.0002. NT-proBNP at 3 months proved accurate in predicting asymptomatic AIC at 6 months [area under the receiver operating characteristic curve(AUC)=0.845, 95%Confidence Interval(CI): 0.735-0.954, P=0.0001]. Newinstalled diastolic dysfunction at 3 months had a sensitivity of 60 %, a specificity of 77% in predicting AIC at 6 months. NT-proBNP assessed at 3 months above a cut-off=118.5pg/ mL was an independent predictor of AIC at 6 months. Conclusions. Plasma NT-proBNP at 3 months of anthracycline therapy proved to be an early independent predictor of asymptomatic anthracycline-induced cardiomyopathy.