ACTA ENDOCRINOLOGICA (BUC)

Background. Although cardiovascular risk is increased in patients with subclinical hypothyroidism (SCH), replacement therapy is not recommended in those with TSH levels\r\nbetween 5 and 10 mU/L.\r\nObjective. We aimed to evaluate the effects of levothyroxine (LT4) treatment on cardiovascular risk factors and carotid artery intima media thickness (CIMT) in patients with SCH who had TSH levels between 5 and 10 mU/L.\r\nSubjects and Methods. Sixty SCH patients with TSH levels between 5 and 10 mU/L were included in the study. Patients\r\nwere randomized into two groups as treatment (n=30) and control (n=30) groups. BMI, blood pressure, lipid profile, fibrinogen, homocysteine, hs-CRP and CIMT were measured in all patients at baseline and after six months. LT4 treatment was initiated and the dose was tapered according to TSH levels in treatment.\r\nResults. There was no significant difference between baseline and six month measurements in the control group. However, TSH, LDL-C, fibrinogen and mean CIMT measurements were decreased and HDL-C level was increased in the treatment group.\r\nConclusions. We suggest that LT4 therapy is necessary for the prevention of modifiable cardiovascular risk factors in\r\npatients with TSH levels between 5 and 10 mU/L.

Dual X-ray absorptiometry (DXA) is well known as the “gold standard” technique for the diagnosis of osteoporosis; therefore its “brightness” puts into shadow other valuable applications both in research and clinical practice. Whole body scan offers the opportunity to analyze the body composition, the oldest non bone densitometric application with valuable research data relevant for sarcopenia diagnosis, obesity and lipodystrophy diagnosis. Hip geometry analysis is also an older feature of DXA femur scan remained in the research area. The trabecular bone score (TBS) is the newest and most astonishing application using DXA scans: it brings bone quality data based on the image texture analysis of the spine DXA images with relevant impact on the fracture risk assessment independent of the bone density. Vertebral fracture assessment could be done in the same visit with bone densitometry using DXA rapid lateral spine scan: it is a borrowed application from plain radiology, as atypical femoral fracture (AFF) diagnosis and relies on the increased image quality of the DXA scans on recent equipments. At the same time, incidental findings on these images offer the opportunity to evaluate aortic calcifications useful for cardiovascular risk evaluation.

Background. The study included 505 patients, including 190 healthy controls, 166 euthyroid Hashimoto's thyroiditis (HT), 91 hypothyroid HT, and 58 nonimmunogenic hypothyroidism (NIH) patients. The records of the patients in each group were reviewed retrospectively. Objectives. The objective of this study was to evaluate the Systemic Inflammation Index (SII), Platelet to Lymphocyte Ratio (PLR), and Neutrophil to Lymphocyte Ratio (NLR) in HT and NIH, as well as their diagnostic value to predict the presence of inflammation. Results. In terms of SII, there was a significant difference between the control and patient groups (p<0.001). PLR and NLR values were also found to be significantly higher in the patient group (p<0.001 and p=0.007, respectively). When euthyroid HT, hypothyroid HT, and NIH subgroups were compared to the control group, there was a significant difference in SII, PLR (for all p<0.001), but not in NLR (p=0.059). SII, PLR, and NLR were not different between the subgroups (p=0.595, p=0.861, and p=0.777, respectively). Conclusion. It was found that the PLR, NLR, and SII indices were higher in Hashimoto’s thyroiditis and non-immunogenic hypothyroidism. Of these indices, SII was the most powerful marker to predict the presence of inflammation.

Purpose. The formation and accumulation of advanced glycation end products (AGEs) are enhanced with increased oxidative stress and inflammatory conditions. A hyperthyroid and hypothyroid state is associated with oxidative stress. This study aimed to evaluate skin AGE deposition, serum carboxymethyl-lysine (CML), and serum soluble receptor for AGEs (sRAGE) levels in hypothyroid and hyperthyroid patients. Methods. A total of 203 subjects were included in this cross-sectional study. After excluding diabetes mellitus, 103 newly diagnosed hypothyroid patients, 50 newly diagnosed hyperthyroid patients, and 50 control (euthyroid) subjects were enrolled. All tests were done before beginning the appropriate treatment. Accumulated AGEs in the skin collagen were measured by skin autofluorescence (SAF) using an AGE Reader. Results. SAF measurements were 1.82 ± 0.04, 1.80 ± 0.40, and 1.63 ± 0.30 arbitrary units for the hypothyroid, hyperthyroid, and euthyroid groups, respectively (p = 0.04). Serum CML levels were 8.2 ± 2.8, 10.2 ± 2.0, and 8.0 ± 3.3 ng/mL for the hypothyroid, hyperthyroid, and euthyroid groups, respectively (p = 0.01). sRAGE levels were similar between the groups. Serum thyroid-stimulating hormone and SAF measurements were positively correlated (r = 0.25, p = 0.02) in the hypothyroid group and negatively correlated in the hyperthyroid group (r = -0.36, p = 0.04). There was no correlation between CML and sRAGE levels. Conclusion. SAF measurements are increased in both hypo- and hyperthyroid normoglycemic patients. Serum CML levels are increased in hyperthyroid patients. Hypo and hyperthyroid states might be associated with acceleration of AGE accumulation and may have a long term effect on metabolic memory.

Background. We aimed to evaluate whether a high carbohydrate or a high fat diet differs in alteration of the inflammatory and metabolic risk factors in cardio-renal metabolic syndrome in rats. Methods. Twelve male Wister rats were randomly divided into two groups: one received diet 1 standard pellet rat diet (D1) containing 10% fat, 50% carbohydrate, 25% protein and another group received diet 2 (D2) containing 59% fat, 30% carbohydrate and 11% protein for 16 weeks. Weight was recorded weekly. FSG and insulin levels were measured using an enzymatic spectrophotometric and a standard ELISA kit respectively. Inflammatory parameters including TGF-β, MCP-1, TNF-α, IL-1β, IL-6 in the renal and cardiac tissues of rats were evaluated by ELISA technique. Result. Food intake in D1 and D2 groups increased in the study period, however food intake in D2 group was significantly higher compared with D1 group. FSG, HOMA and TG concentrations in D2 group were significantly higher compared to D1 group. Moreover, TGF-β and MCP- 1 concentrations in the renal tissues of D2 group and TNF-α in the cardiac tissues of D1 group were significantly higher compared with D1 group (P<0.05). Positive associations between IL-1β and TG and between HOMA, FSG with TGF-β and MCP-1 in the renal tissue of animals were also identified.

Background. Saturated free fatty acids, such as palmitate, can cause pancreatic β-cell apoptosis. Although the toxicity of palmitate could be mediated partly through endoplasmic reticulum (ER) stress, the mechanism by which fatty acid over-accumulation led to lipoapoptosis in β-cells has not been fully understood. Recently, the fat mass and obesity associated (FTO) gene is proved to be related to obesity and type 2 diabetes, but its function in β-cells remains largely unknown. Whether or not FTO could counteract palmitate induced β-cell apoptosis remains to be investigated. Methods. INS-1 cells were infected with FTO expression adenovirus and incubated with palmitate. Then, viability and induction of apoptosis were measured by MTT assay and Hoechst-staining, respectively. Western blot analyses were performed for unfolded protein response specific proteins and mRNA expression of target molecules was determined by real time-PCR. Results. Palmitate incubation led to β-cell apoptosis, whereas adenovirus-mediated FTO overexpression significantly ameliorated the effect of palmitate. Increased activation of X-box binding protein 1 (Xbp1) mRNA and phosphorylation of eIF2α were also observed after palmitate treatment, whereas FTO overexpression significantly ameliorated the effect of palmitate. The proapoptotic transcription factor CHOP was significantly enhanced by palmitate incubation. In contrast, in accordance with sustained cell survival, FTO overexpression resulted in notably decreased CHOP levels. Interestingly, mRNA expression of the chaperones Pdi, Calnexin and Grp94 was not altered by palmitate treatment, while FTO overexpression notably increased the expression of Bip. Conclusion. Our data showed that FTO overexpression could protect β-cells from palmitate-induced apoptosis partly through suppression of ER stress.

Context. Some adrenal tumors, such as pheochromocytoma, can be life-threatening. Therefore it is crucial to distinguish them from other lesions, especially prior to surgery. Chromogranin A (CgA) seems to potentially be a good marker for tumors of chromaffin origin. Objective. To assess the differentiating value of CgA in the diagnostic work-up of pheochromocytoma. Design. Retrospective study of operated patients with adrenal incidentaloma with lesions > 10 Hounsfield’s units (HU) on CT. Subjects and Methods. Thirty patients (11 males, 19 females; aged 61.5±21 years) were enrolled in the study. Patients using medications interfering with the assessment of CgA and metanephrines were excluded. Two groups were formed: those with pheochromocytoma (Ph, n=16) and those with non-pheochromocytoma (N-Ph, n=14) lesions. Data included radiological features of masses, serum CgA and 24-hour urine metanephrines (24 - HUM) concentrations. Results. No difference in 24-HUM level nor tumor size or density was found between groups Ph and N-Ph. Median serum CgA concentration was higher in Ph group compared to the N-Ph: 99.35 (68.12-172.73) vs. 52.92 (34.37-101.26) ng/mL, respectively (P=0.04). In Ph group, the size of the lesion correlated negatively with density (r= -0.53, P=0.042). No significant correlation in CgA, 24-HUM, density or size of the lesion was found. Performed curve receiver operating characteristic (ROC) showed AUC=0.7232 for CgA. Taking into account CgA serum value of ≤ 50 ng/mL (sensitivity: 93.75%, specificity: 50.00%, P=0.012), we proposed an algorithm for management of lesions > 10 HU on CT. Conclusion. CgA level ≤ 50 ng/mL might be useful in initial screening evidence for the exclusion of pheochromocytoma. It is crucial to eliminate factors interfering with the measurements.

Nodular thyroid disease (NTD) is represented by palpable thyroid nodules (solitary, multiple) and thyroid incidentalomas (identified by means of thyroid ultrasonography). The discussed entities carry the same risk of malignancy (about 5 %). The main objective in evaluating NTD is represented by the exclusion of malignancy by means of corroborated investigations, focused on the value of a panel of IHC markers.\r\nMaterial and methods. We included in the study 27 cases of NTD, evaluated by means of: clinical investigation, ultrasonography of the thyroid, cytological examination, morphological analysis and IHC. The used panel of IHC markers comprised: Ki-67, PCNA, CK 19 and c-erbB2 (DAKO LSAB method)\r\nResults. From the total of cases, 8 presented positivity with Ki-67 and 17 with PCNA. Regarding CK 19, the majority of PTC cases stained ++ and diffusely, but not papillary hyperplasia (focal positivity).c-erbB2 diffuse and intense positivity (+++) was noticed in PTC.The case with a follicular tumor of uncertain malignant potential stained weakly only with c-erbB2.\r\nConclusions. From the used panel of IHC markers, CK 19 presented the best value, being able to differentiate FVPTC from FTC and PTC from papillary hyperplasia.

Various clinical and experimental studies indicate that gonadal hormones exert\r\nmodulatory effects on nociception and analgesia.\r\nThe aim of the present study was to investigate the role of gonadal hormones in the\r\nresponse by male and female rats to thermal nociceptive stimulation.\r\nMaterials and Methods. 7 week old albino (Wistar) rats were used in our study.\r\nAnimals were randomly divided into control, sham and ovariectomised or orchidectomised\r\ngroups. Thermal pain threshold was measured through tail immersion test before and 10, 20\r\nor 40 days after gonadectomy. The pain threshold was measured as the time required to elicit\r\na flick of the tail called analgesia time. Serum testosterone, estradiol, progesterone or\r\nprolactin levels were measured simultaneously.\r\nThe results showed that analgesia time was higher in female (5.11 min) than in male\r\n(4.93 min) intact animals (p<0.05) indicating sex difference in response to thermal\r\nnociception. Serum testosterone, estradiol or progesterone level as well as analgesia time\r\nwere not significantly reduced 10 days after gondectomy. In male animals, analgesia time\r\nwas significantly decreased (p<0.01) 20 or 40 days after orchidectomy (2.25 or 2.14 min,\r\nrespectively) compared with control rats (4.93 min). Serum testosterone concentration was\r\nsignificantly reduced (p<0.05) 20 or 40 days after orchidectomy (0.08 or 0.09 ng/mL,\r\nrespectively) compared with control serum testosterone level (2.14 ng/mL). In female rats,\r\nanalgesia time was significantly decreased (p<0.001) 20 or 40 days after ovariectomy (2.87\r\nor 2.66 min, respectively) compared with control rats (5.11 min). Serum estradiol\r\nconcentration was significantly reduced (p<0.001) 20 or 40 days after ovariectomy (3.17 or\r\n0.87 ng/mL, respectively) compared with control serum estradiol level (19.95 ng/ml). Serum\r\nprogesterone level was also decreased (p<0.001) 20 or 40 days after orchidectomy (5.27 or\r\n0.55 ng/mL, respectively) compared with control serum estradiol level (17.66 ng/mL).\r\nSerum prolactin level was not significantly enhanced during experiment indicating that there\r\nwas not heat stress influencing the procedure.\r\nConclusively, our findings clearly indicate that depletion of gonadal hormones 20 or 40 days\r\nafter gonadectomy modulates the pain-induced behavioral responses related to thermal nociception.