ACTA ENDOCRINOLOGICA (BUC)

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Objectives. The aim of this study was to evaluate serum levels of interleukin (IL)-8 in pre- and postmenopausal women and in patients with surgically-induced menopause, and the relationship between IL-8 and vasomotor symptoms. Material and Method. 175 women were enrolled and were divided into 5 groups (I – Fertile women; II – Pre- and perimenopausal women; III – Postmenopausal women; IV – Surgically-induced menopause; V – Chronic inflammation). Multiplex cytokine kits were used to evaluate serum levels of interleukin-8. We determined the serum levels of the follicle stimulating hormone, of the luteinizing hormone, 17β-estradiol, progesterone, dehydroepiandrosterone and dehydroepiandrosterone sulfate using sandwich ELISA. The severity of the vasomotor symptoms was evaluated according to FDA guidelines. Results. Serum concentration of IL-8 in women with natural menopause (233.0±226.5 pg/ml; p<0.001) and in women with surgically-induced menopause (148.0±162.0 pg/ml; p=0.045) is significantly higher than in women of reproductive age (84.88±82.32 pg/ml). Serum levels of IL-8 in premenopausal women, postmenopausal women, and in women with surgically-induced menopause, respectively, with severe and moderate hot flashes, on one hand (174.8±90.94 pg/ml, 369.3±194.2 pg/ml, respectively 274.1±146.3 pg/ml), is significantly higher than in women without vasomotor symptoms or with mild hot flashes, on the other hand (19.97±22.15 pg/ml, 28.66±35.72 pg/ml, respectively 28.94±37.68 pg/ml; p<0.001). Serum levels of IL-8 are significantly higher in women of reproductive age with chronic inflammatory pathology (152.3±121.0 pg/ml) than in women without such pathology (84.88±82.32 pg/ml; p=0.02). Conclusions. IL-8 is significantly higher in postmenopausal women with vasomotor symptoms than in women without vasomotor symptoms. In the postmenopausal group, the serum levels of IL-8 are similar to those in women with chronic inflammatory pathology. IL-8 could be a key factor in occurrence of hot flashes in menopause and could be associated with peripheral vasodilatation in these women.

Objective: Thyroid development was studied mainly on animal models and data in humans are scarce. Knowing that there are interspecies differences and a specific timing of thyroid development we aimed to reveal intimate aspects of the human foetal morphology and function.\r\nMaterial and method: Thyroids from 20 aborted fetuses of different gestational ages (8-16 weeks) were embedded in paraffin, sectioned, coloured and immunohistochemically processed using the Avidin-Biotin Complex&#8211;Peroxidase (ABC) method with a pannel of antibodies aimed to reveal the secretory activity (antithyroglobulin monoclonal and polyclonal and anti TITF1 antibodies), the differentiation of intermediate filaments (anti AE1/AE3, anti CK7 and antivimentin monoclonal antibodies), of C cells (anti CEA monoclonal antibodies) and of the thyroid vascular net (anti CD34 monoclonal antibodies).\r\nResults: Thyroglobulin expression was present in thyrocytes cytoplasm even before follicles are formed (8-10 weeks); after 12 weeks appeared also within the colloid and expression increased after 14 weeks showing a luminal pattern of distribution similar to the mature thyroid. TITF1 was present in the thyrocytes nuclei of all groups, weak till 14 weeks and intense thereafter and in the C cells nuclei. C cells appeared after 10 weeks and expressed CEA, vimentin and CK7. Immunostaining for keratins (AE1/AE3, CK7) was rarely positive in cordonal thyrocytes, but was present in follicular thyrocytes and increased with gestational age. Some thyrocytes of all groups were vimentin positive and showed coexpression with cytokeratins. CD 34 expression indicated an early vascular differentiation being present in isolated endothelial cells before 10 weeks and structured capillaries after 10 weeks of gestational age.\r\nConclusions: Immunohistochemistry proved to be a useful tool in our attempt to shed light on human thyroid development which would permit a better pathogenic understanding of thyroid dysgenesias and thyroid neoplasms.

Context. Interventions that suppress hepatic gluconeogenesis from amino acids may be useful for improving glycemic control in diabetic patients. Objectives. It was shown that administration of glucocorticoid receptor antagonist Mifepristone (MIF) leads to variously pronounced changes in the alanine-, aspartate-, tyrosine- aminotransferases (ALT, AST, TAT) activity in the liver of experimental animals. It has been suggested that this selective effect of MIF may be related to differences in the expression of the corresponding genes. The aim of the study was to investigate the gene expression and activity of ALT, AST and TAT in the liver of rats with streptozotocin-related diabetes (StD) under the long-term oral MIF administration. Methods. Male Wistar rats (n=48) with StD under the 10-days oral MIF administration were used. It was measured the activity of ALT, AST, TAT enzymes and relative expression of this genes in the liver of experimental animals. Results. In rats with StD the gene expression of all three studied aminotransferases in the liver was statistically significantly increased and their activity was increased as well. MIF administration did not change the studied genes expression and enzymes activity to healthy rats and caused a decrease in expression of ALT and AST genes and activity of these enzymes to rats with StD. However, the expression of the TAT gene and the activity of this enzyme in the liver of rats with StD increased upon MIF administration in comparison with animals with StD. Conclusions. The introduction of MIF against the background of StD reduces the expression of genes and the activity of ALT and AST in the liver, what determine the transamination of amino acids to include them in gluconeogenesis, but increases the expression of genes and the activity of TAT, what determine the inclusion of tyrosine in the biogenic amines synthesis. The mechanisms of such selectivity require further study.

Background: Simultaneously determined plasma chromogranin A (CgA) and free metanephrines can substantially enrich laboratory diagnosis of pheochromocytoma (PHEO). CgA-like\r\nimmunoreactivity was discovered in saliva. Salivary CgA (CgA-LIS) could precise PHEO diagnosis in a non-aggressive\r\nmanner for the patient using saliva instead of plasma samples.\r\nSubjects and methods: A group of 10 PHEO patients: 7 women (22 to 72 years ) and 3 men (42 to 59 years) and a control\r\ngroup of 10 subjects were included in this retrospective study. Plasma free metanephrines and CgA were assayed by\r\nElisa kits. Salivary CgA was assayed by an EIA kit. Both analytical and diagnosis performance of the CgA-LIS vs. CgA were compared using Passing& Bablok regression and Receiver Operating Curves (ROC analysis).\r\nResults: In tumor group, mean values for all 4 assayed parameters were significantly increased in comparison with\r\nthe same parameters in normal group as expected: free plasma normetanephrines (NMNp) was: 2773 ? 704.57pg/mL versus 48.51 ? 9.87 pg/mL in controls; free plasma metanephrines (MNp) was: 864.4 ? 330.75 pg/mL versus 19.18 ? 3.69 pg/mL in normals; CgA was: 695.10?235.22 ng/mL versus 74.4?5.37 ng/mL in controls; CgALIS was: 17.62?6.79 pmol/L versus 0.94 ?\r\n0.20 pmol/L in normals. Passing & Bablok regression equation for CgA-LIS versus CgA was: Y=0.0181 + 0.0146X. Cusum test\r\nfor linearity revealed no significant deviation from linearity (P>0.10). A significant correlation between NMNp and CgA-LIS was established in all 20 subjects: r=0.82, P<0.0001. Pairwise comparison of ROC curves for both markers showed no significant difference between areas. Salivary CgA could be successfully used instead of plasma CgA in biochemical diagnosis of pheochromocytoma.\r\nConclusions: We can conclude that salivary CgA could be used as a nonstressfull marker for diagnosis purpose in pheochromocytoma.

Thyroid hormones play a crucial role in the regulation of the mitochondrial oxidative\r\nmetabolism. Hyperthyroidism caused by the acceleration of the energy metabolism leads to\r\nthe occurrence of cellular oxidative stress.\r\nThe aim is to evaluate the pro-oxidant / antioxidant balance and the effect of vitamin\r\nE supplementation in damage caused by the excessive administration of thyroid hormones.\r\nMaterials and Methods. White, male Wistar rats were used in the study. Thirty male\r\nWistar rats were divided into three groups (1:control group, 2:animals treated with LThyroxine\r\n10 &#956;g/animal/day for 30 days, 3:L-Thyroxin treated rats protected with vitamin\r\nE 10 mg/animal/day). Malondialdehyde (MDA), the marker of lipid peroxidation, carbonyl\r\nproteins, SH groups, glutathione (GSH) and superoxide dismutase (SOD) were determined\r\nfrom the serum, while MDA, carbonyl proteins, SH groups and GSH were determined from\r\nthe thyroid tissue homogenates.\r\nThe results showed increased levels of carbonyl proteins (1.31?0.33 nmol/mg protein,\r\np=0.0001) in serum in thyrotoxic group versus control, while MDA levels did not differ\r\nsignificantly from the control. Significantly low values of the SH groups, GSH and SOD were\r\nfound (p<0.001) in the plasma of Thyroxin treated rats. Vitamin E supplementation\r\nsignificantly increased plasma MDA levels in the Thyroxin treated group as compared with\r\nthe control group (p=0.01) and with the animals treated only with Thyroxin (p=0.04).\r\nCarbonyl protein levels in plasma of the hyperthyroid supplemented rats were also increased\r\nas compared to controls (p=0.0002). Antioxidant capacity markers in plasma of group 3 were\r\ndecreased compared with group 1. The marker of lipid peroxidation (MDA) significantly\r\ndecreased in thyroid homogenates of the group 2 as compared with group 1 (p=0.004).\r\nSignificantly high levels of the SH groups (p=0.0006) and low levels of GSH (p=0.0001) were\r\nfound in thyroid homogenates of the L-Thyroxin treated group as compared with controls.\r\nThese results suggest that experimental hyperthyroidism is accompanied with\r\nincreased oxidative stress and with the consumption of antioxidant enzymes in induced\r\noxidative aggressions. No protective effects of vitamin E on oxidative stress induced by\r\nexcessive administration of thyroid hormones were detected.

Leptin seems to play a significant role in the regulation of pituitary GH secretion. In GH deficient children serum leptin level is higher than in GH sufficient ones. Administration of rhGH resulted in a significant decrease in serum leptin in GH deficient but also in children displaying idiopathic growth delay, small for gestational age at birth, Prader-Willi syndrome and other obese. LBA is in fact the soluble form of leptin receptor. It was previously shown that GH deficient children are mostly hyperleptinemic and that GH induces a reduction in leptin level within 3 weeks of therapy. Such a reduction could serve as a valuable marker of the long term growth response. Twenty short children whose GH status was previously assessed through GH provocative tests and auxological evaluation were explored as concerns IGF I, leptin and LBA. According to these criteria they were classified as GH-deficient and GH-sufficient. Blood samples for the assay of serum leptin and LBA and IGF I were drawn at 8 a.m. A daily dose of 0.35 mg of rhGH was given subcutaneously at 8 pm in 12 of them and the same sampling was done 12 hours after the last injection. A therapy with GH with the same preparation and in comparable weekly dosage was started in all children and the height gain was evaluated after six months. Total serum leptin was assayed by a commercially available sandwich ELISA kit. LBA was assayed by a sandwich ELISA kit using a human IgG-Fc fragment of leptin receptor. IGF I determination was performed by the OCTEIA kit in a two-site immunoenzymometric assay (IEMA). The means and SEM before and after 10 days of GH administration in the whole group were of 3.4 ? 0.71 ng/ml and 1.7 ? 0.16 (p< 0.02) for leptin 0.27.1 ? 0.92 U/ml and 23.6 ?1.66 (ns) for LBA, 48.9 ? 10.65 ng/ml and 84.3 ? 17.61 for IGF I (p> 0.05, ns). Comparison between GH deficient (def) and GH sufficient (suf) subgroups resulted in significant differences as regards initial values for IGF I (20.2 ? 4.21 in def vs 77.6 ? 16.7 in suf, p< 0.02) but not in leptin, LBA, height and weight z scores. After ten days of therapy no significant differences were noted in subgroups for leptin, LBA and IGF I (absolute values), but a striking difference was noted in percentual rise of IGF I in def children. There was a significant positive correlation between leptin basal level and the growth rate in the subsequent 6 months of GH therapy. No similar correlation was noted for IGF I and LBA. It was concluded that hyperleptinemic GH deficient children seem to be particularly sensitive to the growth promoting effect of rhGH at least in the first six months of therapy.

Objective. Medical Nutrition Therapy (MNT) is important in the treatment and regulation of diabetic patients. In this study, it was aimed to evaluate the effects of medical nutrition therapy on Pentraxin-3, hsCRP and body composition analysis in Type 2 diabetes patients (DM). Methods. This study included 160 individuals who were admitted and diagnosed with Type 2 DM. Laboratory, clinical, anthropometric and body composition parameters were obtained 3 months after baseline evaluation of the patients and the MNT was given by the dietitian. Results. After 3 months MNT, weight, body mass index, waist circumference, body fat weight, body fat ratio and visceral fat area (p<0.001), glucose (p<0.001), insulin (p=0.033), HOMA index (p=0.004), HbA1c (p<0.001), total cholesterol (p=0.001), LDL (p=0.008), ALT (p<0.001) and hsCRP (p<0.001) levels were significantly lower than they were before MNT. There wasn’t significant difference in triglyceride (p=0.509), HDL (p=0.079), Pentraxin-3 (p=0.706) levels and waist-to-hip ratio (p=0.802). The level of Framingham risk score after MNT was significantly lower (p<0.001). Conclusion. In this study, it was cocluded that MNT, applied to patients with Type 2 DM decreased cardiovascular risk and inflammation, contributed to the maintenance of glycemic control, and a significantly improved the body composition.

Context. Follicular thyroid carcinomas (FTC) represent 6-10 % of all thyroid carcinomas; the evolution of FTC is quite controversial, partly due to frequent changes of the histopathological definition (minimally invasive–MIFTC or widely invasive carcinoma–WIFTC) and treatment strategies adjustments. Objective. This research aims to examine the diagnostic procedure, therapeutic attitude and survival rates of patients with FTC, over a period of 16 years in the same institution, with a follow-up of at least 4 years, by analyzing correlations between histology subtype, treatments and the rate of recurrent disease. Subjects and methods. We have studied 5891 patients with thyroid carcinomas who have undergone surgical or oncological treatment within the institution, between 1st January 2000 – 31st December 2015; among them we found 133 patients (2.25%) with “pure” follicular thyroid carcinoma: 114 (86%) women and 19 (14%) men, with a female-male ratio of 6:1. The age of the patients ranged from 10 to 76 years, with an average of 47.8 years. Statistical analysis was done comparing differences among groups of MIFTC and WIFTC. Results. There was an unexpected high percentage of WIFTC and also an increased number of biochemically persistent and/or recurrent disease in patients with MIFTC. A stronger correlation was observed with the tumour dimensions, rather than with the histopathological subtype. Conclusions. This research observed that overall survival was associated with tumour size rather than histopathological subtype and there is an important need to perform further studies to assess the effectiveness of treatment strategies.

Renal osteodystrophy and low bone mass are frequently found in patients with end-stage renal disease (ESRD). Our aim was to identify the independent predictors of age - and sex-adjusted bone mineral density (BMD), measured at different traditional sites, in patients with ESRD treated by hemodialysis (HD) or peritoneal dialysis (PD). Patients and Methods. We consecutively assessed 23 patients with ESRD (17 on HD and 6 on PD). Patients treated with 1,25 dihydroxyvitamin D, vitamin D derivates (paricalcitol) or calcimimetics were excluded. Serum parathormone and 25OH vitamin D were measured in all patients. In HD patients all biochemical measurements were done in the day between dialysis sesions. BMD was assessed at following sites: femoral neck, total proximal femur, 1/3 radius, ultradistal (UD) radius and total radius. Radial BMD was assessed in the forearm without arteriovenous fistula. BMD Z-score provided by the manufacturer was used. Results. In patiens undergoing PD the femoral neck BMD Z-score was significantly higher than in HD patients (difference -0.77 DS, 95% CI for difference -1.48 to -0.06). PTH correlated significantly with BMD Z-score at the 1/3 (r=-0.664, p<0.001) and total (r=-0.583, p=0.002) radius levels. Total proximal femur and UD radius BMD Z-scores did not correlate with any of the proposed variables. Years of dialysis, 25OH vitamin D and body mass index did not correlate with BMD Z-score at any site. Conclusion. In patients with ESRD PTH correlates strongly with BMD Z-score at cortical sites. PD seems to be less harmful to BMD than HD.