ACTA ENDOCRINOLOGICA (BUC)

Alzheimer’s disease(AD) is the leading cause of dementia and is characterized by the presence of extensive plaque deposition and neurofibrillary pathology. The aim of the present study was to make an update regarding the influence of estrogens and SERMs on inflammation and on the resolution of inflammation, respectively, focusing on these most important features implicated in the pathophysiology of AD. Several hypothesised mechanisms of action of estrogens and SERM are exposed and also some relevant clinical studies on this subject are analysed. The analyzed studies have a high heterogeneity of preparations used, of administration routes, of the female population included and of the periods of time from the appearance/ induction of menopause to the therapeutic intervention and also of follow-up periods of patients and of the means of evaluating their cognitive decline. One can say that all the ways of pharmacological influence on the membrane or intracellular signalling system associated to estrogens that may have clinical importance in the prevention and possibly in the treatment of AD have not been exhausted. Estrogens with selective ERα or G protein-coupled estrogen receptors (GPER1 or GqMER) effects could be used to influence the resolution of inflammation process, with positive effects on AD evolution.

The beta 3 agonists have antiobesity, thermogenetic and lipolytic properties. Starting from BRL35135 structure, a well-known beta 3 agonist, 3 new phenylethylamine derivates (A, B, C) and 2 new pyrazol derivates (D, E) were synthesized.\r\nPurpose. The aim of this study was to evaluate the effect of five new compounds derived from of BRL35135 on glycemia in normal and diabetic rats.\r\nMethods. For each experiment, test and control groups of 6, 8 or 10 male Wistar rats were used. For inducing experimental diabetes mellitus, alloxan (100 mg/kg body weight) was intravenously injected. Tested substances were intraperitoneally injected (1 or 100 mg/kg body weight) and glycemia values were measured before and at 3 hours after their administration. Control groups received propyleneglycol, the solvent of the new compounds. Glycemia values were measured with a calibrated glucometer.\r\nResults. In normal rats one of the phenylethylamine compounds (substance C) (100 mg/kg body weight) had a hypoglycemic effect comparative to control (p=0.03). In glucose tolerance test, substance E (100 mg/kg body weight) stopped the increase of glycemic values determined by glucose oral administration in the first 60 minutes comparative to control (p=0.03). In the alloxanic diabetes model, before insulin administration the substances hypoglycemic effect could not be measured with the glucometer because of very high values of glycemia. After insulin administration no significant differences between the treated and the control groups were registered. Further studies on the hypoglycemic effect of substances C and E are needed in order to establish their possible antidiabetic effect.\r\nConclusion. A phenylethylamine derivate and a pyrazol derivate of BRL35135 had a hypoglycemic effect in normal rats, but this effect could not be confirmed in rats with alloxanic diabetes.

Objective. Estrogen receptor alpha (ESR1) polymorphisms (XbaI and PvuII) and vitamin D receptor (VDR) polymorphisms (FokI, BsmI, ApaI and TaqI) are the most frequently studied regarding the correlations with the infertility in males, but the results are controversial. The purpose of this study is to evaluate possible correlations between hormonal markers, VDR and ESR1 genotypes and semen analysis, in order to bring new data for a better understanding of male infertility. Subjects and Methods. 42 infertile men and 28 controls were enrolled. The polymorphisms of VDR gene (ApaI, TaqI, BsmI and FokI) and ESR1 (XbaI and PvuII) were performed by PCR-RFLP, along with hormonal markers. Results. An important correlation between PvuII polymorphism and infertility status was revealed. A significant difference between control and infertility group regarding the presence of BsmI (A>G) and ApaI (G>T) polymorphisms was observed in infertile group, prolactin and DHEA were found to correlate significantly statistic with BsmI GG genotype, whereas ApaI AA genotype correlates with prolactin and SHBG levels. Conclusions. By a multivariate analysis, we demonstrated a cumulative effect of some genetic variants in the hormonal status of infertile patients. Therefore, we show that specific genetic variants of ESR1 and VDR genes may jointly influence human spermatogenesis.

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.

COST (European Cooperation in Science and Technology) is an intergovernmental organization established to fund research networks known as “COST Actions” across the sciences. COST enables break-through scientific developments leading to new concepts and products and thereby contributes to strengthen Europe’s research and innovation capacities. The Action BM1105 investigated the neuroendocrine mechanisms that are integrated at the hypothalamic level and regulate the complex organ network controlling reproduction. Through the development of a networking platform, the Action advanced the field of neuroendocrinology via: guidelines for the best clinical care of GnRH deficient patients, translating scientific understanding into improved patient care and creating a lasting European tradition of excellence in the field of reproductive medicine.

Context. Tumors associated with thyroid gland are relatively rare. Papillary thyroid cancer (PTC) represents the most\r\nfrequent thyroid neoplasm, and it has almost in all of the cases favorable prognosis. In the largest number of the cases, PTC remains within the thyroid gland or it gives the\r\nlymphogenic metastasis in the cervical lymph nodes and, extremely rare, it results in hematogenic metastasis.\r\nObjective. To present a case of a patient who had a distant secondary deposit in pelvic bone and sacral bone as a first sign of the PTC.\r\nSubjects and Methods. A 56 year old male was presented in this report.\r\nResults. After intensive hip pain, patient was diagnosed with osteolytic lesion in sacral and left pelvic bone. After aspiration biopsy, macroscopic analysis and imunohistochemistry, diagnosis of PTC was set. Patient has undergone total thyroidectomy, two doses of radioiodine\r\nwere applied and secondary deposit palliative radiotherapy as well.\r\nConclusions. The total thyroidectomy is the first line therapy in the PTC patients for primary tumors, while the therapy for the secondary deposits requires surgical\r\nprocedures combined with other means of treatment.

Introduction. Vitamin D (VD) levels were correlated with different health conditions, including reproductive disorders in males. Vitamin D action is mediated through vitamin D receptor (VDR), which acts as a transcription factor. VDR gene promoter is embedded in a GC-rich island. The VDR gene has been shown to have several polymorphisms that affect the receptor function. Aim. To examine the relationship between Cdx- 2 polymorphism (rs17883968), the methylation status of VDR’s promoter and serum levels of 25-hydroxyvitamin D in male infertility. Patients and Methods. A total of 69 infertile men and 37 age-matched controls were enrolled in this study. Vitamin D level assessments were detected using the electrochemiluminescent method. Cdx-2 VDR polymorphism identification was performed by PCR on DNA samples from blood, followed by restriction. Methylation of VDR gene promoter was assessed by qMS-PCR using bisulfite-treated DNA from fresh sperm. Results. Vitamin D levels was found to be significantly decreased in infertile groups compared the controls (p=0.0279). The GG genotype was found in a higher percentage in controls and the AA genotype was higher in infertile group (p=0.0056). Infertile homozygote (GG) and heterozygote (GA) individuals had significantly higher vitamin D levels than AA homozygote. Methylation is higher in individuals with lower vitamin D levels and AA genotype is characterized by higher methylation values. Conclusion. The results provide new insights of Cdx-2 polymorphism is involved in vitamin D deficiency, highlighting the important role of epigenetic modification of vitamin D receptor and male infertility along with the genetic context.

Background. Malignant melanoma is the most aggressive form of skin cancer with a rapidly increasing incidence rate. In contrast to other tumors, the role of sex steroid hormones\r\nin the initiation and progression of melanoma remains unclear.\r\nObjective. To assess the interaction between the content and composition of gangliosides and sex steroid hormones 17&#946;-\r\nestradiol (E2) and testosterone (T) in malignant melanoma.\r\nPatients and methods. The analysis included 45 melanoma patients (age 28-86; 14 men, 15 non -pregnant women in mid\r\nfollicular phase and 16 postmenopausal women) and 46 healthy controls. Serum levels of gangliosides (GM1-3, GD1a,b,2,3, GT1b, GQ1b), estradiol, testosterone measured in serum by chromatographic and immunochemiluminescence methods were correlated with sex and age.\r\nResults. Steroid hormones levels showed no differences between groups (p>0.05), while total gangliosides in normal\r\nserum were significantly lower than total ganglioside concentrations determined in melanoma samples (18.63 ? 3.17 mg/dL versus 74.82 ? 34.56 mg/dL) (p<0.05). There were no differences related to sex or age within groups regarding total gangliosides levels. Gangliosides pattern in\r\nmelanoma patients compared to control showed lower GM3, higher GD3, lower GM3/GD3 ratio, increased GD2 levels, and\r\nno significant variation of GM1, GM2, GD1a, GT1b gangliosides. There is a positive correlation between estradiol levels and total gangliosides concentration both in non-pregnant premenopausal and postmenopausal melanoma patients. GM3 is negatively correlated with estradiol levels in melanoma group, GT1b and O-Acetyl GD3 concentrations are positively correlated with estradiol levels in women with melanoma. Testosterone levels showed no significant\r\ncorrelation with the content and pattern of gangliosides in melanoma patients.\r\nConclusions. The correlations between content and composition of gangliosides and estradiol in melanoma suggest a possible role of these molecules in melanoma behavior.

Morris Syndrome is a pathological condition which needs a special approach regarding both diagnosis and treatment\r\nbecause of its rarity. While the diagnosis is based on karyotype test, the treatment should follow the idea of harmless and cosmetic benefits as well as complete gonads removal. This paper is presenting the usefulness and advantages of minimally invasive surgery as a feasible treatment for such a disease. A retrospective study was performed for two patients with Morris Syndrome, admitted to\r\nthe ?CI Parhon? National Institute of Endocrinology, Bucharest, Romania, followed-up for 4 - 16 years, and operated to the Department of Surgery, Emergency\r\nHospital, Bucharest, Romania. Patients with primary amenorrhea have been clinically observed and three patients\r\nwith 46, XY karyotype have been identified as Morris Syndrome cases needing surgical removal of the intraperitoneal gonads because of the risk of malignant transformation. A minimally invasive surgical technique has\r\nbeen chosen for proper treatment: the anterior transperitoneal laparoscopic approach. The surgery was adapted to every case, in according with preoperative imagistic diagnosis of the intraperitoneal testes\r\n(localization, dimensions, adjacent organs involvement, surgical access). No postoperative complications were noticed and specimens' pathology confirmed the final\r\ndiagnosis. Cosmetic benefits were achieved for every young patient as well as rapid postoperative recovery (discharge after 48 hours). The authors concluded that Morris Syndrome patients could benefit from the laparoscopic surgery which is a feasible, safe and proper treatment for such cases.

Background: Salivary monitoring of hormone levels has many advantages over the more conventional serum/plasma analysis. Salivary free metanephrines (MN) and normetanephrines (NMN) could precise biochemical diagnosis of pheochromocytoma (PHEO) as an alternative to plasma metabolites.\r\nSubjects and methods: The prospective case-control study included a group of 30 patients confirmed with PHEO an age-matched control group of 70 normotensive subjects. The PHEO diagnosis was suspected on clinical ground and confirmed by imaging studies and classical neuroendocrine markers. Free plasma and salivary NMN and MN were assayed using enzyme immunoassay for both metabolites.\r\nResults: In tumor cases all metabolites were increased. As expected, values for all 4 parameters (mean?SEM) differed significantly in tumor group vs. normal group: free plasma\r\nnormetanephrines (NMNp): 1514.16 ? 282.97 pg/mL vs 47.82?2.52 pg/mL; free salivary normetanephrines (NMNs):\r\n663.63?168.47 pg/mL vs 44.98? 2.47 pg/mL; free plasma metanephrines (MNp): 445.20 ? 99.92 pg/mL vs 18.87?1.03\r\npg/mL; free salivary metanephrines (MNs):206.60?91.48 pg/mL vs 14.47?0.72 pg/mL with significant correlations in all\r\n100 subjects. Passing & Bablok regression showed no significant deviation from linearity in Elisa assay of NMNs vs NMNp; a significant deviation from linearity existed\r\nin Elisa assay of MNs vs MNp. Cut-off values, sensitivity and specificity for all 4 parameters were calculated by ROC\r\nanalysis. Plasma and salivary normetanephrines proved similar sensitivity (100%) and specificity (100%). Pairwise\r\ncomparison of ROC curves areas showed no significant differences between NMNp vs NMNs and MNp vs MNs. Ten cases were investigated post-surgery. All 4 parameters\r\nshowed no significant differences vs. control group.\r\nConclusions: Salivary free normetanephrines could be used as a nonstressful marker for diagnosis purpose in pheochromocytoma proving similar sensitivity and specificity as plasma free normetanephrines.