ACTA ENDOCRINOLOGICA (BUC)

Objectives. Turner Syndrome (TS) is associated with a high risk of cardiac anomalies and cardiovascular disease. We aimed to evaluate patients with TS (n=33) for cardiac and aortic pathology using thorax magnetic resonance angiography (MRA). Subjects and methods. Clinical findings, karyotypes, echocardiogram (ECHO) findings and thorax MRA results were evaluated. Aortic dimensions were measured and standard Z scores of aortic diameters along with aortic size index (ASI) were calculated. Results. Mean age of the patients was 13.7±3.4 years. MRA revealed cardiovascular pathology in 10 patients (30%). CoA (n=4), aberrant right subclavian artery (n=3), dilatation of the ascending aorta (n=1), tortuosity of the descending aorta (n=1) and fusiform dilatation of the left subclavian artery (n=1) were found. Two of the four patients with CoA found on MRA were detected with ECHO. Mean diameter of the sinotubular junction was found to be elevated [mean±SD: 2.4±1.5]. Z scores for the diameters of the isthmus, ascending aorta and descending aorta were in normal ranges. 45,X patients were found to have significantly higher ASI values than non 45,X patients (p=0.036). Conclusion. Our findings indicate that patients with TS should be evaluated with MR imaging studies in addition to ECHO to reveal additional subtle cardiac and vascular anomalies. CoA which is very distally located or which has mild nature may not be seen by ECHO. The increase in ASI observed in 45,X patients may herald the development of life-threatening complications. Therefore, frequent followup is warranted in these patients.

About 250 patients with acquired partial lipodystrophy (Barraquer-Simons) syndrome have been reported so far. It is characterized by the loss of adipose tissue from the face and upper extremities, and accumulated fat in the rest of the body. The disease usually starts in females during childhood or adolescence, and usually after a febrile illness. Fat loss often comes into view in months or years. We present a 23-year-old female patient with acquired partial lipodystrophy , which is rarely seen.

Background. Thyroid hormone participates in lipid metabolism regulation. However, the effects on triacyleride or triacylglycerol metabolism are complex and not fully clarified yet. In this study, we try to identify novel thyroid hormone-targeting lipogenic metabolic genes and analyze their molecular regulative mechanism. Method. Thirty-five promoters of twenty-nine human lipogenic regulative enzyme genes were constructed into pXP1 luciferase reporter plasmid (PFK2/FBP2-luc) and transfected into HeGP2 cells, respectively. Gene expression induced by triiodothyronine (T3) was detected by luciferase assay. The T3-activated gene promoter was then analyzed by sequence analysis, deletion and mutation, and electrophoretic mobility shift assay (EMSA). Results. After 10 nM T3 stimulation for 36 h, phosphogluconate dehydrogenase, malic enzyme, Glycerol- 3-phosphate acyltransferase (GPAT) 3, and 1-acylglycerol-3- phosphate O-acyltransferase (AGPAT) 2 were significantly activated, respectively. A AGGTCA-like-direct-repeat-4 consensus thyroid hormone response element (DR4-TRE)- like sequence was found in the GPAT3 promoter, which was then verified to be necessary for T3-induced GPAT3 activation by gene deletion and mutation analysis. EMSA further identified that T3-thyroid receptor (TR) α-retinoid-X receptor (RXR) complex directly bound on the GPAT3 promoter. Conclusion. Triiodothyronine could activate the GPAT3 through DR4-TRE-like sequence binding to participate in lipogenic regulation. AGPAT2 may be another thyroid hormone target enzyme.

Introduction. Menopause increases the risk of cardiovascular disease in women. The aims of the present study were to evaluate the effects of swimming training on cardiac histology and expression of miR-29 and IGF-1 in the ovariectomized rats. Materials and methods. Thirty female Wistar rats were divided into sham and ovariectomized groups: sedentary control (OVX) and trained with 8 weeks exercise (OVX.E). On 57th day, blood was collected and used for lipid profile measurement. In addition, heart tissue was analyzed by reverse transcription–polymerase chain reaction for IGF- 1 mRNA and miR-29, and studied for histopathological changes. Results. Ovariectomy significantly decreased miR- 29 and IGF-1 expression in the heart compared to sham animals group (p<0.05). Exercise training increased miR-29 and IGF- 1 expression in the trained rats and improved histology and lipid profile compared with OVX group (p<0.05). Conclusion. Estrogen deficiency could lead to cardiac fibrosis through deregulation miR-29 and IGF-1 expression. The findings of the current study suggests a protective effect of exercise on heart against fibrotic changes in ovariectomized rats and support a potential preventive value of exercise in improving cardiac function after menopause.

Background. Adiponectin, vaspin and leptin are only a few of these numerous adipocytokines. Little is known about the behavior of adipocytokines and how adipose tissue metabolism is affected in this Type 1 DM model. In this study we investigated the serum levels of adiponectin, leptin, vaspin in streptozotocin(STZ) induced diabetic rats. Material and methods. Twelve Spraque Dawley albino rats were included in the study. The animals were divided into two groups. The first group was diabetic (D) (n: 6) and 60mg / kg STZ was administered intraperitoneally (i.p.) to these rats. The second group was the non-diabetic control (ND) group (n: 6). All the animals were euthanized by cervical dislocation. Quantification of vaspin, Adiponectin, leptin in serum was performed using the ELISA kit. Results. Adiponectin, vaspin levels of diabetic group were found to be statistically lower than of control group (p<0.05). Leptin levels were significantly higher in the diabetic group (P<0.05). Conclusion. There is a need for new researches that can explain the relationship between Vaspin, Leptin and Adiponectin and Type 1 diabetes. New studies in this area will open new horizons for the identification of new biomarkers in the diagnosis and treatment of Type 1 diabetes.

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.

Purpose. To determine the effectiveness of the basal calcitonin (CTb) determination in the early postoperative period to predict the possible recurrence (persistence) of medullary thyroid cancer (MTC). Material and Methods. A retrospective study of the treatment results in 194 patients with MTC (148 (76.3%) primary – group 1 and 46 (23.8%) recurrent – group 2) according to the levels of CTb in the first week after surgery and one year later. All groups were analyzed by staging, the level of preoperative and postoperative basal calcitonin 5 days and 1 year after the primary surgery. Findings. Among all patients, women prevailed – 144 (74.2%), the average age was (48.7±15.2), the average follow-up period was 67.5 months. Basal calcitonin was studied in patients of all groups in the preoperative and serially in the postoperative periods: 5 days and 1 year after the most radical surgical volumes. To test the hypothesis about the possibility of using CTb indicators in the early postoperative period, the degree of compliance with normal calcitonin indicators (≤18 pg/mL) was assessed by observation groups 5 days and 1 year after surgery. Conclusions. 1. The CTb value 5 days after surgery is no less a reliable marker of the result of surgical treatment of MTC than the currently recommended CTb measurement 2-3 months after surgery. 2. The technique is applicable for both primary and reoperations used for recurrent forms of medullary thyroid cancer.

Phenylketonuria (PKU) is the most frequent inherited amino acid metabolic disorder, and it may also be treated by dietary means. The determination of phenylalanine (Phe) levels in the blood plasma is important not only in early diagnostic, but also in monitoring the treatment of PKU. Purpose. The aim of our work was to develop a simple, sensitive and highly accurate procedure to determine the plasma concentration of Phe. Procedure. The measurement of plasma Phe concentration involves two steps: a) separation of plasma (from the blood taken on heparin), isolation and preparation of a concentrated solution of amino acids (by ion-exchange column chromatography on Dowex-50X8 and evaporation of the eluate in vacuum at 40˚C), and b) determination of Phe concentration in the solution of amino acids by HPLC. This analysis was performed using a Dionex Ultimate 3000 instrument equipped with a Ultimate 3000 diode array detector (DAD). The values of Phe concentration in the plasma of several patients were calculated using a calibration curve made with standards of Phe (dilutions of a stock solution of 50 mg/ dL). The measurements in duplicate (plasma Phe) or a greater number of samples from the same concentration of standards of Phe showed extremely small sample to sample differences. Concentrations as low as 0.2 mg/dL could be determined. Conclusion. The whole procedure presented here is relatively simple, rather inexpensive, however very sensitive and highly accurate. Consequently, it is very adequate for confirming the diagnosis of PKU in patients with neonatal hyperphenylalaninemia, as well as for monitoring the plasma concentration of Phe in patients with PKU.

In response to increasing interest of the European Commission on large-scale\r\ngenotyping for complex diseases, including variability in ethnic minorities in\r\nEurope (HEALTH-2009-4.3.3-1), at the end of 2008 we composed the\r\nHAPLOGENDIS consortium with partners from Russia and European countries. A\r\nfirst program (SICA) was proposed in cooperation with Russian Federal Agency for\r\nScience and Innovation, focusing on comparative population genetics on diseases\r\naccompanied by insulin resistance. Beside the specificity in analyzing the human\r\ngenome with SNP (single nucleotide polymorphism) and defining haplotype\r\nstructure of genes, the program rises new hypotheses which directly link\r\ncolonization of Europe at the Neolithic period from Eastern Ukraine or Anatolia\r\nwith the development of agriculture and major dietary and life style changes that\r\nmay have an impact on the genome. Although there will be many occasions to\r\nreview both genetic and clinical detailed aspects, this short note will expose some\r\nunifying ideas that joint these partners.

Introduction. Symptoms related to hypersecretion of hormones in patients with pituitary adenomas do not always correlate with immunohistochemical staining results. Objective. To evaluate the relationship between the pituitary adenomas hormone immunoexpressions and endocrine presentations. Patients and methods. The clinical status and immunoexpression of 72 patients who underwent transsphenoidal surgery for pituitary adenomas were analyzed. Results. Macroadenomas were diagnosed in 51 cases (70.84%), while microadenomas were found in 21 cases (29.16%). The 72 adenoma specimens were divided into 22 monohormonal, 21 plurihormonal, 21 immunonegative and 8 unreliable specimens. The positive immunohistochemical staining results occurred as follows: prolactin and growth hormone 25% each, adrenocorticotropic hormone 13.89%, thyroid-stimulating hormone 5.56%, leuteinizing hormone and follicle-stimulating hormone 12.5%, glycoprotein hormone alpha-subunit 22.22%. Statistically significant relationships between the immunohistochemical presentation and the preoperative diagnosis were found for prolactin and hyperprolactinemia, growth hormone and acromegaly and adrenocorticotropic hormone and Cushing’s syndrome. Conclusions. The lack of full concordance between the clinical presentations and immunohistochemical staining was mainly a result of the presence of nonfunctioning adenomas, plurihormonal adenomas and unreliable specimens. The morphometric method introduced in this study, utilizing the immunoexpression index, provided a very precise evaluation of pituitary adenomas pathology.