ACTA ENDOCRINOLOGICA (BUC)

Background. The modern management of phenylketonuria (PKU) consists of generalized newborn screening (NBS) for hyperphenylalaninemia (HPA), confirmation of HPA in children detected in the NBS, introduction of dietary treatment in the first weeks of life, followed by monitoring the treatment of PKU for decades to maintain phenylalaninemia within the limits that will not affect the brain. The present study aimed to evaluate the usefulness of two chromatographic methodologies for determination of plasma Phe level in the routine management of PKU: the two dimensional thin layer chromatography (2D - TLC) and the high performance liquid chromatography (HPLC) procedures, respectively. Material and Methods. Samples of blood from 23 children with HPA detected by neonatal screening or with confirmed PKU who received treatment by low-Phe diet were analyzed to estimate the plasma Phe level by the two chromatographic procedures. Results. In case of three subjects the very low concentrations of plasma Phe could not be detected by the 2D - TLC methodology, since the spot was not visible on the chromatogram. In four patients the differences between the values of plasma Phe determined by the two methodologies are not statistically significant, while in fifteen subjects the differences are highly statistically significant. This is due to the greater errors that appear in the case of 2D - TLC methodology. In the range of concentrations of plasma Phe higher than 360 μmol/L (which is the cut-off value for HPA), although in four cases there were statistically significant differences in the level of plasma Phe determined by the two methodologies, the value obtained by the 2D - TLC methodology was high enough to influence the decision of changing the diet so that HPA is kept under control. In addition, the intense spot of Phe on the 2D - TLC chromatogram may be detected even by un unexperienced laboratory specialist. Conclusion. The HPLC procedure for measurement of plasma Phe level is very suitable to be used in the routine management of PKU. The 2D - TLC procedure may be accompanied by relatively high errors; however, it detects patients with severe PKU.

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Bardet Biedl syndrome (BBS) is a rare autosomal recessive disease, characterized by clinical and genetic heterogeneity. Many genes are involved. BBS seems to be\r\ndifferent from Lawrence Moon BBS, although they share some clinical symptoms. The main clinical signs are obesity, pigmentary retinopathy, kidney malformations, and hypogenitalism. Our aim is to report a case with typical\r\nretinis pigmentosa, hypergonadotrophic hypogonadism and cerebellum cyst. Case report. A man aged 18 was referred for obesity and blindness. His family history was marked by obesity and diabetes mellitus type II. His medical history began very soon, as he was born with polydactyly, then he became obese and had difficulty to learn and to see. His blindness was progressive, and his puberty was delayed.\r\nClinical and biological exams showed: severe android obesity (BMI = 40kg/m?, waist circumference = 130cm), pigmentary\r\nretinopathy, small testes with high FSH = 17 mU/mL (1-8), and normal LH = 6.13 mU/mL (0.6-12)], empty sellae, cerebellum cyst, renal malformations, and signs of chronic infections. He did not have any spasticity or ataxia.\r\nGenetic study was not done. Conclusion. In this case, all features argued for typical BBS, except for testicular\r\ninsufficiency which is classically described as hypogonadotrophic. Infections should be treated vigorously to avoid renal insufficiency.

Obesity involves both genetic and environmentl influences, but the mechanisms of the genetic effects are not well understood.\r\nObjective. The aims of the study were to investigate the frequency of perilipin gene polymorphism in order to identify the relationship between insulin resistance and gene polymorphism in obese women.\r\nSubjects and methods. Study population included 31 obese women and 10 women with normal weight as a control group. All of the entire coding exons of PLIN gene were amplified by polymerase chain reaction (PCR). Insulin resistance (IR) was estimated using the homeostasis model assessment (HOMA-IR).\r\nResults. In the obese group, 29 (93.6%) patients were homozygous and 1 patients (3.2%) was heterozygous for the c.580C>.G (p.Pro194A1a)(rs. 6496589) mutation and 1 patient (3.2%) was Pro194A1a. Homozygous. Val156Leu. Heterozygous mutation at exon 5 at PLIN gene (p=0.072). As for exon 8 at PLIN gene in obese group, 6 patients (19.3%) had heterozygous for the c.1113T>C (Pro371Pro) (rs2304796) mutation, and 12 patients (38.7%) had heterozygous for the c.1113T>C and c.1119C>T (p. Val373Val) (rs2304795) mutation, and 4 patients (12.9%) had homozygous for the c.113T>C and c.1119C>T mutatons (p=0.009). In obese patients with no nucleotide substitution at exon 8, mean levels of systolic and diastolic blood pressures were higher than those of obese subjects with gene polymorphism. However, there were no statistically significant differences for HOMA-IR levels between obese women with and without perilipin gene polymorphism.\r\nConclusions: Perilipin gene polymorphisms such as heterozygous and homozygous for the c.1113T>C and c. 1119C>T (rs2304795) at exon 8 were associated with obesity risk. However, no relationship was found between insulin resistance and polymorphisms of perilipin gene in obese women.

In the latest decade, translational medicine has played an important role. In neuroendocrine tumor field, genetic results are associated with clinical and paraclinical disease implications. This translational knowledge allows a faster action in some mutation types with aggressive outcome. In the following pages we will make a review about actualities in translational approach from genetics to clinical neuroendocrinology.

Background. Fine needle aspiration biopsy (FNAB) is an important tool in the diagnosis of thyroid nodules. Aim. Our aim was to investigate the malignancy criteria in thyroid nodules by gray-scale ultrasonography (US) and duplex Doppler ultrasonography (DDUS), and their usefulness in reducing the number of unnecessary FNAB’s. Study design. This was a prospective observational study. Subjects and methods. 181 benign and 18 malignant thyroid nodules were evaluated by US and DDUS before FNAB or thyroidectomy. US was used to note size, shape, internal structure, nodule echogenicity, marginal properties, peripheral hypoechogenic halo, and microcalcifications. DDUS studies were used to evaluate the maximum and minimum flow velocity (Vmax and Vmin), systolic/diastolic flow velocity ratio (S/D), pulsatility index (PI), resistive index (RI), acceleration time (AT) and acceleration value. Results. Contour irregularity, size and presence of microcalcifications (p<0.001, p=0.02 and p=0.002, respectively) and S/D, Vmin, PI, RI and AT were significantly different (p=0.004, p=0.007, p=0.032, p=0.003 and p=0.003, respectively) were significant for malignant nodules. Benign and malignant nodules with or without suspicious US findings had similar DDUS findings. Vmax, Vmin, PI, RI, and AT were significantly different in the presence of microcalcification (p=0.043, p=0.001, p=0.031, p=0.04, and p=0.019 respectively). AT was significantly different in the case of absence of microcalcification (p=0.019). Comparing the irregular margins, Vmin, PI and RI were significantly different (p=0.014, p=0.003, and p=0.014 respectively). Conclusion. Benign and malignant thyroid nodules can be differentiated using gray-scale US findings and DDUS based indices together to reduce the number of unnecessary FNAB’s.

Introduction. Vinegar is known with its positive impact on post-prandial dysmetabolism. The aim of this study was to\r\nelucidate the acute effects of high amount vinegar on blood glucose and lipid parameters.\r\nMaterial and Methods. Sixteen type 2 diabetic patients who had been treated with metformin only, were served a\r\nstandardized meal to which 50 g vinegar was added on the first day but not on the second day. Blood glucose, insulin and lipid levels were measured during fasting and at the second hour after intake of the meal.\r\nResults. Postprandial increase in the levels of venous blood glucose measurements was not different in the vinegar group when compared with the reference group (p=0.163). There was no significant difference on postprandial insulinemia (p=0.796). While investigating the effect of the vinegar on postprandial lipemia, no differences in triglyceride\r\nchanges was found between vinegar and reference group (p=0.816).\r\nConclusion. In this study in which we have tried to find an answer to the question about the effect of high amount grape\r\nvinegar on postprandial metabolism, no favorable or deleterious effect on postprandial changes of glycemia and\r\nlipemia was found.

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Objective. The aim of this study was to compare the clinical effects of a triple oral antidiabetic combination versus basal insulin and metformin combination treatment in patients with poorly controlled type 2 diabetes.\r\nMethods. Eighty patients with type 2 diabetes, who were treated by metformin and sulphonylurea combination, and had\r\nHbA1c values between 7.5 and 10 % (58 and 86 mmol/L), were randomized into two groups. The first group was given triple oral antidiabetic therapy (pioglitazone, metformin, and sulphonylurea) and the second group was given metformin and a bedtime basal insulin (insulin detemir) combination for 12 weeks. Metabolic parameters were evaluated.\r\nResults. The mean fasting plasma glucose and HbA1c levels decreased in both groups. The decrease in HbA1c was slightly\r\nhigher in triple oral antidiabetic group (p=0.046). The patients in triple oral combination group gained 0.2 kg (p=0.881) and those in the metformin-insulin detemir combination group lost 1.7 kg (p=0.001) in 12 weeks (p=0.29 between groups). The frequency of hypoglycemia was higher in\r\ntriple oral antidiabetic group (11 vs. 2 episodes, respectively).\r\nConclusion. Both sulphonyureametformin-pioglitazone and insulin detemir-metformin therapies provided significant improvements in glycemic control. However, sulphonylurea,\r\npioglitazone and metformin combination led to more frequent hypoglycemic events, and weight management seemed in favor of insulin detemir-metformin combination.

Introduction. One of the diabetes complications in men is infertility. C-peptide and Nicotinamide have antidiabetic and antioxidant activity. So, the aim of this study was to investigate the effects of these drugs on male infertility caused by diabetes. Methods. In this experimental study 40 adult male NMRI mice (20- 25g) were obtained and randomly divided into 5groups: controls, diabetes model, diabetes+C-peptide, diabetes+Nicotinamide, diabetes+C-peptide+Nicotinamide. Diabetes induced was confirmed 3 days after administration of a single dose of streptozotocin (STZ) (65mg/kg) 15 min after an intraperitoneal injection of Nicotinamide (120mg/kg). Then C-peptide (25nmol/kg) and Nicotinamide (100mg/kg) were injected for 28 days. 24h after the last drugs injection serum samples, testes and cauda epididymis of animals were removed for hormonal, testis morphology and sperm count assessment. Results. Diabetes induced could decrease serum testosterone level and sperm count significantly (p<0.001, p<0.05 respectively). Serum LH, testosterone levels and sperm count increased in Diabetes+Cpeptide+ Nicotinamide versus diabetes group (p<0.05, p<0.001, p<0.01 respectively). Also administration of Nicotinamide alone showed an increase in serum testosterone (p<0.001). Conclusion. The results of this study demonstrated that combined administration of Nicotinamide and C-peptide improved diabetes induced male reproductive disorders by enhanced serum LH, testosterone levels and sperm count in diabetic mice.