ACTA ENDOCRINOLOGICA (BUC)

Aim. The aim of this study is to present the personal experience of the authors regarding the use of positron emission tomography-computer tomography fusion image (PET/CT), with 18Ffluoro-2-deoxy-D-glucose (FDG), in the follow-up of differentiated thyroid carcinoma (DTC).\r\nPatients and Methods. Twenty seven cases of DTC admitted and treated in the “Prof. Ion Chiricu??” Institute of Oncology Cluj-Napoca (IOCN), performed PET/CT investigation\r\nbetween 2007 and 2009, in DOTE Centre Debrecen (Hungary) and Pozitron Center Oradea (Romania). The patients underwent the surgical intervention and had histology of differentiated carcinoma; they received radioiodine therapy with I-131, had suppression therapy with thyroid hormones and had in the follow-up whole body scans (WBS) with I-131, neck ultrasound and serological determination of thyroglobulin (Tg) and anti-thyroglobulin antibodies (anti-Tg). All patients were referred to PET/CT after radical treatment, after a negative WBS I-131 and a dynamic increase of the serological level of Tg or anti-Tg, without any clinical signs of\r\nrecurrence and no neck ultrasound pathological findings.\r\nResults. All patients included in this study presented abnormal levels of Tg: between 2.76 ng/ml and 4173 ng/ml, with a median value of 43.15 ng/ml. In 23 cases (85.1%) the PET/CT results revealed the neoplasm recurrence, in 3 cases we obtained true negative results and in 1 case a false negative image; in 2 cases (7.4%) we found a second malignancy. All patients needed to change the treatment strategies.\r\nConclusion. The significant increase of the number of DTC and the more aggressive behaviour of the disease in some situations, determines the existence of a clear strategy of\r\ntreatment and monitoring, where the role of PET/CT is well defined.

The determination of cardiac peptides at rest and during exercise stress testing (ET) represents a useful tool for the diagnosis of heart failure patients, but their usefulness in isolated LV diastolic dysfunction was less studied until now.\r\nAim. The aim of this study is to compare the effect of ET upon cardiac peptides in patients with left ventricular systolic and diastolic dysfunction.\r\nMethods. There were studied 101 heart failure patients, 58 with systolic LV dysfunction (LVEF 37.8%) and 43 patients with isolated LV diastolic dysfunction, mainly with hypertension (31 cases). All patients were submitted to a symptom-limited ET on cycloergometer, blood samples being obtained before ET and at peak effort. The plasmatic levels of N terminal pro brain-type natriuretic peptide (NT-proBNP) were determined using ELISA method (n.v. <250 fmol/ml). The systolic and diastolic LV functions were determined by echo-Doppler, according to ESC guidelines.\r\nResults. The results showed that the rest NT-proBNP values were increased in patients with LV systolic dysfunction (640?220 fmol/ml) in comparison with diastolic dysfunction (419 ?120 fmol/ml), p<0.01. At peak effort NT-proBNP increased to 790?242 fmol/ml (23%) in patients with systolic dysfunction (p<0.04) and to 490.2?179 fmol/ml (17%) in patients with diastolic dysfunction (p= NS). There was a close relationship between rest and exercise NT-proBNP values in both systolic (r=0.99, p< 0.05) and diastolic (r=0.72) LV dysfunction. \r\nIn conclusion, in heart failure patients with both systolic and diastolic LV dysfunction, NT-proBNP is increased at rest and during exercise, the increase being significant for patients with LV systolic dysfunction, probably in relationship with more important hemodynamic abnormalities.

Central precocius puberty (CPP) is characterized by abnormalities in the setting up of the gonadotropin ?pubertal? release, which occurs earlier. The gonadotropin releasing hormone (GnRH) was used initially to test the pituitary regarding FSH and LH release in both precocious and delayed puberty. Various GnRH superagonists were used for the same purpose, including triptorelin. A triptorelin test was applied to 14 girls with premature thelarche by using the subcutaneous administration of 0.1 mg/sqm and blood sampling at 2, 3 and 4 hours for serum LH and FSH and at 24 hours for serum estradiol. Serum mean levels of LH were >7.8 mIU/ml at all intervals, suggesting a ?pubertal? type of LH release. As concerns the individual levels of LH, only 5 out of 14 girls showed a value greater than 8 mIU/ml, which is the cutoff limit for the diagnosis of precocious puberty. These girls also met the other clinical and radiological criteria necessary for the diagnosis of precocious puberty. It was concluded that soluble triptorelin may be useful in detecting ?pubertal? type of LH release in girls exhibiting premature thelarche. Regarding the FSH and estradiol levels, they were considered irrelevant for the diagnosis.

Introduction. Vitamin D deficiency has been proven to have a deleterious effect on bone remodeling and bone mineral density, by inducing secondary hyperparathyroidism. The lack of a present consensus on optimal serum 25(OH)D levels required for the preservation of physiologic bone metabolism renders its follow-up difficult.\r\nMaterials and Methods. The cross-sectional study was performed on a sample of 69 healthy men aged 50-70. Serum 25(OH)D, total testosterone, sex hormone binding globulin, s-CTX (Crosslaps), and osteocalcin were assessed. BMD was measured by DXA at lumbar spine and hip levels. Statistical relationships between these parameters were calculated.\r\nResults. We found a significantly negative correlation between 25(OH)D and s-CTX (r = -0.30. p<0.05), but not between 25(OH)D and osteocalcin, although s-CTX correlated positively with osteocalcin (r = 0.49, p<0.001). Serum CTX was negatively correlated with lumbar BMD (r = -0.35, p<0.001), while osteocalcin was negatively correlated with total hip BMD (r = -0.26, p<0.01). Comparing mean s-CTX levels in insufficient and sufficient subjects at different cut-off points for 25(OH)D, significant differences appeared the strongest at 60 ng/ml. The percentage of 25(OH)D deficient or insufficient subjects was 50.7% at a 30 ng/ml cut-off point.\r\nConclusions. The results of the present study confirm the benefit in maintaining a normal bone turnover offered by serum 25(OH)D in the upper normal range. The large percentage of patients with vitamin D insufficiency reinforce the necessity of a specific follow-up and of epidemiologic studies dedicated to our geographic area.

Context. Persistent inflammation and impaired neovascularization are important contributors to the development of diabetic retinopathy (DR). Gene polymorphisms of adiponectin (APN) were demonstrated to have an important role on the plasma level and activity of adiponectin. APN has anti-inflammatory, anti-diabetic and anti-atherogenic properties. Toll-Like Receptor 4 (TLR4) is a critical mediator of innate immunity. Polymorphisms in TLR-4 gene were shown to be associated with impaired inflammatory response in diabetes. Objective. The aim of the study was to analyze the association of +276G>T variant of APN gene and Asp299Gly and Thr399Ile of TLR-4 gene variants in relationship with T2DM and DR in an Eastern European population group. Design. The distribution of the mutant alleles in 198 T2DM patients with DR and 200 non-T2DM controls was examined. Genomic DNA from T2DM patients and healthy controls genotyped through the use of PCR-RFPL assay. Results. Genotype and allele frequencies of the Asp299Gly and Thr399Ile polymorphisms differed between T2DM patients and non diabetic subjects (P<0.001). Moreover, the presence of the minor alleles of these polymorphisms were significantly identified as protective factors against T2DM, under a dominant model of Fisher’s exact test (χ2=4.988, phi=0.745, OR=0.767, 95% CI=0.602-0.867, P<0.001; respectively χ2=5.254, phi=0.820, OR=0.487, 95% CI=0.211- 0.648, P<0.001). Genotype analysis for the adiponectin 276G>T gene polymorphism yielded no significant association with T2DM, but revealed a borderline significance for the association with DR (χ2=5.632, phi=0.423, OR =1.101, 95% CI=0.887-1.203, P=0.009). Conclusions. We found an association between the TLR4 Asp299Gly and Thr399Ile polymorphisms and protection for DR. The APN genetic polymorphism is not associated with T2DM.

Vitamin D deficiency and insufficiency are common medical problems worldwide as they\r\nare quite prevalent in both healthy adults and individuals with osteoporosis, hospitalized patients\r\nand free-living and institutionalized elderly. The lack of serum 25-hydroxy-vitamin D (25OHD)\r\nassays standardization, variability of reference population, and the use of different cut-off points\r\nhave produced quite different prevalence reports from epidemiological studies.\r\nWe investigated the vitamin D status (deficiency, insufficiency, sufficiency) in 1048\r\nRomanian postmenopausal women with osteoporosis referred to our clinic for diagnosis and\r\ntreatment in the last three years. Most patients were untreated with osteoporosis drugs and nonsupplemented\r\nwith vitamin D. In our country dietary sources of vitamin D are scarce and there\r\nis no fortification of food with vitamin D. We found a high prevalence of both vitamin D\r\ndeficiency (25OHD < 10 ng/mL) - 22.23% and insufficiency (25OHD=10-30 ng/mL) - 61.26%.\r\nOur study also revealed a high prevalence of low vitamin D when using other cut-offs as reported\r\nin the literature. 83.49% had values lower than 30 ng/mL and 60.97% lower than 20 ng/mL. In\r\nthis study we identified a serum 25OHD concentration of 35 ng/mL above which serum\r\nparathyroid hormone (PTH) concentration attains a plateau at about 35 pg/mL. The relation\r\nbetween serum PTH and 25OHD concentration was non-linear and a log-log diagram showed a\r\nvery weak correlation. The prevalence of secondary hyperparathyroidism was 32.25% in the\r\nwhole population studied. It ranged from 40% in the subgroup of serum 25OHD less than 10\r\nng/mL to less than 15% in patients with 25OHD higher than 30 ng/mL.\r\nIn conclusion, in a representative osteoporosis population from Romania we found a very\r\nhigh prevalence of vitamin D deficiency and insufficiency whatever the cut-off used for\r\ndefinition.

Though increased BMI represents a risk factor for developing heart failure, in heart failure (HF) patients it paradoxically increases survival. This effect was not\r\nstudied in relationship with BNP and ACE mutations. Objective. To investigate the relationship between BNP fragment (8-29) plasmatic level, ACE I/D polymorphism and BMI in patients with chronic congestive heart failure. Methods. We studied 50 patients with HF, NYHA III and IV, mean age 64.96?13.24 years, 21 patients with BMI &#8805;30 kg/m2 vs 29 patients with BMI<30 kg/m2. BMI, ACE polymorphism,\r\nthe plasmatic levels of BNP fragment (8-29) were determined.\r\nResults. Mean plasmatic BNP fragment (8-29) level was\r\n1891.02?1008.06 pg/mL, mean BMI value 29.09?7.59 kg/m?, with a negative correlation between the two parameters (r=-\r\n0.46), stronger in women (r=-0.79 vs. r=-0.32 in men). Significant greater value of BNP fragment (8-29) was registered in nonobese patients (2130.77?866.58 pg/mL vs. 1547.765?1135.744pg/mL, p<0.05). The distribution of ACE mutation was: DD allele 36%, II allele 24%, and ID allele 40%. In all three groups, the patients with BMI &#8805;\r\n30kg/m2 presented lower values of BNP fragment (8-29) levels.\r\nConclusion. In HF patients, there was an inverse correlation between BNP value and BMI, obese patients having lower BNP fragment (8-29) values, no matter the ACE\r\npolymorphism.

Background. The pathogenesis of pre-eclampsia involves inflammation, endothelial\r\ndysfunction and enhanced oxidative stress. Interleukin (IL)-6 is a major pro-inflammatory\r\ncytokine, while leptin is released in large amounts by the adipose tissue, but also by placenta.\r\nAim. The present study aims to evaluate total maternal serum leptin and IL-6 levels in\r\npre-eclampsia compared to normal pregnancy and non-pregnant status.\r\nMethods. We enrolled 65 women in a transversal study; pre-eclampsia was diagnosed\r\nin 25 (group 1), 25 women had a normal pregnancy (group 2), while in 15 pregnancy was\r\nexcluded. Groups were matched for chronological and gestational age and body mass index\r\n(BMI) accordingly. Total serum leptin and serum IL-6 were determined using ELISA, after\r\nan overnight fasting period of at least 12 hours.\r\nResults. Both leptin and IL-6 concentrations were significantly higher in women in the\r\nthird trimester of pregnancy developing pre-eclampsia compared to normotensive pregnant\r\nwomen (p=0.001). Normal pregnancy was characterized by increased serum leptin levels\r\n(p=0.001) as well as increased IL-6 levels (p=0.001) in comparison to non-pregnant status.\r\nIn women with pre-eclampsia, leptin was positively and significantly correlated with\r\ndiastolic blood pressure (r=0.45, p=0.02), proteinuria (r=0.48, p=0.01) and uric acid values\r\n(r=0.39, p=0.04) and inversely related to HDL cholesterol levels (r=-0.64, p=0.0001).\r\nLikewise, IL-6 was positively related to systolic and diastolic blood pressure (r=0.41,\r\np=0.008 and r=0.60, p=0.00003, respectively), proteinuria (r=0.38, p=0.01) and uric acid\r\nvalues (r=0.43, p=0.004). However, leptin had no correlation with pregnancy outcome in\r\nwomen with or without pre-eclampsia. In contrast, IL-6 was negatively correlated with both\r\nfetal birth at weight (r=-0.35, p=0.02) and Apgar score (r=-0.38, p=0.01).\r\nConclusions. In conclusion pre-eclampsia associates significantly increased serum\r\nleptin concentrations and IL-6 production compared to normal pregnancy. In contrast to\r\nleptin, IL-6 may predict pregnancy outcome (fetal birth weight and Apgar score) in women\r\nwith pre-eclampsia.

Context. Estimation of osteoporotic hip fracture incidence and Romanian FRAX model were based on nationally reported hospital ICD 10 coding admissions of all hip fractures (without a validation process). Objective. We aimed to calculate, based on individual hospital charts analysis, the incidence of osteoporotic hip fracture in the main urban area of Romania and compare it with data reported to the National Institute of Public Health (NIPH). Design. We retrospectively analyzed the charts of all patients (>40 years old) admitted for hip fracture in a 12-month period in hospitals with an Orthopedic Department in Bucharest and surrounding Ilfov County (11.8% of Romania population). Subjects and Methods. All ICD 10 fracture and event/fall codes were validated against the charts. We calculated the age and sex adjusted incidence of osteoporotic hip fracture and used the national reported hip fracture data base for comparison. Results. There were 2203 hip fractures of which 1997 (90.65%) were fragility fractures. The crude incidence of low-energy hip fractures was 171/100,000 (225/100,000 in women, 103/100,000 in men). The incidence rose with age to a maximum rate of 1902/100,000 in women >85 years. The NIPH-reported incidence of hip fracture was 181/100,000 for the region of interest and 176/100,000 at the national level. Conclusion. The incidence of osteoporotic hip fracture was lower than the incidence based on hip fractures reported codes in the national database, but the incidence of fragility fractures calculated by our group was higher than the incidence reported in previous national studies. Nationwide studies are warranted.

Endocrine disruptors (EDs) are considered to have an impact on the function of reproductive axis at different levels as well on reproductive organs in both sexes. Complexity of female reproductive system influenced with various stressors including EDs lead to morphological and functional alterations. This is resulting in modulation of neuroendocrine regulation with consequent developmental irregularities and derangements, causative infertility, endometriosis as well as premature ovarian insufficiency or polycystic ovary syndrome. A number of experimental clues was obtained on female animal models using various EDs such as synthetic estrogens and phytoestrogens, neurotransmitters, pesticides or various chemicals. These substances lead towards consequent derangement of the neuroendocrine control of reproduction from early phases of reproductive development towards different phases of adult reproductive period. This text will address some novel insights into the effects of EDs on neuroendocrine regulation of gonadal axis, effects on ovaries as well on endometrium during implantation period.