ACTA ENDOCRINOLOGICA (BUC)

Context. Peripheral nerve lesions are a major complication of diabetes mellitus, the main clinical manifestations of which are numbness and pain involving the limbs. Objective. To determine the correlation between pregabalin treatment and diabetic peripheral neuropathic pain. Design. An experimental animal study in BALB/c mice. Subjects and Methods. Diabetes models are established by injecting streptozotocin (STZ) into the abdominal cavities of mice. The correlation between the treatment effect, time, and dosage of pregabalin was determined. The effect of a type 1 organic cation transporter (Octn1) in the absorption of pregabalin was evaluated. Results. Pregabalin reduced tactile allodynia in diabetic mice. The best analgesic effect occurred when intestinal absorption was increased. Octn1 mediated pregabalin entry into intestinal epithelial cells, which influenced the absorption of pregabalin with a timedependent fluctuation in the small intestine. Peripheral nerve damage caused by diabetes was dependent on time and dose of pregabalin, which was related to the regular expression of Octn1 in small intestinal epithelium. Conclusions. Peripheral nerve damage caused by diabetes was dependent on time and dosage of pregabalin, which was related to the regular expression of Octn1 in small intestinal epithelium.

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.

Objectives. Polycystic ovarian syndrome (PCOS) occurs in 6-10% of all women in their reproductive age. In women with PCOS, controlled ovarian hyperstimulation (COH) often results in an increased risk of ovarian hyperstimulation syndrome (OHSS). In vitro maturation (IVM) of human oocyte is an alternative technique for in vitro fertilization (IVF). The aim of this study was to compare the morphometric analysis and morphology of oocytes after invitro maturation (IVM) between normal women and those suffering from polycystic ovary syndrome (PCOS). Material and Methods. Thirty two women of 20 to 35 years of age that were undergoing controlled ovarian stimulation by the ICSI/IVF protocol were chosen for the study. The immature oocytes (n=108) were divided into two groups: the first oocyte group was comprised of 16 normal women (n=54); and the second group included 16 women with PCOS (n=54); then the oocytes were matured in vitro. After 24-48h of incubation, the oocyte maturation rate and morphometric and morphological characteristics were assessed using an inverted microscope, and then the images were compared. Results. There were significant differences in the maturity of oocytes between normal women and those with PCOS after IVM (P<0.05). Moreover, morphometric assessments revealed that there were no significant difference in the total diameter (μm) (zona thickness (ZPT) + perivitelline space width (PVS) + cytoplasm (CD) of oocytes between normal women and those with PCOS (156.3±6.8 and 137.7±9.9), respectively (P>0.05). Evaluation of morphological oocytes showed that morphological abnormalities, including ooplasmic vacuolization and granulation were higher in PCOS women compared to normal women (P<0.05). Conclusion. The increased quality of oocytes after IVM reflected a positive impact of IVM oocytes on normal women as compared to women with PCOS.

Background. Nephrogenic diabetes insipidus (NDI) is a disease characterized by a defective response to the antidiuretic hormone (ADH) of the renal collecting duct leading to a decline in the ability of the pro-urine concentration. Case presentation. A 23-year-old man presented with an over 20-year history of polyuria concomitant with hydronephrosis. The diagnosis of NDI was established by gene analysis as well as a water-deprivation and vasopressin test. All exons of arginine vasopressin V2 receptor (AVPR2) gene were amplified and sequenced. A novel hemizygous intragenic inframe deletion, cDNA 255th bp to 263th bp in exon 2 of AVPR2, was identified. These relevant translations from the 85th amino acid Asp to 88th amino acid Val were missed and replaced by amino acid Glu. After treating the patient with hydrochlorothiazide, his symptoms improved significantly. Conclusion. The genetic analysis revealed a novel X-linked intragenic inframe deletion, AVPR2 gene cDNA 255th bp to 263th bp, causing NDI.

Background: Published data sustain the participation of vascular renin angiotensin system (RAS) on alteration of pulmonary vessels reactivity during the allergic airway inflammation. Ghrelin is a growth hormone-releasing peptide involved in modulation of immune function.\r\nObjective: This study aims to investigate the interaction between ghrelin and local RAS from rat pulmonary vessels during ovalbumin ? induced allergic airway disease. Methods: The angiotensinogen (AGT) ? induced contractions were assessed on isolated pulmonary artery and veins from ovalbumin sensitized rats receiving either saline (OSR) or ghrelin (OSG) by endotracheal instillation. Experiments were performed in the absence or the presence of losartan, D-ALA7, chymostatin and N&#969;-nitro-L-arginine methyl ester (L-NAME).\r\nResults: The AGT contractile effects mediated by AT1 receptors were lower with at least 25% on vessels from OSG than from OSR. The D-ALA7 and L-NAME significantly increases the AGT ? induced contraction on OSG. The amount of nitric oxide released after stimulation with AGT is higher on OSG and it is blocked by D-ALA7.\r\nConclusion: Our results suggested that pulmonary delivery of ghrelin could modulate the local RAS from pulmonary vessels by promoted the angiotensin 1-7 mediated effects. These data sustained the existence of another possible way for ghrelin?s beneficial effects on the lung.

Objectives: to determine the 24-hours profile and the clinical implications of hyperchloremic metabolic acidosis (HCMA) following cardiac surgery with cardiopulmonary bypass (CPB).\r\nSubjects and methods: prospective and observational study set in cardiac anesthesia and intensive unit. One hundred patients with cardiac procedures with CPB, mean age 56 years, mean body weight 71 kg, were enrolled. Sampling of arterial blood for gas, acid-base parameters (pH, carbon dioxide partial pressure, base excess, concentration of bicarbonate and anion gap) and serum electrolytes (sodium, potassium, chloride) were performed at four time points: 30 min after induction of anesthesia (T1), after completion of CPB (T2), at 6 hours (T3) and at 24 hours postoperatively (T4). The volume of fluids administered intraoperatively and 24 hours postoperatively as well as major complications: bleeding, arrhythmias and organ dysfunctions (renal, pulmonary or neurological) were also registered. For statistical analysis we used a t-test (p<0.05).\r\nResults: Seventy-three (73 %) of the patients developed metabolic acidosis during the observation period. Sixty-six (66 %) patients had HCMA. Mean chloride concentrations were at T1, T2, T3, and T4: 103 mmol/L, 113 mmol/L, 111 mmol/L and 108 mmol/L, respectively. The chloride concentration was significantly higher at T2 and T3 as compared to baseline. There were no statistical differences between patients with and without HCMA, neither in the amount and type of fluids administered perioperatively, nor in the incidence of bleeding, arrhythmias, and organ dysfunctions.\r\nConclusions: HCMA is common after cardiac surgery. It is a transient and benign acid-base disturbance. In our low risk cardiac surgery patients, HCMA was not associated with major postoperative complications.

Introduction. Ectopic sphenoid sinus pituitary adenomas are a rare, benign pituitary tissue neoplasm, occurring separate from and without involvement of the anterior pituitary gland. We present a case of ectopic pituitary adenoma confined to the sphenoid sinus, asociated with an empty sella. Case report. A 52-year-old man was addmitted to our neurosurgical department with persistent headache and nasal obstruction of one year duration. Patient presented no endocrine abnormalities and no visual disturbances. MRI revealed a well-defined mass lesion in the sphenoid sinus, hypointense on T1-weighted images, hyperintense on T2-weighted images, with moderate heterogeneous gadoliniumenhancement. A primary empty sella was associated. Surgery was performed by transnasal transsphenoidal approach. The tumor was removed in a piecemeal fashion. The bony sellar floor was intraoperatively proven to be intact. The pathologic studies confirmed the diagnosis of ectopic nonfunctional pituitary adenoma of the sphenoid sinus. The postoperative course was uneventful. Conclusions. When encountering a tumor within the sphenoid sinus, an ectopic pituitary adenoma should be suspected. A clinical, imaging and endocrinologic evaluation must be undertaken, aiming to identify the nature of the lesion and to initiate the specific therapy. Surgery remains the only way of obtaining a definite diagnosis and cure.

Background. Adrenocortical oncocytoma (ACO) is exceedingly rare. To date, only 81 cases are reported in the English literature. Most of ACOs are nonfunctioning and benign.\r\nCase report. We describe a case of ACO incidentally diagnosed in a 54-yearold male patient. Physical examination, routine laboratory studies and hormonal tests were within normal ranges. Abdominal computed tomography (CT) and magnetic resonance imaging showed a large and\r\nheterogeneous tumor (9x7x6 cm) in the left adrenal gland with borderline malignant characteristics. Left adrenalectomy was performed for treatment purposes. The cut\r\nsurface of the resected tumor was heterogeneous with tan brown color with areas of extensive hemorrhage and necrosis.\r\nMicroscopically, the tumor consisted predominantly of large polygonal cells containing eosinophilic granular cytoplasm\r\narranged in a solid pattern with abundant hemorrhage and necrosis. The tumor showed a compressed remnant of adrenal\r\ncortex in the outer the capsule of the mass. No vascular and capsular invasion was noted, and mitotic figures were not\r\nconspicuous. Immunohistochemically, the tumor cells were diffusely and strongly positive for melan-A, vimentin, alphainhibin, weakly positive for synaptophysin and calretinin. The tumor was focal and erratively positive for pancytokeratin. No immunoreactivity was observed form\r\nchromogranin-A, CD10 or p53. The histological diagnosis was ACO with uncertain malignant potential.\r\nConclusions. ACO occurs rarely in adults and preoperative diagnosis is difficult, especially in asymptomatic cases.\r\nIt needs careful evaluation and surgical treatment. According to our knowledge, this is the 2th case of ACO in an adult patient from Turkey in English literature. We\r\ndiscuss this case and review the literature on this unusual entity.

Objective. To compare results of treatment of primary hyperparathyroidism (PHPT) in two teaching hospitals (eastern and western Europe) and to establish conclusions regarding quality of surgery for PHPT in Romania. Methods. We reviewed two prospectively collected databases of patients submitted to open minimally invasive parathyroidectomy (OMIP) for symptomatic PHPT in two centers from Romania and the United Kingdom (UK). We included patients with biochemically proven PHPT and positive pre-operative localization studies. We excluded patients with negative localization studies, suspected multiglandular disease, concomitant thyroid disorders and chronic renal failure. Results. 60 patients were included, 27 in group A (Romanian cohort) and 33 in group B (UK cohort). We noted significant differences between groups in pre-operative serum calcium and phosphorus levels (p<0.5). There were no differences between groups regarding the presence of symptoms; in group A we had significantly more patients with renal calculi history (p=0.02), digestive symptoms (p=0.006) and osteitis fibrosa cystica (p=0.01). Two patients from the UK group had lithium associated hyperparathyroidism and 2 patients had genetic disease. Intraoperative parathyroid hormone measurement (ioPTH) was available only for group B and frozen sections were selectively used in both groups. Both the adenoma size and weights were significantly higher in group A. The median operative time was significantly longer in Romanian group (p=0.001); in this group we noted the single conversion to traditional cervicotomy (3.7%) from all studied patients. In group A we noted two patients (7.4%) with failed parathyroidectomy and persistent PHPT; the cure rate was 92.5% for Romanian group and 97% for the UK group. Conclusions. OMIP can be performed safe with a high cure rate in “small” volume endocrine centres with results comparable to western experienced endocrine centres. Romanian patients presented with more severe PHPT with more frequent end-organ damage, due probably to late diagnosis.

Despite several attempts to establish the role of QUS in clinical practice, issues such as definition of osteoporosis based on QUS, screening strategy and therapy efficacy for patients identified by QUS as having high risk of fracture remain a matter of debate. The present study aimed to evaluate the diagnostic agreement between two QUS techniques (heel QUS and proximal phalanges QUS) and DXA in an unselected population of Romanian women aged 24- 80 years, as well as to offer cut-off levels for QUS to distinct between women with or without osteoporosis identified by DXA. In women measured by both DXA and calcaneus QUS (c- QUS), bone mineral density (BMD) moderately correlated with stiffness index (SI) (L1-L4: r=+0.51, p<0.001; femoral neck: r=+0.53, p<0.001; hip: r=+0.57, p<0.001), while in women examined by both DXA and phalanx QUS (ph-QUS), BMD was positively related to amplitude-dependent speed of sound (Ad-SoS) (L1-L4: r=+0.47, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001) and ultrasound bone profile index (UBPI) (L1-L4: r=+0.44, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001). At a T-score cutoff level of -2.5SD, the high specificity but low sensitivity suggests a low false positive rate of c-QUS as a diagnostic test; still, several patients with the disease may not be correctly diagnosed. At the same cut-off level, ph-QUS showed higher sensitivity and lower specificity. Diagnostic agreement between DXA and QUS was poor, with k-scores ranging from 0.33 to 0.39 for c-QUS and from 0.14 to 0.29 for ph-QUS, respectively. Lowering c-QUS T-score cutoff for lumbar spine osteoporosis screening to -1.5SD and ph-QUS T-score cut-off to -1.9SD, respectively, improved sensitivity and had a minor effect on diagnostic agreement. Regardless of the evaluated site, neither c-QUS nor ph-QUS does represent an adequate predictor of BMD in Romanian women. Changing the diagnostic T-score threshold from -2.5 SD to -1.5 SD and -1.9 SD in subjects examined by c-QUS or ph-QUS, respectively, is followed by improved sensitivity and diagnostic agreement in the identification of patients with vertebral osteoporosis. Cut-off values may allow QUS to be used as a screening tool for spine and femur osteoporosis.