ACTA ENDOCRINOLOGICA (BUC)

Diabetes is one of the most prevalent chronic disorders, associating numerous somatic and behavioral modifications. Oxytocin has been widely studied for its involvement in social behavior and psychiatric disorders. This pilot study presents a series of 3 patients with type 1 diabetes and diabetic neuropathy in which the values of plasma oxytocin, neurotensin, β-endorphins, α-MSH, substance P and orexin A were measured in comparison to 3 healthy controls with matching ages. In the diabetic patients group, there was a strong negative correlation between the value of plasma glucose and oxytocin (r=-0.99, p=0.04), respectively neurotensin (r=- 0.99, p=0.03). These values did not correlate in the control group. The results suggest that oxytocin, in conjunction with neurotensin, could be investigated as a potential early detection marker of diabetic neuropathy and, to our knowledge, this is the first report focusing on plasma oxytocin levels in patients with diabetic neuropathy.

Context. Open varicocelectomy is generally performed without microscopic equipment in Iran. We report our experience with loupe-assisted inguinal varicocelectomy, and its impact on semen parameters and pregnancy rate. Subjects and Methods. We conducted a retrospective interventional study on secondary data obtained from the medical records of 303 men with varicoceles, who underwent an inguinal varicocelectomy between March 2003 and April 2012. The surgical technique involved the use of a 3.0 × loupe during spermatic cord dissection at the level of the internal inguinal ring under spinal anesthesia. Semen samples were analyzed for sperm concentration, motility, and sperm morphology before the varicocelectomy and after 3 months. All the infertile patients were followedup postoperatively for more than 1 year. Results. There were 9 (3.0%) varicocele recurrences and 3 (1.0%) hydroceles. After varicocelectomy, sperm concentration and motile spermatozoa increased. In addition, spermatozoa with normal morphology improved significantly postoperatively. Of the 303 subjects treated, 153 (83.2) had a 1-year preoperative history of infertility; the spontaneous pregnancy rate of the spouses during the follow-up period was reported to be 61.4%. Conclusions. The results of this research indicated that varicocelectomy using loupe-assisted inguinal technique could improve semen parameters and pregnancy rate with a low postoperative complication rate.

hormone (ACTH) mediated multisystemic state of adrenal hypercortisolism. An ACTH secreting benign pituitary tumor (adenoma) is the most common cause in the majority of patients with CD. Case report. This article describes a case of a 56-year-old woman presenting with clinical manifestations of hypercortisolism, with high plasma cortisol and ACTH levels that was suppressed with high-dose dexamethasone administration, suggestive of CD. Pituitary magnetic resonance imaging (MRI) of the sellar region was inconclusive. During the single photon emission computed tomography (SPECT) examination, an increased accumulation of technetium - 99m - hexakis - 2 - methoxy - isobutyl-isonitrile (99mTc-MIBI) in the pituitary gland area was noticed. Finally, response to corticotropinreleasing hormone (CRH) and ghrelin stimulatory testing, differentiated CD from ectopic ACTH and primary adrenocortical hypersecretion. Conclusion. We highlight the potential of 99mTc- MIBI SPECT as sensitive and specific method of pituitary gland adenoma detection in patients with Cushing’s disease, when MRI fails to directly detect an adenoma and stimulatory tests with CRH and ghrelin are not in routine diagnostics.

Context. Noninvasive encapsulated anaplastic thyroid carcinomas (NE-ATCs) have been described in few case reports, and consistently associated with favorable outcome compared to the classical ATCs. Objective. Our aim is to remark a rare histological finding in ATCs, encapsulation, which has been associated with a favorable outcome. Design. We have documented a rare case of an NE-ATC with its clinical, pathological, and molecular features. We also provided a thorough discussion of all the encapsulated ATCs reported in the literature. Subjects and Methods. A 50-year-old woman with an unremarkable medical history, who presented with a thyroid nodule, and diagnosed as “follicular lesion of undetermined significance” by fine needle aspiration biopsy. The patient was lost to follow-up for six years and revisited upon her neck disturbances and underwent total thyroidectomy. Results. Sections of the right lobe revealed a grossly encapsulated nodular lesion, measuring 75x55x55 mm. Histologically, the tumor consisted of both carcinomatous and sarcomatous components supported by immunohistochemical stains. Necrosis and atypical mitotic figures were evident. Capsular and/or vascular invasion was not identified. There were no BRAF codon 600, KRAS, NRAS mutations and RET/PTC rearrangement. During three-month follow-up, the patient was free of disease without adjuvant therapy. Conclusion. Encapsulated ATCs tend to follow a favorable clinical course and may deserve conservative treatment approaches.

Background and Purpose. Fibroblast growth factor 21 (FGF21) has recently been identified as a metabolic regulator, but its physiological role is still not completely known. The aim of this study was to evaluate serum FGF21 levels in an Iranian population with type 2 diabetes. Materials and Methods. This cross-sectional study was conducted in patients with type 2 diabetes. All patients were evaluated for fasting serum levels of glucose, glycated hemoglobin (HbA1c), lipids, urea and creatinine. Participants were divided into two groups with poorly-controlled and wellcontrolled diabetes based on their HbA1c levels. Healthy nondiabetic subjects (matched with patients in terms of age, sex and body mass index [BMI]) were also recruited as control group. Serum FGF21 concentrations were determined in all subjects using ELISA. Results. Of the evaluated 141 subjects, 49 (34.8%) were categorized as having well-controlled diabetes, 66 (46.8%) had poorly-controlled diabetes, and there were 26 subjects in the normal control group. Mean serum FGF-21 concentration was 337.89±283.67 ng/L in the diabetic group and 237.25±43.22 ng/mL in the non-diabetic group (p<0.001). Mean serum FGF21 level was 237.25 ± 43.22 ng/mL in the control group, 309.81 ± 301.68 ng/mL in the well-controlled diabetic group, and 358.73 ± 269.98 ng/mL in the poorly controlled diabetic group. Serum FGF21 level in the poorly controlled diabetic group was significantly higher than that in the well-controlled diabetic and the healthy control groups (p=0.02) but there was no significant difference between the well-controlled and healthy groups. There was no significant association between serum FGF21 levels with lipid levels, presence of diabetic complications and BMI (p > 0.05). Conclusions. The present results suggested an association between elevated serum levels of FGF21 and poor control of diabetes. Future studies are warranted to elucidate the prognostic role of these elevated levels of FGF21 in diabetic subjects.

Context. Vitamin D, a fat-soluble prohormone, is synthesized in response to sunlight and plays several roles in the body. Objectives. To determine Vitamin D status among healthy, young female medical students studying at King Saud University, Riyadh, Saudi Arabia, and to study the effects of nutritional and environmental factors on Vitamin D level. Study design. It is a prospective, observational, cross-sectional study conducted between December 2012 and March 2013. Subjects and methods. One hundred and seventy eight healthy medical students participated in the study. Each subject completed a questionnaire about vitamin D deficiency and attitude towards related environmental and nutritional factors, including duration of sunlight exposure, and vitamin D supplements. Serum levels of 25-hydroxyvitamin D, parathyroid hormone, calcium, phosphorus, and alkaline phosphatase were obtained.Results. The mean serum vitamin D level of the study group was 41.41±29.31 mmol/L (normal 75–250 mmol/L). Out of 178 participants, 126 (70.8%) were vitamin D deficient (<50 mmol/L), 29 (16.3%) had insufficient vitamin D (50–75 mmol/L), and 23 (12.9%) had normal vitamin D level (>75 mmol/L), with mean serum levels of 25.52±10.89, 62.84±7.04 and 101.41±9.1 mmol/L, respectively. In comparison between vitamin D deficient and nondeficient groups, daily milk consumption (P < 0.001), use of vitamin D supplements (P < 0.0001), and frequency of sun exposure for ≥ 5 days/week (P < 0.006) were significantly higher in the nondeficient group. Conclusion. Prevalence of vitamin D deficiency among female medical students in Riyadh is high and may be attributed to nutritional, social and environmental factors.

Background. Type 1 diabetes mellitus is a common disorder which causes a variety of complications such as cognitive deficits in central nervous system. Auditory P300 event related potential is a wellestablished neurophysiologic approach in the assessment of cognitive performance. In this study, we aimed to evaluate the cognitive performance in insulin dependent diabetic patients by auditory event related potentials. Methods. In this descriptive analytical and non-interventional study, auditory P300 event related potential was measured in oddball paradigm by using two tone burst stimuli (1000 & 2000 Hz) on 25 diabetic patients and 25 age, education and sex matched healthy controls, with mean age 28.76±4.1 in patients and 29.68±3.6 in controls. Results. The mean P300 latency of the diabetic patients was significantly prolonged and the mean P300 amplitude of the diabetic patients was significantly lower when compared with that of controls at all electrode sites (p<0.01). Also there was a strong correlation between P300 latency and glucose level, HbA1c and diabetes duration (p<0.01). Conclusion. Auditory information processing is slower and the speed of information categorizing is lower in diabetic patients than in controls.

The nuclear receptor coding PPARγ2 (PEROXISOME PROLIFERATORACTIVATED RECEPTOR-GAMMA; *601487) gene influences the lipid and carbohydrate metabolism via multiple pathways and is a candidate for the metabolic syndrome. In this paper we studied the relationship of the CCG (Pro) → GCG (Ala) polymorphism of the gene with the metabolic syndrome diagnosed according to the criteria recommended by the International Diabetes Federation (IDF) in 2005, in a population from central Romania. We have carried out a case-control study on 144 patients and 73 control subjects. Routine biochemical assays have been carried out, fasting insulinemia was measured by ELISA, and insulin sensitivity was assessed by calculating the HOMA and QUICKI indices. Genetic analysis was done by PCR followed by digestion with the restriction enzyme BstU I. The results show that the Pro12 allele had a higher frequency in the group of patients as compared to the healthy controls (76 vs. 65.7%, p<0.05). The risk for developing the metabolic syndrome in the presence of the Pro12 allele in a homozygous combination was found to be low but statistically significant (PP vs. PA + AA: OR = 1.98, CI 95% 1.04 -3.78, p = 0.046). In conclusion, in the local population, the Pro12 allele of the PPARG2 gene seems to contribute to the hereditary predisposition of the metabolic syndrome diagnosed according to the recommendations of the IDF, most likely as part of a polygenic system. Probably the absence of the protective Ala12 allele increases the risk for developing the disease.

Context. Vitamin D is a steroid hormone that acts by binding to the vitamin D receptor (VDR) found in many tissues. According to the long-term mechanism, vitamin D causes the proliferation and differentiation of muscle cells by gene transcription. Objective. We aimed to evaluate the relationship between muscle strength and serum vitamin D levels in elderly men. Design. Cross-sectional study. Subjects and Methods. Male patients over age 50 were included in the study. Study population was divided into 2 groups with handgrip strength according to body mass index, either as subjects with weak or with normal handgrip strength test (HGST). Vitamin D levels and other variables compared between weak and normal groups. Results. Vitamin D level of weak and normal groups were 7.5 (3-19.9) μg/L, and 11.6 (11.6-34.9) μg/L, which means significant reduced vitamin D levels in weakness group (p=0.01). Vitamin D levels were significantly correlated with HGST levels (r:0.362, p=0.001). Vitamin D levels were found to be an independent predictor of weakness according to HGST in logistic regression analysis (OR: 0.453, 95% Cl:0.138-0.769, p=0.05). Conclusions. Low vitamin D level is an independent risk factor for muscle weakness in men aged more than 50 years. Therefore, vitamin D levels should be screened and early replacement should be initiated for the sake of improvement of muscle strength in elderly subjects that vulnerable for frailty.

Background. The high recurrence rate and low survival rate of ovarian cancer (OC) patients are closely related to an anoxic environment. We aim to study the mechanism of long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) on hypoxia ovarian cancer cells (OCC) and its mechanism was investigated. Methods. Knockdown and overexpression of HOTTIP in human OCC (SKOV-3, OVCAR3) were performed. The expression levels of HOTTIP and HIF- 1α were monitored by qRT-PCR and WB. Transwell was conducted to validate the cell migration and invasion. ELISA was performed to calculate VEGF concentration in cells. Cell viability was monitored by CCK-8. Cell apoptosis and cycle were tested by flow cytometry. RNA pull-down was used to analyze the interaction between HIF-1α and HOTTIP. Results. HOTTIP was highly expressed in OCC. After HOTTIP knockdown, HIF-1α expression and VEGF concentration in OCC were decreased. Cell migration, invasion, and cell viability were decreased. Cell apoptosis rate and G0/G1 phase cells were increased. RNA pull-down indicated a direct interaction between HIF-1α and HOTTIP. Conclusions. HOTTIP formed a positive feedback loop with HIF-1α to promote the development and metastasis of hypoxia ovarian cancer. This study provided theoretical support for the development of new OC treatment strategies.