ACTA ENDOCRINOLOGICA (BUC)

Context. Oral anti-diabetic drugs (OADs) are leading option for treatment of type 2 diabetes (T2D). However, availability of OADs are limited in the presence of renal impairment (RI). Objective. In this study, we examined the efficacy of repaglinide, which is mainly metabolized and excreted via non-renal route, in patients with T2D and severe RI that consists mainly of chronic kidney disease (CKD) stage 4. Design, Subjects and Methods. This was an open label, single arm, interventional study by repaglinide monotherapy. The primary efficacy end point was HbA1c change from baseline to week 12. Results. Repaglinide treatment significantly reduced HbA1c levels from 7.7 ± 0.7% to 6.1 ± 0.3% (p<0.001) in 9 patients with severe RI (mean estimated glomerular filtration rate was 26.4 ± 7.5 mL/min/1.73m2). Focusing on 4 patients who received DPP-4 inhibitor monotherapy at enrolment, switching to repaglinide also significantly improved HbA1c levels. No hypoglycemic symptoms or severe hypoglycemia was reported in patients who completed the period of 12 weeks. Conclusions. We demonstrated the efficacy of repaglinide in patients with T2D and severe RI. In case that DPP-4 inhibitors are not enough to achieve targeted range of glycemic control, repaglinide is another good candidate.

Context. Urolithiasis and obesity are now public health problems with an increased incidence worldwide. Management of urolithiasis in patients with morbid obesity is usually associated with higher morbidity and mortality compared to non-obese patients. ESWL is a nonsurgical procedure for the treatment of lithiasis. In obese patients the ESWL efficacy is influenced by the skin-to-stone distance or poorer detection of the calculus because of the fatty tissue. Objective. To highlight the overweight or obese lithiasic patient profile that could be best treated by ESWL. Subjects and Methods. We evaluated ESWL results in 1393 patients with kidney or ureteral stones between 5 and 20 mm. They were divided into 4 groups according to the BMI: Group A-overweight (BMI=25-30 kg/ m2); Group B-grade I obesity (BMI=30-35 kg/m2); Group C-grade II obesity (BMI=35-40 kg/m2) and a control group of normal weight (BMI=18-25 kg/m2). Results. Patients with a higher BMI required a greater number of ESWL sessions. A statistically significant greater number of patients with a waist circumference of >102 cm required more than 2 SWL sessions (p=0.007). Location of the stones in the pelvic ureter had the highest rate of success for obese patients (p=0.00001). The ESWL success rate in overweight and obese patients can be negatively influenced by BMI, abdominal circumference over 102 cm, and hardness of calculi reflected in the radiopacity on KUB. Conclusions. In patients with grade II obesity, pyelocaliceal calculus and increased hardness, other urological alternatives to lithiasis should be considered from the beginning.

Background. This study aimed to assess the mechanism through which Wnt/ beta - catenin signaling pathway, and StarD7, prometes testosterone synthesis, and to explore a new pathway for the regulation of testosterone synthesis. Animals and Methods. Leydig cells were isolated from male Sprague-Dawley rats divided into four groups and treated with Annexin 5 in concentration of 0, 0.1, 1 and 10 nmol/L. Testosterone secretion, expression of StarD7, StarD7 mRNA, β-catenin and changes of β – catenin localization in Leydig cells of testis of rats were tested in the four groups. Results. mRNA and protein levels of StarD7 and β-catenin increased significantly, upon stimulation with 1 nmol/L annexin 5. Accumulation of β-catenin inside the cells and the nucleus, was observed by immunofluorescence staining, in cells treated with annexin 5. These findings indicate a possible role of StarD7 and β-catenin in the process of annexin5-mediated stimulation of testosterone synthesis. Conclusions. Wnt/β-catenin signaling pathway and StarD7 are involved in the process of annexin5 stimulation of testosterone synthesis. Activation of Wnt/ β-catenin signaling pathway by Annexin5, and increase in StarD7 expression lead to elevated expression of key regulatory enzymes in testosterone synthesis, thus promoting testosterone synthesis.

Objective. Cardiovascular disorders in diabetes condition arise from increased oxidative stress. Both regular mild exercise and testosterone influence on body’s antioxidant system in diabetes. In this study, we evaluated treatment of testosterone and voluntary exercise, alone or together on oxidative stress in the heart and blood of diabetic rats. Methods. Type 1 diabetes was induced by intraperitoneal injection of 50 mg/kg of streptozotocin in rats. Sixty three rats have been divided into eight groups as follows: Diabetes, diabetes+ testosterone, diabetes+ exercise, diabetes+ testosterone+ exercise, diabetes+ castration, diabetes+ castration+ testosterone, Diabetes+ castration+ exercise, Diabetes+ castration+ exercise+ testosterone. Type 1 diabetes was induced by intraperitoneal injection of 50 mg/ kg of streptozotocin in the male Wistar rats and after a week, castration was performed. After 42 days of treatment with testosterone (2 mg/kg/day) or voluntary exercise alone or in combination, SOD, GPX and CAT activities and MDA levels were measured in the blood and heart tissue samples in the groups of study. In the end of study, SOD, GPX and CAT activities and MDA levels were measured in blood and heart tissue samples in the groups of study. Results. SOD, GPX and CAT activities significantly (p<0.05) increased in groups that treated either testosterone or exercise and MDA level significantly (p<0.01) decreased in the blood and heart tissue of diabetic and castrated diabetic rats. Simultaneously, treatment with testosterone and exercise had a synergistic effect on antioxidant enzymes level in diabetic and diabetic castrated rats. In the castrated animals with diabetes, SOD, GPX and CAT activities significantly decreased (p<0.05) and MDA levels significantly increased (p<0.05) in blood and heart tissue. Conclusion. Voluntary exercise and testosterone alone or together heightened body’s antioxidant system and were able to reduce the MDA levels in blood and heart of diabetic and castrated diabetic rats.

Context. Betel nut is consumed by millions of people for stress reduction and increased capacity to work. One of its components is arecoline which is useful for Alzheimer and schizophrenia; it also influences endocrine and gonadal functions. Objective. Objective is to examine whether arecoline can influence pineal-testicular function in metabolic stress. Design. Rats were deprived of food or water or treated them with arecoline, each separately for 5 days. Subjects. Pineal and testis with sex accessories were studied. Methods. Ultrastructural (pineal, testis, Leydig cells and prostate), hormonal (melatonin and testosterone) and other parameters (fructose and sialic acid) were examined. Pineal indoleamines were quantitated by fluorometric method; testosterone by ELISA, and carbohydrate fractions by spectrophotometric methods. Results. Inanition/ water deprivation caused pineal stimulation ultrastructurally (with enlarged synaptic ribbons) and elevation of melatonin level, but reproductive dysfunction by ultrastructural degeneration of Leydig cells and prostate with fall of testosterone, fructose and sialic acid concentrations. Arecoline treatment showed reversed changes to those of metabolic stress, but arecoline treatment in metabolic stress showed same results as in metabolic stress. Conclusion. The findings suggest that arecoline cannot alter the action of metabolic stress on pineal-testicular activity in rats.

Context. Management of neuroendocrine tumors is highly dynamic, in both diagnosis and treatment. Objective. Surgical resection with lymph node approach offers excellent 5-years survival. Design. Between 2008 and 2011 we operated with radical intent 326 lung cancers. Patients and Methods. Cases without lymph node approach were excluded. We found 38 neuroendocrine malignancies: 12 typical carcinoids, 3 atypical carcinoids, 4 large cell neuroendocrine carcinomas (LCNEC) and 10 small-cell lung cancers (SCLC). Limits of the study are: variable lymphadenectomy technique; absence of PET - CT and EBUS-TBNA (EndoBronchial UltraSound - TransBronchial Needle Aspiration) for staging; incomplete data for disease-free survival. Results. We performed 13 pneumonectomies, 22 lobectomies and 3 non-anatomical resections. There were 5 bronchoplasties. The 5-year survival difference between NSCLC (non-small-cell lung cancer - 42.9%) and SCLC (40.53% - one of the best from the literature) is not statistically significant (p=0.4780). Five-years survival was 100% for typical and atypical carcinoids – the best published. We found lymph node metastasis in 2 typical carcinoids, in 2 atypical carcinoids and in 6 SCLCs. Conclusions. For typical and atypical carcinoids, radical resection with lymphadenectomy offers 100% 5-years survival. Early-stage SCLC may benefit from radical resection; lymph node dissection is mandatory because of the well-known precocious lymphatic dissemination.

Context. With the widespread use of neck ultrasound, parathyroid incidentaloma (PI) emerges as an additional opportunity for incidental detection of primary hyperparathyroidism (PHPT). Objective and design. This study aimed to investigate PHPT cases detected by PI and to compare them with other PHPT patients. A retrospective analysis of newly diagnosed PHPT patients between 2014 and 2020 was conducted in our hospital. Subjects and methods. The cohort of 124 subjects was divided in two groups: 22 (17.7%) PHPT patients detected by PI (PI PHPT group) and the rest of 102 PHPT patients (non-PI PHPT group). Overall, 21 PIs were discovered on ultrasound and one was found during thyroid surgery. Clinical features, work-up and management of two study groups were compared. Results. The PI PHPT group had lower ionized calcium at diagnosis (p=0.034), lower peak serum calcium during follow-up (p<0.01), less fractures (p=0.022) and was less likely to meet the international criteria for parathyroidectomy (p<0.01). Positive sestamibi scan (p=0.022) and confirmed concordant localization in at least two different parathyroid imaging techniques (p=0.033) were more likely in the PI PHPT group. The frequency of surgical management did not differ between groups. Conclusions. PHPT detected by PI is clinically relevant and mostly comparable to PHPT in other patients with some features that correspond more often to a mild disease. Higher rate of positive preoperative localization in PHPT detected by PI might encourage parathyroidectomy even without the international criteria met.

Context. Cardiovascular risk is increased in women with polycystic ovary syndrome (PCOS). Do insulin sensitizing agents such as metformin (MET) and myoinositol (MI) ameliorate biomarkers of cardiovascular risk? Objective. To compare the effects of MET and MI on blood pressure, lipid profile and high sensitive C-reactive protein (hs-CRP) in women with PCOS in respect to their body mass index (BMI). Design. Open label, parallel randomized, single center study. Subjects and Methods. Sixty six women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of hormones, lipid profile, oxidized LDL (ox-LDL), hs-CRP, blood pressure measurement and clinical assessment of BMI, waist circumference (WC) and Ferriman Gallwey score (FG score) were performed before and after treatment. Results. Thirty patients in each group completed the trial. Compared with MET, MI significantly decreased diastolic blood pressure (DBP) (p=0.036) and significantly increased serum hs-CRP (p=0.043). No differences between groups in total cholesterol (TC), HDL-cholesterol, LDLcholesterol, ox-LDL and triglycerides were reported after 6 months. Treatment with MI reduced BMI (p=0.037), WC (p=0.005), DBP (p=0.021) and TC (p=0.008). During MET treatment a significant decrease in BMI (p=0.005), WC (p=0.004), FG score (p=0.001), testosterone (p=0.013) and free androgen index (FAI) (p=0.006) was observed. Conclusions. Our study showed an advantage of MI in reduction of DBP and TC thus predicting favorable metabolic and cardiovascular outcomes in PCOS women. MET more effectively decrease indices of hyperandrogenism.

Xanthogranulomas are inflammatory lesions exceptionally rarely occurring in the sellar region. Sellar xanthogranulomas (SXG) result from secondary hemorrhage, infarction, inflammation or necrosis upon existing craniopharyngioma (CP), Rathke`s cleft cyst (RCC) or pituitary adenoma (PA), or represent a stage in xanthomatous hypophysitis evolution. “Pure SXG” are independent of a preexisting lesion. A 70 year old male patient, laryngeal cancer survivor, presented with central diabetes insipidus (CDI). MRI revealed an intra-suprasellar mass of uncertain origin. Transsphenoidal surgery resulted in an efficient lesion resection with maximal pituitary sparing. Pathological report has confirmed SXG without conclusive identification of preexisting sellar lesion. Age at presentation and gender were atypical for SXG. The most frequent presenting signs of SXG were absent. Most SXG are initially misdiagnosed as CP, RCC or PA. Preoperative clinical and radiological uncertainty may impact operative planning. Differentiating from CP is crucial, due to divergent operative target goals and prognosis. Intraoperative frozen section analysis could guide surgical extensiveness. Close collaboration must include endocrinologist, neuroradiologist, neurosurgeon and pathologist. Quantity and quality of provided tissue are essential for avoiding bias in pathohistological analysis of cystic or heterogenous lesions. Awareness is needed of new pathological entities in the sellar-parasellar region. SXG should be considered in differential diagnosis of CDIcausing sellar lesions.

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.