ACTA ENDOCRINOLOGICA (BUC)

Context. Prognostic considerations include assessing the risk of liver fibrosis in people with nonalcoholic fatty liver disease (NAFLD). Objectives. This study evaluates the use of hematologic and metabolic parameters regarding liver steatosis and fibrosis scores (FLI and Fib-4) in non-obese type 2 diabetes mellitus (t2DM) patients with NAFLD. Methods. Subjects underwent abdominal ultrasound examinations, and FLI and Fib-4 scores were calculated to evaluate liver steatosis and the risk of liver fibrosis non-invasively: 61 non-obese NAFLD subjects with t2DM were included in the cohort study and were divided into 2 groups depending on the t2DM treatment regimen. Results. Fib-4 and WBC count demonstrated a significant inverse correlation (OR = 0.509, p = 0.007). WBC count had an R2 of 0.237, indicating that this marker could account for up to 23.7% of a variation in Fib-4. Fib- 4 and FFA had positive correlation which did not achieve statistically significant prediction (OR=7.122, p=0.062). Additionally, a significant prediction of HbA1c (OR=1.536, p=0.016) and haemoglobin (OR=1.071, p=0.020) for FLI was revealed. Conclusion. HbA1c and other haematological and metabolic parameters, such as haemoglobin and WBC, may be another non-invasive tool for determining whether nonobese NAFLD patients with t2DM are at risk of developing liver steatosis and fibrosis.

Context. Impaired flow mediated dilatation (FMD) and increased carotid intima media thickness (CIMT) are the antecedent forms of atherosclerosis. Objective. The aim of this study was to evaluate vascular structural and functional changes in patients with asymptomatic primary hyperparathyroidism (APHPT), and whether biochemical alterations, related with PHPT and oxidative stress marker serum advanced oxidation protein products (AOPPs), may have influence on vascular alterations. Design. This is a cross sectional clinical study. Subject and Methods: Thirty-four patients with APHPT and 29 sex- and age and cardiovascular risk factors matched control cases were included in this study. Endothelial function was evaluated by FMD of the brachial artery; CIMT was measured by ultrasonography; in addition serum AOPPs and biochemical parameters were determined. Results. Serum Ca levels were higher in the patient group [10.93±0.60mg/dL vs. 9.45±0.31; p<0.001]. FMD measurement was significantly lower in patients group [0.07 (0.01-0.26) % vs. 0.14 (0.04-0.22) %; p=0.01]. CIMT measurements were comparable between the groups [52 (35- 69) mm vs. 56 (38-70) mm; p=0.821]. AOPPs levels were significantly higher in the patients [136.43 (55.14-1352) mmol/L vs. 84 (53.18-595.48) mmol/L; p=0.026]. There were significant negative correlations between FMD and serum Ca (r=–0.339, p<0.001); and serum AOPPs levels (r=–0.275, p<0.005). Serum Ca (p=0.007, β=–0.353) and AOPPs (p=0.024, β=–0.243) levels and hyperlipidemia (p=0.024, β=–0.288) were the predictors of FMD. Conclusions. Vascular endothelial function is impaired in patients with APHPT. Hypercalcemia, increased oxidative stress and hyperlipidemia may have role in the pathogenesis of endothelial dysfunction in patients with APHPT.

Context. Atypical antipsychotics (AAs) are the first-line treatments for schizophrenia, schizoaffective disorder and bipolar disorder. However, they are now extensively utilized as off label in a myriad of diseases despite their frequently serious metabolic side-effects and hyperprolactinemia. Objective. The purpose of our study was to observe long-term (one year) prolactin level change in first episode schizophrenia patients treated with one of the four AAs: olanzapine, quetiapine, amisulpride, ziprasidone. Design. This study is an analysis of the prolactin level associated with the atypical antipsychotics used in European First Episode Schizophrenia Trial (EUFEST) study. Subjects and Methods. Seventy-three first episode schizophrenia patients from the 113 patients, randomized to one of the four AAs treatment arms. Prolactin level was obtained at baseline, 6 and 12 months for all the four AAs. Analyses have been done for each antipsychotic separately for each sex. Results. For the male patients neither of the four antipsychotics have been associated with a statistically significant increase of prolactin level in the entire study (p>0.05). In case of the female patients, treatment with olanzapine (p=.021) and ziprasidone (p=.005) has been associated with a decrease of prolactin level in one year compared with baseline. Conclusions. In both men and women, the administration of these four AAs is not associated with the increase of prolactin levels, moreover, in women’s case, there is a reduction of prolactin values at administration of Olanzapine and Ziprasidone. These results are optimistic, suggesting that long term administration of these antipsychotics is safe regarding prolactin level.

Background. Dehydroepiandrosterone sulphate (DHEA-S) is a major steroid product of adrenal glands and an important neurosteroid, but due to only slight androgenic activities pathology of DHEA-S secretion it was rarely described until now. Aim. To report a case of DHEA-S and testosterone secreting adrenal tumour with clinical manifestations of suddenly appeared epileptic seizures, amenorrhea, hirsutism, weight gain and decreased sexual activity before operation, and up to 12 months observation after surgical removal of the tumour. Methods. Presentation of clinical case with comments. Results. Epileptic seizures, amenorrhea, weight gain and hirsutism suddenly appeared in a 38-year-old fertile woman. A right adrenal tumour was detected. Blood levels of DHEA-S and testosterone were very high. Surgical removal of the adenoma (confirmed histologically) was performed what conditioned decrease of DHEA-S, testosterone and other hormones in 2-24 hours for the level of adrenal insufficiency. After a month all the hormones returned to normal level and were maintained at this level for 12 months after operation, excepting aldosterone, which increased gradually. Menses reappeared in six weeks after a short period of hot flashes and perspirations. Seizures did not appear in 12 months. Sexual activity was lowered one month before and after the operation, and it was maximal 6-12 months after operation. Conclusions. We report a case with complete recovery of a 38-year-old woman, presented with epileptic seizures, amenorrhea, hirsutism, weight gain and decrease of sexual activity, before and after surgical removal of DHEA-S and testosterone secreting adrenal tumour.

Context. Children having gonadal tumors and disorder of sex differentiation (DSD) are rare. Objective. To investigate the presentation of DSD children with malignant gonadal tumors. Methods. A retrospective study from 2010- 2020, that evaluated 17 children with DSD, including 13 females, eight months to 16 years, with congenital adrenal hyperplasia, 5-alpha reductase deficiency, androgen insensitivity syndrome, Turner, Sywer, and Klinefelter syndromes. Results. Ten children had malignant gonadal tumor; nine had germ cell tumors and one person granulosa cell tumors, while seven children with non-malignant tumor had gonadoblastoma, cystadenoma (five children), and cysts. Systemic malformations, obesity, elevated tumor markers, and psychosocial issues were observed in 90%, 90%, 70%, and 50% of children with malignancy unlike 28.6%, 42.9%, 14.35%, and 57.1% children without malignancy respectively. Most (9/10) children >12 years, had psychosocial issues, unlike 0/7 children ≤12 years. From 8/17 children presenting with symptoms suggestive of tumor, 75% had malignancy, while from 9/17 children with DSD presentation, 44% had malignant tumors. Malignancy was observed in 3/10 children between eight months to age six, while 7/10 children had stage 1-2 tumors. We reported a child, identified as female, aged 13 years, with partial androgen insensivity syndrome (PAIS) 46,XY, and testicular papillary serous cystadenoma with genomic variant AR NM_000044.4:c.2750del. p.(F917Sfs*27) chromosome Xq12, never published in people with PAIS nor population databases (GnomAD). Conclusion. DSD diagnosis raises numerous challenges. People with DSD have increased risk of malignancy, especially when obesity and, systemic malformations are present; also, psychosocial issues in these children are associated with postpubertal age.

Introduction. Vitamin D is involved in differentiation and induction of erythropoiesis in bone marrow cells. Aim. We compared the serum 25(OH) vitamin D level in obese children versus control and found correlations between vitamin D level and hematological indices in obese children. Materials and methods. 25 overweight and obese patients and 15 normal weight children were enrolled in an observational study . Results. In obese children, the serum level of 25(OH) vitamin D was significantly (p<0.04) lower (20.60 ng/mL) compared with the value from normal weight ones (25.63 ng/mL) and the body fat percentage BFP was higher. We found a positive correlation (r=0.44, p<0.05) between serum vitamin D and hemoglobin level and a negative one between serum vitamin D and the number of platelets (r= -0.43, p<0.05). Also, the serum iron was at the lower normal limit in the obese children and negatively correlated with the percent of the body fat (r= -0,62, p<0.05). Conclusion. Obese children have vitamin D deficiency. The hemoglobin level and the number of platelets are correlated with the serum level of 25(OH) vitamin D. Supplements with vitamin D may have pleiotropic effects, including those on bone marrow activity.

Objective. Hyperandrogenism is any clinical or laboratory evidence of androgen excess in women. This study was conducted to assess the prevalence of hyperandrogenic disorders especially polycystic ovary syndrome in a random sample of adolescent girls, as well as to identify the clinical, hormonal, ultrasonic, and body composition characteristics associated with such disorders. Patients and Methods. Two hundred school girls (15-18 years old) were selected by random sampling from different secondary schools, and screened for hyperandrogenic disorders by a validated questionnaire and subjected to thorough confirmatory investigations. Results. Twenty-five out of the 200 students were thoroughly evaluated. Eighteen adolescents of the examined students (72%) were finally diagnosed with polycystic ovary syndrome, 5 (20%) with idiopathic hyperandrogenism and 2 (8%) with non-classic congenital adrenal hyperplasia . Despite normal weight percentiles and body mass index for age and sex in 83.3% and 88.9% of students with polycystic ovary syndrome respectively, fat mass, trunk fat percentage, trunk fat mass, and trunk free fat were significantly higher in polycystic ovary syndrome patients compared to controls. Conclusions. Polycystic ovary syndrome was the most common hyperandrogenic disorder in this study. Combined menstrual dysfunction and clinical hyperandrogenism had adequate sensitivity and high specificity in the prediction of polycystic ovary syndrome. Pulse inversion harmonic imaging is an adequately sensitive preferential diagnostic tool of polycystic ovary syndrome in virgin adolescents who may have central adiposity. Body composition assessment by bioelectrical impedence is valuable in detecting central adiposity which could be correlated to parameters of insulin resistance.

Objective. To determine the long-term effect of weight loss on arterial stiffness, metabolic parameters in morbidly obese patients who underwent laparoscopic adjustable gastric banding (LAGB). Subjects. Forty-eight morbidly obese Caucasian subjects underwent LAGB from January 2009 to January 2010 and completed 4 years follow-up. Measurements. Patients were evaluated for body mass index (BMI), waist circumference, arterial blood pressure (BP), metabolic factors: leptin, adiponectin, glucose, glycated haemoglobin (HbA1c), insulin. Endothelial function - evaluated as reactive hyperemic index (RHI). Arterial stiffness - determined by cardio - ankle vascular index (CAVI). Results. Average BMI decreased from 46.48±7.06 kg/m2 to 39.78±7.36 kg/m2 (1year, p<0.001) and 37.29±7.49 kg/m2 (4years, p=0.012). The systolic BP and heart rate reduction were observed after the 4 years. Changes in cardiovascular parameters were accompanied by waist circumference reduction and improvement of glucose metabolism,reduction of insulin, HbA1c, leptin, C-reactive protein values. However, there were statistically significant increases in CAVI 6.58±1.77m/s vs. 7.03±2.00 m/s (p=0.014) at 1 year, but not significant 7.12±2.19 (p=0.153) after 4 years. Endothelial changes were observed only in diabetic patients one year after LAGB 2.18±0.57 vs. 1.86±0.34 (p=0.021) vs. 2.05±0.42 (p=0.086). Conclusion. Weight reduction induced by LAGB was associated with changes in body weight and metabolic parameters, but it was no improvement on endothelial function and arterial stiffness.

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Background. Thyroid nodules are a common pathology worldwide. Fine needle aspiration biopsy (FNAB) is an important diagnostic method for the investigation of malignancy in thyroid nodules. However, according to the Bethesda System used to classify the results, patients with atypia of undetermined significance/follicular lesion of undetermined significance (AUS / FLUS) may not be classified as benign or malignant. Therefore, it may be necessary to determine some clinical risk factors to apply the best treatment in these patients. Aim. To determine the factors that increase the risk of malignancy in this patient group. Methods. A retrospective study including 138 patients with an FNAB categorized as AUS/FLUS and operated between June 2015–September 2018. Demographical, Laboratory (TSH) and Ultrasound variables (number, size and characteristics of nodules) of the patients were compared among postoperative histopathological results. Results. Hypo-echoic structure, microcalcification and irregular margin of the nodules were detected to be associated with malignancy in patients with FNAB results of AUS/FLUS (p <0.001). Conclusion. We suggest that surgical treatment should be considered if the patients have nodules with the hypo-echoic structure, microcalcification and irregular margin with an FNAB histopathological result of AUS / FLUS.