ACTA ENDOCRINOLOGICA (BUC)

Detecting the primary tumours in carcinoid malignancies is a critical challenge. We report the case of a 25 year old male patient with a typical clinical carcinoid syndrome. Metastatic carcinoid malignancy was easily diagnosed by very high plasma chromogranin, plasma serotonin and urinary 5-Hydroxy-Indol Acetic Acid levels, and the detection of multiple liver metastases by ultrasound. Somatostatin receptor scintigraphy (SRS) failed to detect the primary lesion, as did upper and lower gastrointestinal (GI) tract endoscopy, bronchoscopy, total body CT, MRI, and GI video tract endoscopy; only F-DOPA PET-scan ascertained and accurately localized the primary ileal tumor. Surgery confirmed the localisation, and pathology revealed a 3 cm highly differentiated carcinoid tumor with low proliferation grade (Ki67<2). The therapy with short and long acting somatostatin analogues was started before surgery and continued after surgical intervention. There was a regression of the clinical carcinoid syndrome and a numerical involution of liver metastases, but the levels of chromogranin A and serotonin remained elevated. Other therapeutical option should be discussed.

Context. In HIV+ patients, several factors related to patient and antiretroviral therapy (ART) could determine early onset of bone mineral density (BMD) disturbances. Objective. Evaluation of bone quality according to gender in patients from the HIV Romanian cohort. Design. A cross-sectional study in “Prof. Dr. Matei Balș” National Institute for Infectious Diseases, Bucharest between 2016-2018. Subject and Methods. We collected data regarding HIV infection, ART history, viral hepatitis co-infections and we calculated patients body mass index (BMI). CD4 cell count, HIV viral load (VL), vitamin-D levels were determined. Dual-energy X-ray absorptiometry (DXA) scans were used to evaluate BMD. Results. We enrolled 97 patients with the median age of 26 years. According to the DXA T-scores, 10 males and 8 females had osteopenia and 4 males and 4 females had osteoporosis. According to Z-scores 2 males and 1 female had osteoporosis. Hip DXA T-scores revealed osteopenia in 6 males and 9 females, whereas T and Z-scores showed osteoporosis in 2 males and 3 females. Lumbar spine (LS) T-score diagnosed osteopenia in 9 males and 6 females, while T and Z-scores revealed osteoporosis in 3 males and females. In males, low T-scores were associated with decreased BMI; low LS DXA Z-scores with low vitamin-D levels; low T and Z-scores and LS-BMD with high VL. Conclusions. Evaluating bone quality in patients with a long history of HIV infection, multiple factors should be taken into account.

Context and objective. Reactive oxygen species (ROS) produced under oxidative stress is important for osteoclastogenesis. As a major member of the metallothionein (MT) family, metallothionein2 (MT2) can scavenge ROS in osteoblasts. However, the role of MT2 in osteoclastogenesis and ROS production in osteoclast precursors (OCPs) is unknown. Material and methods. In this study, we first investigated MT2 expression level in osteoporotic model mice. Next, we explored the roles of MT2 in osteoclastic differentiation and ROS production in OCPs. Ultimately, via rescue assays based on hydrogen peroxide (H2O2), the significance of ROS in MT-2-regulated osteoclastic differentiation was further elucidated. Results. Compared with sham operated (Sham) mice, ovariectomized (OVX) mice displayed bone marrow primary OCPs (Ly6C+CD11b-) having higher ROS levels and lower MT2 expression. MT2 overexpression inhibited the formation of mature osteoclasts, while MT2 knockdown was contrary. Moreover, MT2 overexpression inhibited ROS production in OCPs, while MT2 knockdown exhibited the opposite effects. Notably, the inhibitory effect of MT2 overexpression on osteoclastogenesis and ROS production was blocked by the addition of H2O2. Conclusion. MT2 inhibits osteoclastogenesis through repressing ROS production in OCPs, which indicates that the strategy of upregulating MT2 in OCPs may be applied to the clinical treatment of osteoclastic bone loss.

Objective. To evaluate the effect of multiple daily injection (MDI) treatment replaced by Exenatide BID as compared with continuation of MDI. Patients and Methods. A total of 140 patients with type 2 diabetes, taking metformin and multiple daily insulin injections, were randomized to exenatide or insulin group that continued their insulin treatment. Patients were followed-up for 16 weeks. Blood glucose profiles, BMI, waist circumference, HbA1C, serum lipids and side effects were assesssed at weeks 0,12 and 16. Results. There were no significant differences between the two groups with respect to baseline parameters. Glycemic control was similar between the two groups. The mean changes in HbA1C in exenatide group were -0.66±0.63% and in insulin group -0.74±0.92 % (p=0.594). In exenatide group, 59.6 % of patients and in insulin group 85.71 % of patients had maintained or improved glycemic control at the end of the study. In insulin group, insulin requirement increased 5.86 ± 4.46 units/day. Body weight and waist circumference decreased significantly in exenatide treatment group with respect to insulin group (p<0.001). Conclusions. Substituting exenatide for insulin might be an option in insulin-treated, type 2 diabetic patients having obesity, and poor glycemic control. However, patients with longer duration of diabetes and insulin treatment and with lower C-peptide levels might not benefit from exenatide therapy.

Context. Anethum graveolens L. is used in the treatment of numerous diseases. But there is limited data about the Anethum graveolens efficiency in thyroid tissue. Objective. The aim of this study is to assess the functional and histopathological changes in thyroid tissues from rats treated with Anethum graveolens L. extract. Design. This is an experimental animal study and duration of the study was 30 days. Subjects and Methods. Twenty-eight female Wistar Albino rats were divided into four equal groups. A gavage of Anethum graveolens L. extract at 0, 50, 150 and 300 mg/kg/day doses were given to the rats with 1 mL 0.9% NaCl, respectively, for 30 days. Blood was taken at day 0, 15 and 30. fT3, fT4, TSH values and antioxidant efficiency were observed. Also the thyroidectomy tissue was assessed histopathologically. Results. There is no difference observed in the fT3, fT4 and TSH values of groups 1, 2 and 3 at day 1, 15 and 30 (p>0.05); however, in group 4, TSH value decreased on days 15 and 30 when compared to day 1 and the other groups (p<0.05). Also the hypertrophy and thyroid follicular cell hyperplasia were significantly increased in group 4 (p<0.05). There is no difference in antioxidant efficiency in any of the groups (p>0.05). Conclusion. Anethum graveolens L. extract is effective on both the function and the histology of thyroid tissue but it has no effect on antioxidant status.

Aim. Posttransplant diabetes mellitus (PTDM) is a metabolic complication that usually occurs after liver transplantation (LT) due to immunosuppression. In this study, our aim was to identify PTDM incidence after LT in our center and the potential risk factors. Materials and Methods. In this study, 238 adult LT patients were evaluated in terms of PTDM development. Results. Of 238 patients included in the study, 170 (71.4%) were male, 68 (28.6%) were female and the mean age was 43.5± 13.7 years. Of all patients, PTDM developed in 24 (10.1%). Transient-Hyperglycemia (t-HG) was detected in 31 (13%) patients. PTDM and t-HG patients had a greater body weight than non-PTDM patients (BMI kg/ m2 : 27.6± 5.3, 25.8± 4.3and 23.9± 3.3, respectively p<0.001 p= 0.028). PTDM and t-HG patients mean age was higher than non-PTDM patients (51.5± 9.68, 48.2± 11.1 and 41.5± 14 years, respectively, p= 0.002 p= 0.023). In the univariate analysis, the only independent risk factor for PTDM was age (OR 1.93, 95% CI 1.31-2.97). Conclusion. Age is the most important risk factor for PTDM development after LT. PTDM was found more common in the patient group with greater body weight. Patients with older age and greater body weight should be examined more carefully for PTDM before LT.

Introduction. Insulin resistance or dysfunction of pancreatic beta cells represents one of the important worldwide endocrine disease challenges. In fact, vascular endothelial dysfunction (VED) is involved in the pathogenesis of one of the most significant causes of diabetes-induced morbidity; diabetic nephropathy (DN). Asymmetric dimethyl arginine (ADMA) is one among other incriminating mechanisms of VED. The aim of this study was to assess whether ADMA modulation could be achieved by taurine or rosiglitazone, and whether they could improve tubulo-interstitial ischemia and subsequent renal damage in experimental DN in rats. Material and methods. 40 male Wistar rats were randomly assigned into 4 groups: normal saline-injected control, diabetic control induced by intraperitoneal injection of streptozotocin (STZ) (45 mg/kg), and two diabetic groups daily treated orally with rosiglitazone (3 mg/kg) and taurine (500 mg/kg) respectively, for 12 weeks after STZ injection. Results. Both rosiglitazone and taurine treatments significantly decreased fasting blood glucose, renal functions (serum creatinine, blood urea nitrogen, albuminuria), and renal oxidant potential (Malondialdehyde), as well as, tumor necrosis factor-alpha (TNF-α). They also significantly improved renal antioxidant capacity (reduced glutathione) and histopathological changes. Furthermore, taurine significantly diminished serum ADMA, while rosiglitazone showed no significant effect. Conclusion. The present study suggests that the treatment with rosiglitazone or taurine can reduce the progression of renal damage in streptozotocin-induced diabetic nephropathy in rats by different mechanisms. However, reducing ADMA could be a potential therapeutic target.

Context. Human zonulin is a protein that regulates the intercellular tight junctions in various tissues and organs of the human body. Hashimoto’s thyroiditis (HT) is one of the most common endocrine autoimmune disorder, but the role of increased intestinal permeability in its pathogenesis is still being studied. Objective and design. This pilot cross-sectional study investigates serum zonulin concentration in adults with Hashimoto’s thyroiditis and assesses the relationship between zonulin levels, clinical hormonal and immunological characteristics. Subjects and methods. A group of 62 adults with HT participated in this study and were divided into three groups: hypothyroid (n=33) euthyroid (n=25) and hyperthyroid (n=4). Serum zonulin was determined using an ELISA method. Results. Age, gender and BMI were different between groups (hypothyroid and euthyroid ones). Serum zonulin values ranged from 2.6 to 198.0 ng/mL in participants. A direct positive correlation was found between serum zonulin levels and weight and BMI (r = 0.351, p = 0.008 and r = 0.236, p = 0.05, respectively). Conclusions. There is no correlation between zonulin and thyroid hormones or autoantibodies in Hashimoto thyroiditis patients. There is a difference in zonulin levels between the studied groups, but they are not statistically significant.

The hemostatic balance is a complex system where the delicate equilibrium is regulated by several factors including hormones. Hypothyroidism, as a common disease in the general population, affects both the coagulation and fibrinolytic systems. However, the reliable clinical evidence is so far lacking and published data remain conflicting. According to the severity of the disease, we divided all study subjects into four groups: 50 controls, 47 patients displaying subclinical hypothyroidism, 41 patients displaying moderate hypothyroidism (TSH≤50 mU/L), and 53 patients displaying severe hypothyroidism (TSH>50 mU/L). We investigated various coagulation parameters including: activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FIB) and international normalized ratio(INR). Compared with control subjects, patients with subclinical hypothyroidism displayed hypercoagulability, as reflected by shorter APTT levels and increased FIB levels. The patients with moderate hypothyroidism had only increased TT levels without any significant variation in the other studied parameters, which suggested neither obvious bleeding tendency nor clotting tendency. The patients with severe hypothyroidism displayed a bleeding tendency, as reflected by higher APTT, PT, TT, INR levels and decreased FIB levels. The patients with different hypothyroidism stages display various abnormalities of coagulation.

Autoimmune diseases are a heterogeneous group that involves almost any tissue and organ, a patient could frequently present more than one autoimmune disease. Type 1 diabetes mellitus is frequently associated with other autoimmune diseases in polyglandular autoimmune syndrome. Aim of the study is to evaluate a phenotype of diabetic patients with autoimmune diseases. There is a retrospective study; we analyzed type 1 diabetes inpatients from our department in late 4 years based on clinical records. We state that type 1 diabetes mellitus diagnosis is established based on insulin treatment at onset or less than 1 year from onset. We analyzed the presence of the following autoimmune diseases: Graves&#8217; disease, Hashimoto thyroiditis, autoimmune hypothyroidism, Addison&#8217;s disease, vitiligo, psoriasis, systemic lupus erythematosus, pernicious anemia. We recorded 151 patients with type 1 diabetes mellitus: 91 (60.3%) women. Mean age was 38.4?15.8 years, mean span of type 1 DM was 12 years, mean age at the onset of DM was 26.5 years, and mean BMI was 23.4 kg /m2. Patients were insulin treated with 2 doses of insulin 11.3%, 3 doses of insulin 41.6%, 4 doses of insulin 45%, and insulin pump 2%. 41 patients (27.2%) associated other autoimmune diseases, most frequently being chronic thyroiditis. Type 1 DM preceded autoimmune disease in 60%. Patients that associated autoimmune disease have mean age at the onset of type 1 DM 29.1 years. Mean glycated hemoglobin among patients with autoimmune diseases was 10.1% vs. 9.9% among patients without autoimmune diseases (NS); mean insulin needs were respectively 0.78 u/kgc vs. 0.72 u/kgc (NS). In conclusion, type 1 DM is frequently associated with other autoimmune diseases, patients being mainly women. The most frequent association is Graves&#8217; disease. In over 50% of cases type 1 DM precedes autoimmune disease with several years. Even though more than half of patients were treated with multiple doses of insulin, glycated hemoglobin was high, slightly higher among patients with autoimmune diseases but the differences were not statistically significant.