Cardiovascular evaluation and endothelial dysfunction in Cushing syndrome following remission: a prospective study.

PURPOSE: Cushing syndrome (CS) is a well-known risk factor for cardiovascular morbidities. We aimed to evaluate endothelial and cardiovascular functions, endothelial mediators and pro-inflammatory cytokines in patients with CS before and after remission. METHODS: Adult patients with newly diagnosed endogenous CS were included. Metabolic [body mass index (BMI), glucose, and lipid values] and cardiovascular evaluation studies [24-h ambulatory blood pressure monitoring, carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), and echocardiography] were performed, and endothelial mediators [asymmetric dimethyl arginine (ADMA) and endothelin-1 (ET-1)] and pro-inflammatory cytokines [interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α)] were measured. Control group was matched in terms of age, gender, and BMIs. RESULTS: Twenty-five patients, mean age 40.60 ± 14.04 years, completed the study. Compared to controls (n = 20) mean arterial pressure (MAP) and CIMT were higher (p < 0.005 and p = 0.012, respectively), and FMD (p < 0.001) and mitral E/A ratio (p = 0.007) lower in the patients during active disease. Baseline serum ADMA, ET-1, and IL-1ß were similar between the groups, while TNF-α was lower in the patients (p = 0.030). All patients were in complete remission 1 year following surgery. BMI, LDL cholesterol, serum total cholesterol, fasting plasma glucose, MAPs, and CIMT significantly decreased (p < 0.005), while there was no improvement in FMD (p = 0.11) following remission. There was no significant change in ADMA, IL-1ß, and TNF-α levels, but ET-1 increased (p = 0.011). CONCLUSIONS: Remission in CS improves some cardiovascular parameters. ADMA and ET-1 are not reliable markers for endothelial dysfunction in CS. Metabolic improvements may not directly reflect on serum concentrations of TNF-α and IL-1ß following remission of CS.

HIGH THYROPEROXIDASE ANTIBODY TITERS MAY PREDICT RESPONSE TO ANTITHYROID DRUG TREATMENT IN GRAVES DISEASE: A PRELIMINARY STUDY.

Background and aim: Antithyroid drugs are first treatment for Graves hyperthyroidism worldwide. Although remission can be achieved in approximately 40-50% of patients in 12-18 months with antithyroid drugs, this period can be extended up to 24 months. We aimed to evaluate the effect of individual clinical/biochemical variables and GREAT score in predicting response to antithyroid drug in Graves disease. Material and methods: This is a retrospective single-center study including 99 patients with the first episode of Graves disease treated for at least 18 months. The patients were classified into two groups as those who responded to antithyroid medication at 18-24 months (group 1) and those who did not respond at 24 months and continued with low-dose antithyroid medication (group 2). Results: Medical treatment response was obtained in 38 (38.3%) of the patients at 18 months, and in 19 (19.1%) patients at 24 months. Long-term medical treatment (>24 months) was given to the remaining 43 patients due to the lack of response to medical treatment. Thyroid volume and free T4 levels were higher in those followed up with long-term antithyroid drugs, and orbitopathy was more common in this group. Median anti TPO value was significantly higher in group 1 when compared to group 2 (593 U/l and 191.6 U/l respectively). More patients were classified as GREAT class 3 in group 2 when compared to group 1 (46.5% and 12,5% respectively). We analyzed the Thyroperoxidase Antibody(anti TPO) titers, which we divided into three levels, according to groups 1 and 2. Post-hoc Chi-Square analysis revealed that falling into the highest anti TPO category was significantly associated with response to medical therapy in 24 months (p <0.05). Conclusion: According to our study, GREAT score and anti TPO Ab titers at presentation may help predict response to ATD in Graves disease.

Metabolic role of hepassocin in polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a female endocrinopathy characterized by hyperandrogenemia, insulin resistance, glucose intolerance, dyslipidemia, non-alcoholic fatty liver disease (NAFLD), and obesity. Hepassocin (HPS) is a hepatokine involved in energy and lipid metabolism. We aimed to investigate the role of HPS in metabolic dysfunction and its relationship with fatty liver in patients with PCOS. PATIENTS AND METHODS: A total of 45 newly diagnosed PCOS patients and 42 healthy women of similar age were included in the study. Routine anthropometric, biochemical, and hormonal information were recorded. Serum HPS and high-sensitivity C-reactive protein (hsCRP) were measured, and NAFLD fibrosis score (NFS) and Fibrosis-4 (FIB-4) were calculated and correlated. RESULTS: HPS and hsCRP values of the PCOS group were found to be significantly higher than controls (p=0.005, p<0.001, respectively). A positive correlation was found between both HPS and hsCRP and luteinizing hormone (LH) (p<0.001). No correlation was observed between HPS and NFS and FIB-4, however, only a weak negative correlation was observed between hsCRP and FIB-4. A negative correlation was found between HPS and BMI, waist circumference, fat ratio, and HbA1c (p<0.05). In multivariate regression analysis for HPS, R-squared is 0.898, and hsCRP, neck circumference, fat amount, and LH are significant factors. CONCLUSIONS: NAFLD is an important dysmetabolic component of PCOS. Serum HPS is elevated in PCOS patients. We found a positive correlation between hsCRP and LH and a negative correlation between obesity indices, although we did not find an association between NFS and FIB-4, and HPS. In the future, large-scale molecular studies of HPS may be beneficial.

Sonographic evaluation of subclinical entheseal involvement in patients with hypoparathyroidism: a case control study.

PURPOSE: Hypoparathyroidism is a disease characterized by low serum calcium, increased serum phosphorus and low PTH levels. Although patients are treated with active vitamin D and calcium, a proper serum calcium phosphorus balance cannot always be achieved. Ectopic calcifications that develop in organs during treatment are the most common complications. To date, there is not any published study on enthesopathy in patients with hypoparathyroidism. The aim of this study was to evaluate subclinical enthesopathy in patients with hypoparathyroidism with ultrasound and to compare the results with those of the control group. METHODS: The study included patients aged 18-65 years with postoperative hypoparathyroidism and hypothyroidism (group hypoP + hypoT), patients with postoperative hypothyroidism (group hypoT), and healthy age and sex-matched volunteers (group C). Ultrasonographic findings of enthesopathy in both extremities were documented according to the Glasgow Ultrasound Enthesitis Scoring System (GUESS). RESULTS: GUESS scores in group hypoP + hypoT, were significantly higher when compared to the other groups. There was a statistically significant correlation between the total GUESS scores and total enthesophyte scores and the duration of hypoparathyroidism (p < 0.05, r = 0.43) (p < 0.05, r = 0.39) respectively. In the correlation analysis of all groups, a significant negative correlation was found between serum Ca and PTH levels and the total GUESS scores (p < 0.01, r = - 0.37; p < 0.01, r = - 0.54, respectively). CONCLUSION: This study showed that GUESS scores were significantly higher in patients with hypoparathyroidism compared to those with hypothyroidism and control subjects. GUESS scores were positively correlated with disease duration. Patients with hypoparathyroidism need to be evaluated for subclinical enthesopathy during follow-up.

A CASE OF HYPONATREMIA DUE TO PITUITARY METASTASIS OF LUNG CANCER.

Context: Hyponatremia is a common electrolyte abnormality. Objective: We report a patient who presented with hyponatremia and diagnosed as small cell lung cancer metastatic to hypothalamus and pituitary. Case report: A 68 year old male patient was admitted with fever and cough and pneumonia was considered. Serum sodium level was 113 mmol/L. Syndrome of inappropriate ADH (SIADH) is considered. Thyroid function tests and cortisol levels pointed out a central deficiency in both axes. Pituitary MRI was performed and a hypothalamic and pituitary mass were observed. Prednisolone therapy was started followed by L thyroxine replacement. A chest computer tomography (CT) was taken 2 weeks later revealed a mass lesion. Bronchoscopic biopsy was performed and histopathological diagnosis of the tumor was reported as small cell lung cancer. Result: Many mechanisms were considered as the cause of hyponatremia in our patient. SIADH, secondary adrenal insufficiency and secondary hypothyroidism due to pituitary metastasis are possible causes. Conclusion: The reason of hyponatremia is sometimes complex. When the underlying causes of hyponatremia are not evaluated in detail, many diagnoses can be missed.

Association of blood pressure with dietary intake, physical activity, and anthropometric measurements in Turkish adolescents.

BACKGROUND: Determining high blood pressure in childhood is an important step to reduce the risk of occurrence of high blood pressure-related diseases in adulthood. AIMS: This study aimed to assess the association of blood pressure with dietary intake, physical activity, and anthropometric measurements in Turkish adolescents. PATIENTS AND METHODS: This cross-sectional study included 370 students (202 females, 168 males) aged 14 to 18 years from one private and one public school in Kayseri, Turkey. Some anthropometric measurements and 24-hour dietary recall of the students were obtained. Their blood pressures were measured, and the International Physical Activity Questionnaire and the Mediterranean Diet Quality Index (KIDMED) were used. RESULTS: The body mass index (BMI) mean and waist/height ratio of the hypertensive group were significantly higher than those of the prehypertensive group, whereas their daily potassium, calcium, and magnesium intakes were significantly lower than those of the normotensive group. The percentage of individuals with very low diet quality was higher in the hypertensive group than in the normotensive group (P > 0.05). The percentage of participants with sufficient physical activity was higher in the normotensive group than in the prehypertensive and hypertensive groups. CONCLUSION: Factors such as high BMI and waist/height rates; low calcium, magnesium, and potassium intakes with diet; insufficient physical activity; and low quality of diet might cause an increase in the blood pressure.

Molecular skin changes in Cushing syndrome and the effects of treatment.

OBJECTIVE: We investigated newly diagnosed patients with endogenous CS for molecular changes in skin by biopsy before and a year after treatment of CS. PATIENTS AND METHODS: 26 Patients with CS and 23 healthy controls were included. All the patients were evaluated before and a year after treatment. Skin biopsies were obtained from abdominal region before and a year after treatment in patients with CS and once from healthy volunteers. Total RNA was isolated from the skin biopsy samples and the real-time PCR system was used to determine the expression levels of 23 genes in the skin biopsy. RESULTS: Skin expression levels of HAS 1, 2 and 3 mRNAs were lower and COL1A2, COL2A1, COL3A1 mRNAs were higher in patients with CS than in normal controls. MMP-9, TIMP-1 and elastin mRNA expression levels were similar in two groups. Skin IL-1ß mRNA expression level was significantly higher in patients with CS. None of these parameters changed significantly 12 months after treatment. Patients with CS showed higher skin GH and HSD11B1 mRNA expressions and lower GHR and IGF-1R mRNA expression compared to control. Expression levels of IGF-1, GR and HSD11B2 mRNA were similar in two groups. None of these parameters changed significantly 12 months after treatment. CONCLUSION: CS is associated with increased expression levels of skin COL1A2, COL2A1, COL3A1 mRNAs (which are correlated with increased expression level of skin GH mRNA). Decreased skin HAS may cause decreased synthesis of HA that contributes to thinning of skin in CS. Increased local inflammatory cytokine and HSD11B1 mRNAs may be related to the acne formation in CS. Treatment of CS was not able to reverse these changes and ongoing changes were detected after treatment.

Factors that affect the Glycemic Control Achieved by Switching to Insulin Degludec/ Aspart in Insulin-Treated Patients with Type 1 and Type 2 Diabetes in a Real-World Setting: a Non-interventional, Retrospective Cohort Study.

BACKGROUND: Insulin degludec/aspart (IDegAsp) is a co-formulation with IDeg and IAsp. Different insulin regimens may be switched to IDegAsp. In this study, we aimed to find out the effect of switch to IDegAsp on glycemic control and whether the basal characteristics and treatment modalities of the patients affect the change in glycemic control brought by switch to IDegAsp. METHODS: We retrospectively analyzed the records of 78 patients whose insulin therapies (basal+bolus, premixed analogues or basal only) were switched on a 1:1 unit basis to IDegAsp±bolus insulin. Oral antidiabetic agents (OADs) given were recorded. At the end of 12th and 24th week, total insulin doses of patients and HbA1c were compared to the baseline. RESULTS: There was a statistically significant decrease at HbA1c at 12 weeks (1.4%; p<0.001). There was not a significant difference in HbA1c between the OAD added group and the group with no new OADs(p=0.1). Basal insulin dose was not statistically different from baseline, whereas bolus insulin dose was significantly lower (p=0.007). At the end of 24 weeks the decrease in HbA1c level from baseline was preserved. CONCLUSION: Regardless of the baseline insulin regimen, diabetes type and oral antidiabetic drugs given, HbA1c is significantly lowered after switching to IDegAsp.

ABDOMINAL BIOELECTRIC IMPEDANCE FOR FOLLOW-UP OF DIETERS: A PROSPECTIVE STUDY.

CONTEXT: Visceral adipose tissue (VAT) is a strong predictor of carbohydrate metabolism disorders. Abdominal bioelectrical impedance analysis (A-BIA) is a simple method for the measurement of VAT and is a promising tool in screening and follow-up of abdominal obesity. However the role of A-BIA in dieting individuals has not been evaluated adequately in longitudinal follow-up studies. OBJECTIVE: The aim of this study is to determine the role of A-BIA in identifying the changes in metabolic predictors after diet and/or exercise therapy. DESIGN: All patients who sought weight loss treatment underwent baseline assessment and were prescribed a program of diet. After a mean follow-up of 3.2 months, data were analyzed. SUBJECTS AND METHODS: Ultimately, 103 participants who reported adhering to the diet, enrolled to the study. We tested associations between changes in body composition measures and changes in laboratory measures using correlations and multivariate linear regression analysis. RESULTS: Mean loss of body weight was 3.4±2.8 kg. All but waist-to-hip ratio, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels changed significantly (p<0.001). Decreases in body weight, body mass index (BMI), and VAT level significantly correlated with decreases in fasting blood glucose, fasting insulin level, and HOMA-IR score (r=0.230-0.371). In multiple linear regression analysis changes in BMI and VAT significantly correlated with change in HOMA-IR score (F(7.93)=2.283, p=0.034, R2=0.147). CONCLUSION: Decreases in BMI and VAT, as determined by A-BIA, were predictors of changes in metabolic laboratory measures. A-BIA is useful for follow-up of patients receiving diet therapy for weight loss.

SU-E-T-438: Optimal Proton Beam Energy to Treat Adult CNS, Adult Head and Neck, and Pediatric Cancers.

PURPOSE: Proton therapy machines with lower beam energy requirements are expected to be easier and more cost-efficient to design, construct, and operate, particularly when using novel proton acceleration technology (e.g., dielectric wall). We determine, for adult central nervous system (CNS) and head and neck (HN) and pediatric cases, the optimal proton beam energies that can lead to clinically acceptable plan quality. METHODS: Proton treatment plans for various adult CNS and HN and pediatric cases, previously treated at our institution using helical tomotherapy, were generated using a commercial planning system (XiO, v. 4.62, Elekta) with a passively-scattered proton beam model. Proton beam orientations were chosen such that the distance from the skin to the distal target edge was minimal; however, beams could not pass through areas with significant surface irregularity (e.g. ear), nor through OARs with strict dose limitations (e.g. lens). For a given beam direction, the planning system would calculate an optimum range and modulation to cover a given target volume. Beam weights were adjusted so that 95% of the target volume received the prescribed dose. All plans were limited to two proton beams. RESULTS: An optimal proton energy exists for each case studied. Among all cases, target dose conformity (the ratio of target volume to volume encompassed by theprescribed dose) ranged from 0.74 to 0.94, and target dose uniformity (the ratio of the D5 and D95 doses) ranged from 1.01 to 1.04, with the optimal proton energies. Among the CNS and HN cases and for most pediatric cases, the maximum proton energy required was 133 MeV. For a pediatric abdomen case, 159 MeV protons were required. CONCLUSIONS: For protontreatment of most adult CNS and HN and pediatric cases, the optimal energies that are capable of generating good quality plans are only as high as 130 MeV.

The effects of Gingko biloba, vitamin E and melatonin on bacterial translocation in thioacetamide-induced fulminant hepatic failure in rats.

BACKGROUND AND STUDY AIMS: Bacterial translocation (BT) has been implicated in the development of infectious complications in many serious clinical conditions such as fulminant hepatic failure (FHF). We aimed to investigate the effects of Gingko biloba (GB), vitamin E (Vit E) and melatonin on intestinal oxidative damage and BT in thioacetamide (TAA)-induced FHF in rats. MATERIALS AND METHODS: A total of 42 rats were divided into five groups. Group 1 (n = 8) was the control group. Group 2 (n = 10) was the TAA group, in which rats received 350 mg/kg TAA daily by the intraperitoneal (ip) route for 3 days. Oral 100 mg/kg GB per day was administered to group 3 (n = 8), oral 200 mg/kg Vit E per day to group 4 (n = 8) and ip 3 mg/kg melatonin per day to group 5 (n = 8) 48 h prior to the first TAA injection and was continued for 5 consecutive days. RESULTS: When compared with the control group, serious hepatic and intestinal oxidative damage, increased Escherichia coli counts in ileal aspirates and high BT frequencies were observed in the TAA group (all p < 0.0001). Only GB treatment attenuated hepatic oxidative damage (p < 0.0001). There was no difference in intestinal oxidative damage, E. coli counts in ileal aspirates and BT frequency between TAA and the other antioxidant treatment groups (p > 0.05). CONCLUSION: Our results suggest that intestinal oxidative damage plays a major role in the development of BT by disrupting the barrier function of intestinal mucosa.

Protective effects of Gingko biloba on thioacetamide-induced fulminant hepatic failure in rats.

Gingko biloba (GB) has antioxidant and platelet-activating factor (PAF) antagonistic effects. We investigated the protective effects of GB on thioacetamide (TAA)-induced fulminant hepatic failure in rats. Fulminant hepatic failure was induced in treatment groups by three intraperitoneal (ip) injections of TAA (350 mg/kg) at 24-hour intervals. Treatments with GB (100 mg/kg per day, orally) and N-acetylcysteine (20 mg/kg twice daily, sc) were initiated 48 hours prior to TAA administration. The liver was removed for histopathological examinations. Serum and liver thiobarbituric acid-reactive substance (TBARS) levels were measured for assessment of oxidative stress. Liver necrosis and inflammation scores and serum and liver TBARS levels were significantly higher in the TAA group compared to the control group (P < 0.001, < 0.001, 0.001, < 0.001, respectively). Liver necrosis and inflammation scores and liver TBARS levels were significantly lower in the GB group compared to the TAA group (P < 0.001, < 0.001 and 0.01, respectively). GB ameliorated hepatic damage in TAA-induced fulminant hepatic failure. This may be due to the free radical-scavenging effects of GB.

Fine needle aspiration biopsy of thyroid nodules.

BACKGROUND: Fine needle aspiration biopsy (FNA) is a routine diagnostic technique for evaluating thyroid nodules. Many reports in adults consider that FNA is superior to thyroid ultrasonography (USG) and radionuclide scanning (RS). Only five studies have been published on FNA of childhood thyroid nodules. AIMS: To investigate the reliability of FNA in the evaluation and management of thyroid nodules, and compare the results of FNA, USG, and RS with regard to final histopathological diagnosis. METHODS: FNA was performed in 46 children with thyroid nodules after USG and RS examination. We investigated the sensitivity, specificity, accuracy, and positive and negative predictive values of USG, RS, and FNA in their management. RESULTS: Six patients who had malignant or suspicious cells on FNA examination underwent immediate surgery. The other 40 patients received medical treatment according to their hormonal status. Fifteen of these nodules either disappeared or decreased in number and/or size. Surgery was performed in 25 patients who did not respond to therapy. Statistical analysis revealed sensitivity, specificity, accuracy, and positive and negative predictive values respectively as follows: 60%, 59%, 59%, 15%, and 92% for USG; 30%, 42%, 39%, 12%, and 68% for SC; 100%, 95%, 95%, 67%, and 100% for FNAB. CONCLUSION: FNAB is as reliable in children as in adults for definitive diagnosis of thyroid nodules. Using this technique avoids unnecessary thyroid surgery in children.

Selective irradiation for the treatment of recurrent ovarian carcinoma involving the vagina or rectum.

OBJECTIVE: The aim of this study was to evaluate the role of selective irradiation in the management of recurrent or persistent ovarian carcinoma involving the vagina or rectum after initial surgery or surgery and chemotherapy. METHODS: Twenty-eight patients with recurrent or persistent vaginal and/or perirectal disease from ovarian carcinoma received selective irradiation and were evaluated for local control, survival, and quality of life. Seventy-nine percent had previously received various combinations of chemotherapy after initial surgery. At recurrence, 68% of the 28 patients were treated with external beam irradiation only, 7% with brachytherapy only, and 18% with both external beam irradiation and brachytherapy. In addition, 50% of the patients received various combinations of chemotherapy before or after radiotherapy and 3 patients received additional surgery. RESULTS: Vaginal bleeding was controlled in all patients and a complete symptomatic response was achieved in 79% of the symptomatic patients. Survival after recurrence at 2 years was 57% for patients who had no liver or extra-abdominal metastasis at the time of radiotherapy (21 patients) and 0% for patients who had liver or extra-abdominal metastases (7 patients). Median survival of 5 patients with abdominal and pelvic disease and 16 patients with no extrapelvic disease at the time of recurrence was 2.16 (0.16-10.67) and 2.08 (0.58-27) years, respectively, after recurrence. Fifty percent of the 16 patients without extrapelvic disease had a complete response to radiotherapy (CR group) and the remaining had a partial response or stable disease (non-CR group). The 1-year survival after salvage irradiation in this same group was 100% in the CR group and 37.5% in the non-CR group (P < 0.0001). There are 4 long-term survivors in the CR group who are still alive in excess of 5 years after salvage radiotherapy. Thirty-five percent (5/14) of the patients with pelvic disease only recurred in the unirradiated upper abdomen. CONCLUSIONS: Radiation can be considered an effective treatment option for patients with vaginal and/or perirectal recurrences of ovarian carcinoma. It offers excellent palliation to patients with disseminated disease and may result in both local control and long-term survival in patients with nondisseminated disease. This location may represent a sanctuary site from chemotherapy. Pelvic irradiation alone may be effective salvage and the addition of brachytherapy may improve local control, particularly in patients with disease confined to the pelvis who undergo debulking or chemotherapy.

Increased serum leukotriene B4 level in the active stage of rheumatoid arthritis in children.

The possible association of leukotriene B4 (LTB4)-like activity with the development of active rheumatoid arthritis was studied in 25 children with the disease and in 15 normal subjects. Serum LTB4-like activity was found to be significantly higher in the active stage of the disease when compared with the values obtained from patients during the inactive stage and from healthy children. No correlation was found between LTB4-activity and other laboratory parameters, e.g. haemoglobin level, white cell count and erythrocyte sedimentation rate.

Maternal lymphocyte subsets in the cases with neural tube defects.

Neural tube defects (NTDs) are among the most prevalent of congenital malformations. Organ system anomalies and certain changes in the thymus gland have also been reported. Lymphocyte subset changes can be expected in infants with NTD as a result of these thymic anomalies. We investigated lymphocyte subpopulations in twenty-one mothers of NTD cases in order to evaluate the maternal immunological alterations. The mothers of twenty-one healthy infants were chosen as a control group. Pregnancy is known to be associated with a depression in cellular immunity. We found, however, some additional changes in cellular immunity in the mothers of NTDs. The CD4/CD8 ratios were significantly lower than those of control mothers (p = 0.044). This difference was related to the increased percentage of CD8 cells found in mothers of NTDs (p = 0.004). These results suggest that immunosuppression is more evident in the mothers of babies with NTDs.

Low-dose sultamicillin oral suspension in the treatment of mild to moderate paediatric infections in Turkey.

A total of 101 children (47 males, 54 females; age range, 3 months-16 years) with mild to moderate upper or lower respiratory tract infections, or skin and soft tissue infections entered a clinical study conducted at two centres in Izmir, Turkey. The children received a mean daily dose of 25 mg/kg sultamicillin oral suspension administered as two equal doses approximately 12 h apart. In total, 100 children met all requirements for evaluability and were included in the clinical efficacy assessment, and 49 children were evaluated for bacteriological efficacy. Clinical cure was reported by the investigators in 93 patients, improvement in six and failure in only one. The bacteriological eradication rate of isolated pathogens was 100%. Of the 101 patients evaluated for drug safety, four experienced adverse drug-related or possibly drug-related reactions. All side-effects were gastro-intestinal and diarrhoea was reported in three patients. No discontinuation of therapy was reported, nor were any significant laboratory abnormalities recorded.