ACTA ENDOCRINOLOGICA (BUC)

Abstract. Preeclampsia is a widespread vasospasm and vascular endothelial dysfunction that usually occurs after 20 weeks gestation. Uterine artery Doppler is a good sensitive predictor. PP13 (as a chemical predictor) was claimed to provide similar results. Objective. To evaluate whether first trimester maternal serum placenta protein 13 (PP13) and the second trimester uterine artery Doppler pulsatility index can predict pre-eclampsia among high risk Egyptian pregnant females. Design. The study took place in obstetric clinic of Kasr Elaini Hospital (Faculty of Medicine - Cairo University) in the period October 2011 - August 2012. Subjects and Methods. The study included 59 pregnant women (11- 13 weeks), 34 normal controls and 25 women at increased risk of developing pre-eclampsia. PP13 was assayed using enzyme-linked immunosorbent assay. Uterine artery Doppler flow velocimetry was done at 22–24 weeks to measure the mean pulsatility index (PI). PP13 multiples of median (MoM) were calculated.PP13 and Uterine artery Doppler PI were compared between women who developed pre-eclampsia and controls. Results. Levels of PP13 were not found to differ between control and affected pregnancies. PP13 MoMs for controls and pre-eclampsia cases were 1.000 (0.516) and 1.7200 (0.851), respectively (P=0.4). PI was significantly higher in affected cases 1.62(0.2) compared to controls 1.24(0.2) (P <0.001). Conclusion. Screening test based only on maternal history or PP13 testing is inefficient in predicting preeclampsia in high risk females. Abnormal uterine artery Doppler velocimetry between 22 and 24 weeks of gestation is still the best test for identification of patients destined to develop preeclampsia.

Context. Childhood cancer survival has increased substantially over the past few decades. However, long-term side effects associated with cancer treatment have also risen. Especially thyroid gland disorders are common. Objective and Design. The present retrospective cross-sectional study aimed to investigate risk factors of long-term TD in survivors of leukemia-lymphoma. Subjects and Methods. The study included 44 acute lymphoblastic leukemia (ALL) and 26 Hodgkin lymphoma survivors (HL). Abnormal laboratory and pathological ultrasonographic findings of the thyroid gland were accepted as a thyroid disorder. The possible causes of thyroid disorders were investigated. Results. Long-term thyroid disorder was found in 40% of the patients. This rate was higher in HL patients than in ALL (65% vs. 25%). Thyroid disorder was significantly more common in patients who received radiotherapy to the neck (57% vs. 17%). Radiotherapy to the neck area was the only significant determinant for thyroid disorders in the regression models [OR 33.17, 95% CI (2.76-398.9) p = 0.006]. However, HL remained significantly associated with TD in the logistic model performed using cancer type [OR 19.25, 95% CI (2.39-155.3) p = 0.006]. Conclusions. The study showed that radiotherapy applied to the neck was an essential risk factor for long-term TD in the average 6-year follow-up of cancer survivors. However, we recommend that childhood cancer survivors should be followed closely for a long time since long-term endocrine side effects were reported during longer than six years follow-up periods.

Objectives. Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that is linked with increased circulating markers of oxidative stress and lowgrade inflammation. The link between inflammation and MetS is not yet fully understood. We aim to evaluate the relationship between the levels of pro and anti-inflammatory markers such as apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), interleukin (IL) 6, tumor necrosis factor alpha (TNF-α), fibrinogen and complement component 3 (C3) and adiponectin and MetS/MetS components. Methods. This study was a case-control study conducted in an outpatient internal medicine clinic of the Ondokuz Mayıs University Internal Medicine Department. A total of 108 subjects (59 female, 49 male) who were not under any dietary restrictions and older than 17 years were selected and divided into two groups (54 with MetS and 54 healthy controls). Results. Increased levels of IL-6, C3 and Apo-B/ Apo-A1 ratios and decreased levels of Apo-A1 and TNF-α (except in patients with hypertriglyceridemia) were detected in the MetS group. Apo-A1 and TNF-α exhibited decreased levels, and IL-6, fibrinogen, C3 and Apo-B levels and Apo-B/Apo-A1 ratios increased as higher numbers of MetS criteria were met in the total study group. Conclusions. We found that inflammatory marker levels were not affected by an increased number of MetS criteria met in the MetS group although these levels increased in the control group with higher numbers of MetS components. The presence of a high number of MetS components does not have an additive pro-inflammatory contribution for subjects already diagnosed with MetS.

Background. Probiotic fermented milk is one of the most beneficial foods. The main purpose of this study was to investigate the effect of probiotic fermented milk on the serum level of insulin and homocysteine in the type 2 diabetes patients. Methods. This study was done in 60 patients with type 2 diabetes. The intervention group received 600 mL of probiotic fermented milk (kefir) daily and control group received 600 mL of conventional fermented milk daily for 8 weeks. Food intake, anthropometric indices, serum parameters were assessed at the beginning and at the end of the study. The statistical analysis was done by the use of SPSS software (Ver.13). Results. The mean of serum insulin level did not reduce significantly after the intervention in probiotic fermented milk group, and there was no significant difference between the two groups. The mean of HOMA-IR decreased significantly in probiotic fermented milk group after intervention and there was a significant difference between the two groups after intervention. The mean of quickie increased in probiotic fermented milk group, but this increase was not significant. Also, there was not significant difference between the two groups after intervention. The mean of homocysteine level decresead significantly in patients with probiotic fermented milk and conventional fermented milk consumption. Conclusions. By considering the effect of probiotic fermented milk on some risk factors of cardiovascular disease in diabetic patients, probiotic foods may be useful as an adjuvant therapy in diabetic patients.

Background: Salivary monitoring of hormone levels has many advantages over the more conventional serum/plasma analysis. Salivary free metanephrines (MN) and normetanephrines (NMN) could precise biochemical diagnosis of pheochromocytoma (PHEO) as an alternative to plasma metabolites.\r\nSubjects and methods: The prospective case-control study included a group of 30 patients confirmed with PHEO an age-matched control group of 70 normotensive subjects. The PHEO diagnosis was suspected on clinical ground and confirmed by imaging studies and classical neuroendocrine markers. Free plasma and salivary NMN and MN were assayed using enzyme immunoassay for both metabolites.\r\nResults: In tumor cases all metabolites were increased. As expected, values for all 4 parameters (mean?SEM) differed significantly in tumor group vs. normal group: free plasma\r\nnormetanephrines (NMNp): 1514.16 ? 282.97 pg/mL vs 47.82?2.52 pg/mL; free salivary normetanephrines (NMNs):\r\n663.63?168.47 pg/mL vs 44.98? 2.47 pg/mL; free plasma metanephrines (MNp): 445.20 ? 99.92 pg/mL vs 18.87?1.03\r\npg/mL; free salivary metanephrines (MNs):206.60?91.48 pg/mL vs 14.47?0.72 pg/mL with significant correlations in all\r\n100 subjects. Passing & Bablok regression showed no significant deviation from linearity in Elisa assay of NMNs vs NMNp; a significant deviation from linearity existed\r\nin Elisa assay of MNs vs MNp. Cut-off values, sensitivity and specificity for all 4 parameters were calculated by ROC\r\nanalysis. Plasma and salivary normetanephrines proved similar sensitivity (100%) and specificity (100%). Pairwise\r\ncomparison of ROC curves areas showed no significant differences between NMNp vs NMNs and MNp vs MNs. Ten cases were investigated post-surgery. All 4 parameters\r\nshowed no significant differences vs. control group.\r\nConclusions: Salivary free normetanephrines could be used as a nonstressful marker for diagnosis purpose in pheochromocytoma proving similar sensitivity and specificity as plasma free normetanephrines.

Introduction. The determination of phenylalanine (Phe) and tyrosine (Tyr) levels in blood plasma is very important not only in early diagnostic, but also in monitoring the treatment of phenylketonuria (PKU). Purpose. We present a simple, sensitive and accurate procedure to determine simultaneously the plasma concentrations of Phe and Tyr. Procedure. The measurement involves two steps: a) separation of plasma (from blood prelevated on heparin), isolation and preparation of a concentrated solution of amino acids (by ion-exchange column chromatography on Dowex- 50X8), and b) determination of Phe and Tyr concentrations in the solution of amino acids by HPLC (using a Dionex Ultimate 3000 instrument equipped with a diode array detector). The analytical column was a Thermo Scientific Acclaim 120, C18, 5 μm Analitic (4.6 x 250 mm), coupled with an Acclaim C18 guard column. The values of Phe and Tyr concentrations in plasma of several patients were calculated using a calibration curve made with standards of Phe (1834.4 μmol/L in deionized water) and Tyr (600 μmol/L in deionized water). Concentrations as low as 24 μmol/dL of Phe and 15 μmol/dL of Tyr could be determined. Conclusion. The whole procedure presented here is relatively simple, rather inexpensive, however very sensitive and accurate. Consequently, it is very adequate for confirming the diagnosis of PKU in patients with neonatal hyperphenylalaninemia, as well as for monitoring the plasma concentrations of Phe and Tyr in patients with PKU.

Objective. To investigate the impact of body weight on the subclinical hypothyroidism observed in patients with PCOS. Methods. The study included 95 normal weight (Group-1) and 122 overweight or obese women (Group-2) with PCOS. The control group consisted of age and BMI matched healthy individuals and grouped as normal weight (n: 66, Group-3) and overweight or obese (n: 65, Group-4. Women with chronic disease such as overt thyroid dysfunction, late-onset adrenal hyperplasia, and diabetes were excluded from the study. Plasma glucose and lipid profile, thyroid hormones, insulin, FSH, LH, total testosterone, estradiol, progesterone and DHEA-S were measured. Results. While fasting glucose was similar, insulin and HOMA-IR were higher in Group-2 and Group-4 (p: 0.001). The groups were similar with respect to FSH, Estradiol, prolactine, DHEAS. While total testosterone and LH levels were higher (ptestosterone: 0,009), progesterone was lower in both PCOS groups (pprogesterone: 0.041). Free T3, free T4, thyroid antibodies were similar between the groups, but the prevalence of subclinical hypothyroidism was greater in Group-2 and -4 than in Group-1 and -3 (p: 0.044). TSH was only correlated with BMI (r: 0.122, p: 0.02). Conclusion. The increased prevalence of subclinical hypothyroidism in women with PCOS might be the result of increased BMI.

The aim of the study was to evaluate the prevalence of hyperhomocysteinemia in hypothyroid patients and the effect of folic acid supplementation when serum homocysteine\r\n(Hcy) was over risk level.\r\nPatients and methods. Patients with moderate (Group1) and severe hypothyroidism (Group 2) were evaluated before any therapy and after 6 months of combined folic acid and\r\nlevothyroxine substitution, versus control subjects. Hcy, folic acid, thyroid hormones and lipids were measured for all subjects. Thyroglobulin and antithyroglobulin antibodies were measured only for Group 2.\r\nResults. Only 17 % of the cases had basal Hcy at non risk level (<10 mmol/L). Both groups had higher Hcy levels than control (p <0.0001). In Group 1 basal folic acid was lower\r\nthan in control and group 2 (p<0.001). No correlation was found between high levels of Hcy (> 12 mmol/L ) and positive thyroglobulin. After 3 months of combined therapy, significant decrease of Hcy (p<0.0001) was observed compared with the basal level. Normalization of\r\nHcy appears during next 3 months even with reducing the folic acid supplementation.\r\nConclusion. Our results report moderate hyperhomocysteinemia in hypothyroid patients. This may exacerbate the cardiovascular risk traditionally attributed to lipid changes. Six months of combined therapy (L-thyroxine and folic acid) corrected hyperhomocysteinemia excluding the additional risk.

Background. An increasing number of studies suggest that hypothyroidism may lead to hepatorenal toxicity. This study examined whether thymoquinone (TQ), the main active Nigella sativa constituent, could prevent the detrimental influences of hepatorenal toxicity of hypothyroidism during the juvenile period in rats. Methods. The male rats were randomly divided into four groups (n = 7), including control, propylthiouracil (PTU), PTU-TQ 5 mg/kg, and PTU-TQ 10 mg/kg. PTU was dissolved in drinking water at a concentration of 0.05% and administered for six weeks. In the PTU-TQ5 and PTU-TQ10 groups, animals received PTU plus 5 mg/kg and 10 mg/kg of the TQ (i.p.) for six weeks, respectively. The rats were evaluated after TQ treatment by measuring serum markers of liver and kidney function tests as well as oxidative stress biomarkers in liver and kidney tissues. Results. Administration of TQ (5 and 10 mg/ kg) decreased oxidative stress damage in liver and kidney tissue in hypothyroidism rats with improvement in activities of antioxidant enzymes and a decrease in MDA in both liver and kidney homogenates. Furthermore, TQ treatment significantly inhibited the elevation of serum biochemical markers of liver and kidney function associated with this hepatorenal toxicity. Conclusion. These results suggest that the protective effect of TQ in hypothyroidism-induced hepatorenal toxicity in rats is attributed to its ability to reduce oxidative stress in hepatic and renal tissues. However, more studies are recommended to investigate the exact mechanism (s) for the effect of TQ on hepatorenal outcomes of hypothyroidism in human subjects.

Oxidative stress is defined as a rupture in the prooxidant-antioxidant balance in favor of\r\nthe former, leading to characteristic changes in biomolecules of all types, and to tissue damage.\r\nIt was implied in ageing-related processes, both by direct actions of various oxidative adducts\r\nand by its cardiovascular consequences. In the latest years, it has become evident that chronic\r\nkidney disease (CKD) is itself a condition characterized by oxidative stress. Although\r\nconflictual results were reported in non-dialysis CKD patients, there is an increasing trend in\r\noxidative stress markers and a decreasing one in antioxidative activity along with progressive\r\nreduction in glomerular filtration rate. A combination of inflammation, abnormal nutrition,\r\ndisturbed metabolism by the uremic milieu and defective renal clearance seems to be the cause.\r\nClearly, longitudinal studies with larger participation are necessary to define the precise\r\ncontribution of each element and the relationships between oxidative stress and CKD\r\nprogression. In dialysis CKD patients, bioincompatibility reactions during HD sessions\r\n(dialyzor membrane, dialysis solution), anemia and its therapy (iv iron) come into play. The\r\nclinical consequences of oxidative stress are difficult to ascertain, because oxidative stress,\r\ninflammation and malnutrition were found to be, in various proportion, strong predictors of\r\noutcome in CKD patients, but the precise contribution of each factor is difficult to elucidate for\r\nthe moment.