ACTA ENDOCRINOLOGICA (BUC)

Objective. To evaluate circulating FFAs in relation to glucose and insulin metabolism and to different fat compartments in men with and without diabetes. Patients and Methods. Thirtythree men with uncomplicated type 2 diabetes mellitus (T2DM) and 28 controls underwent an oral fat load and were studied at baseline and for 5 hours postprandially for serum FFAs, glucose and insulin. Abdominal fat distribution and gluteal fat accumulation were evaluated by anthropometrics and axial MRI images. Insulin resistance and sensitivity were estimated by HOMA and Matsuda index respectively. Results. Fasting and postprandial FFAs were higher in diabetics (p=0.007) despite similar fat accumulation and distribution between groups. Postprandial FFAs correlated positively with postprandial glucose, and fasting and postprandial insulin levels (p< 0.05) in controls, and with fasting and postprandial insulin levels (p< 0.05 and p < 0.01 respectively) in diabetics. Postprandial FFAs were positively correlated to HOMA (p<0.01) and negatively to Matsuda index (p<0.05), and positively to total visceral and retroperitoneal fat,the strongest association observed at L2- L3 (p<0.05 and p<0.001 respectively) in diabetics. Conclusions. Diabetics have higher serum FFAs, despite similar levels of adiposity and fat distribution. Interestingly, postprandial FFAs correlate strongly and positively with total visceral fat, underlying the importance of visceral fat in metabolic abnormalities in diabetes.

Objective. To compare two chromatographic methodologies for determination of plasma phenylalanine (Phe) and their usefulness for diagnosing hyperphenylalaninemia (HPA) and phenylketonuria (PKU). Methods. The plasma amino acids were isolated and concentrated from blood collected from infants with HPA detected by newborn screening. The plasma Phe was determined in parallel by HPLC and by image-densitometry of 2D-TLC plates. Results. Typical examples of 2D-TLC plates and HPLC chromatograms from infants with HPA and PKU are presented and evaluated. The Phe spot was visible on 2D - TLC plates at Phe concentrations higher than 300 μmol/L. The standard calibration curve traced after imagedensitometry of the Phe spot presented high dispersion of values at each concentration of Phe, high SD values, the equation of the curve having a low R-squared value (0.862). In contrast, the standard calibration curve obtained by HPLC shows linearity on the range of concentrations from 100 - 16,000 μmol/L, extremely small SD values, the equation of the curve has a very high R-squared value (0.999). Conclusions. The HPLC methodology is appropriate to confirm HPA detected by newborn or selective screening of PKU. The 2D - TLC methodology is adequate to detect patients with severe PKU.

Background. Gestational diabetes mellitus (GDM) is associated with high frequency of obstetric complications, such as gestosis, polyhydramnios, urogenital infection, premature birth. An increase in the number of cases of detection of GDM in pregnant women living in Kazakhstan is noted recently. Objective. This research was carried out in order to see the influence of GDM on the course of the third trimester of pregnancy, outcomes and fetal status in women of Kazakh ethnic group. Research design. Cohort observational study. Subjects and Methods. The main group of research consisted of 61 pregnant women with GDM (Meanage= 32.8±6.314), the control group included 39 pregnant women with normal glucose tolerance (Meanage=30±5.432 years). The pregnant women in both groups were examined by calculation of body mass index (BMI), determination of fasting plasma glucose and the system of hemostasis. Also, the fetal ultrasound was implemented and the uterineplacental, fetal-placental blood flow were evaluated using the Doppler mode. Results. In the main group initial BMI was equal to Mean=31.1±7.433 kg/m2; we revealed manifestation of gestational hypertension in 36.1%, 95%CI (2.52, 48.6); preeclampsia was diagnosed in 14.8% (95%CI (8; 25.7); the disorders of uteroplacental and fetoplacental blood flow recorded significantly more frequently in main group RR=6.393, 95%CI (1.581-25.840), like the diabetic fetopathy RR=5.115, 95%CI (1.240-21.033). The premature delivery, the prevalence of induction of delivery and intranatal trauma were significantly more frequent in women with GDM. Conclusions. GDM significantly worsens course of gestation.

The coexistence of Cushing’s syndrome (CS) and pregnancy is uncommon due to the suppression of gonadotropin secretion in CS. Adrenocorticotropic hormone (ACTH) dependent CS in pregnancy is less frequent than adrenal causes. The diagnosis of CS during pregnancy is difficult since physiological changes in the hypothalamopituitary- adrenal axis may cause dynamic tests to be misinterpreted. Radiological imaging is limited. We report the case of a 27-year old woman with Cushing’s disease (CD) diagnosed in the 5th-week of pregnancy. The mild symptoms of hypercortisolism did not lead to serious complications for the mother or the fetus, so insulin was the only treatment used. The pregnancy was completed without any complications, and at 38 weeks of gestation a healthy female infant was delivered vaginally. Complications, such as hypocortisolemia and hypoglycemia, were not observed in the infant. Postpartum tests were consistent with CD. Contrast-enhanced pituitary magnetic resonance imaging revealed a microadenoma which was removed with transsphenoidal surgery. Histopathology revealed a pituitary adenoma with positive immunohistochemical staining for ACTH. Biochemical remission required prednisolone treatment, but the insulin requirement decreased significantly over time. As a conclusion, CD with mild features can be well tolerated during pregnancy, but the mother and the fetus must be monitored closely.

Background Supplementation of Lcarnitine is associated with improvement in some abnormalities present in hemodialysis (HD) patients. Objective. The study aim was to analyze the effect of oral L-carnitine supplementation on endothelial dysfunction (ED), oxidative stress (OS), inflammation and anemia in HD patients. Design. A prospective, longitudinal and observational study was performed in a single dialysis unit. Subjects and methods.We studied 31 HD patients: 21 patients formed the Lcarnitine supplementation group (group 1) and 10 entered the control group (group 2). At baseline and after 3 months of L-carnitine supplementation (500mg/day) we determined endothelial-dependent flow-mediated vasodilatation (FMD) and nitroglycerin induced endothelium independent vasodilatation, involving ultrasonographic brachial artery measurements, serum visfatin, malondialdehyde, body mass index, systolic blood pressure, diastolic blood pressure, interdialytic body weight gain, C-reactive protein, albumin, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, ferritin, transferrin saturation, hemoglobin, erythropoietin dose, calcium (Ca), phosphorus (P), parathormone and Kt/V . Results. In group 1, FMD (8.9 (4.5-12.5) to 10.6 (6.7-18), p=0.04) and Ca (8.4±0.6 to 8.8±0.5 mg/dL, p<0.001) significantly increased after L-carnitine supplementation, while visfatin (1.0 (0.2-1.3) to 0.4 (0-0.9) pg/mL, p=0.03), malondialdehyde (2.8 (2.4- 3.2) to 1.3 (1.2-1.5) nmol/mL, p<0.001) and P (5.6±1.3 to 5.0±1.2 mg/dL, p=0.005) significantly decreased. Albumin increased significantly in both groups (3.9±0.3 to 4.2±0.3 mg/dL, p<0.001 in group 1 and 3.7±0.3 to 4.0±0.3 mg/dL, p=0.02 in group 2). There were no other significant variations of the studied parameters. Conclusions. L-carnitine supplementation reduces ED, visfatin levels and markers of OS, but has no effect on inflammation, nutrition and anemia in HD patients.

Introduction. Primary osteoporosis during childhood and adolescence represents an uncommon condition, and secondary forms are more likely to manifest at this age due to chronic disease and adverse effects of medical treatment. Case report. The authors report the case of a young male patient with a history of multiple idiopathic nonvertebral fragility fractures in addition to a family history of maternal osteoporosis and fracture, in whom osteoporosis was confirmed according to 2013 International Society for Clinical Densitometry (ISCD) criteria. Bone markers indicated low bone formation marker osteocalcin. Genetic testing revealed homozygosity for Sp1 COL1A1 gene polymorphism in combination to Fok-I vitamin D receptor (VDR) heterozygous polymorphism, to contribute to low bone mass and increased fracture risk. Severe premenopausal osteoporosis was present in the patient’s mother, who was also tested positive for both gene polymorphisms. Conclusion. This case report highlights the association between COL1A1 and VDR candidate gene polymorphisms and fragility fractures in a family. Individual genetic testing might be of clinical value in idiopathic osteoporosis in young patients, identifying subjects at increased fracture risk.

Atherosclerotic Cardiovascular Diseases are the leading cause of death worldwide. Aim. To estimate the prevalence of cardiovascular risk (CVR) categories in the adult population (aged 40-79 years) of Romania. Design. The present study was part of the epidemiological, cross-sectional PREDATORR study (PREvalence of DiAbeTes mellitus, prediabetes, overweight, Obesity, dyslipidemia, hyperuricemia and chronic kidney disease in Romania). Subjects and Methods. Exclusion criteria: age <40/ or>79 years old and diagnosis of ischemic vascular disease. The CVR was evaluated using charts developed by the World Health Organization/ International Society of Hypertension (WHO/ISH) available for Europe B (epidemiological subregion where Romania was included). The CVR was divided into 5 categories: <10%, 10-20%, 20-30%, 30-40%, > 40%. Results. A total of 1631 subjects (57.0±10.7 years, 45.1% males) were included in the present study. The age and sex-adjusted prevalence of CVR >40% was 2.9% (95%CI 2.8-3.1%), CVR 30-40% was 1.85% (95%CI 1.8-1.9%), CVR 20-30% was 5.8% (95%CI 5.6- 6.0%) and 13.0% (95%CI 12.8-13.3%) of the adult Romanian population has a 10-20% CVR, these CVR categories being more frequent in male and older age. Diabetes, overweight/ obesity and smoking were associated with high CVR categories. Conclusion. Romania is one of the countries with high CVR, requiring CVD prevention measures.

Background. Primary lymph nodes gastrinomas are rare and difficult to diagnose not only because of their small size, but also because modern imaging techniques have limitations in detecting duodenal and/or adjacent lymph nodes gastrinomas. Endoscopic ultrasonography is particularly useful in the identification of gastrinomas and can provide cytopathological evaluation for a gold standard diagnosis. Aim. To report a rare case of periduodenal lymph node gastrinoma and to emphasise the value of endoscopic ultrasound evaluation in patients with Zollinger Ellison syndrome. Methods. Presentation of clinical case and comments. Results. The current study reports a rare case of a patient with a small size gastrinoma located extrapancreatically and extraduodenal in a periduodenal lymph node, which exhibited the Zollinger-Ellison syndrome. Gastroduodenoscopy evidenced moderate esophagitis and multiple, superficial gastroduodenal ulcers. Basal gastrin levels were elevated. Enhanced abdominal computer tomography showed a small tumor located near the pancreas head with a very fast and fine enhancement in an early arterial phase. Endoscopic ultrasound-guided fineneedle aspiration of the periduodenal lesion was performed. Histopathology and immunohistochemistry evaluation were positive for a low risk neuroendocrine tumor. A double dose of proton pump inhibitors was recommended resulting in an improvement of symptoms. No symptoms, endoscopic lesions or additional tumors at up to 9 months of follow-up were detected. Conclusions. We report a rare case of low risk lymph node gastrinoma, small in size at diagnosis with favorable results after a double dose of proton pump inhibitors was recommended. Using endoscopic ultrasound, an early and complete diagnosis was established.

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.

hormone (ACTH) mediated multisystemic state of adrenal hypercortisolism. An ACTH secreting benign pituitary tumor (adenoma) is the most common cause in the majority of patients with CD. Case report. This article describes a case of a 56-year-old woman presenting with clinical manifestations of hypercortisolism, with high plasma cortisol and ACTH levels that was suppressed with high-dose dexamethasone administration, suggestive of CD. Pituitary magnetic resonance imaging (MRI) of the sellar region was inconclusive. During the single photon emission computed tomography (SPECT) examination, an increased accumulation of technetium - 99m - hexakis - 2 - methoxy - isobutyl-isonitrile (99mTc-MIBI) in the pituitary gland area was noticed. Finally, response to corticotropinreleasing hormone (CRH) and ghrelin stimulatory testing, differentiated CD from ectopic ACTH and primary adrenocortical hypersecretion. Conclusion. We highlight the potential of 99mTc- MIBI SPECT as sensitive and specific method of pituitary gland adenoma detection in patients with Cushing’s disease, when MRI fails to directly detect an adenoma and stimulatory tests with CRH and ghrelin are not in routine diagnostics.