ACTA ENDOCRINOLOGICA (BUC)

Context. Tumors associated with thyroid gland are relatively rare. Papillary thyroid cancer (PTC) represents the most\r\nfrequent thyroid neoplasm, and it has almost in all of the cases favorable prognosis. In the largest number of the cases, PTC remains within the thyroid gland or it gives the\r\nlymphogenic metastasis in the cervical lymph nodes and, extremely rare, it results in hematogenic metastasis.\r\nObjective. To present a case of a patient who had a distant secondary deposit in pelvic bone and sacral bone as a first sign of the PTC.\r\nSubjects and Methods. A 56 year old male was presented in this report.\r\nResults. After intensive hip pain, patient was diagnosed with osteolytic lesion in sacral and left pelvic bone. After aspiration biopsy, macroscopic analysis and imunohistochemistry, diagnosis of PTC was set. Patient has undergone total thyroidectomy, two doses of radioiodine\r\nwere applied and secondary deposit palliative radiotherapy as well.\r\nConclusions. The total thyroidectomy is the first line therapy in the PTC patients for primary tumors, while the therapy for the secondary deposits requires surgical\r\nprocedures combined with other means of treatment.

Context. Vitamin D plays a crucial role in calcium metabolism through parathormone-dependent process. Deficiency of this important nutrient may be associated with hypocalcemia after thyroidectomy. Objective. To evaluate the role of vitamin D in predicting hypocalcemia following total thyroidectomy. Subjects and Methods. One hundred and fifty patients who underwent total thyroidectomy for benign or malignant thyroid disease were included in this prospective study. The association between preoperative vitamin D status and the development of hypocalcemia were investigated. Results. Biochemical and symptomatic hypocalcemia were found in 28 (18.7%) and 22 (14.7%) patients, respectively. Preoperative vit D level was found significantly lower in patients with biochemical (p = 0.006) and clinical (p < 0.001) hypocalcemia in comparison to normocalcemic patients. The patients who had <10 ng/mL vit D level (severe deficiency) developed significantly more biochemical and clinical hypocalcemia than the patients with serum vit D level higher than 10 ng/mL (p = 0.030 and p < 0.001, respectively). Conclusions. Although postthyroidectomy hypocalcemia is multifactorial, vit D deficiency, particularly severe form, is significantly associated with the development of biochemical and clinical hypocalcemia. Vit D supplementation can prevent this unwanted complication in such patients.

Background. Paget Disease (PD) is usually asymptomatic and discovered incidentally, it is known that it is exhibited low to high grade increased F-18 FDG uptake. Aim. In this study, we investigated the distinguishability of FDG PET/CT in incidental PD cases from other bone diseases and at different stages of the disease. Patients and Methods. In this cross-sectional, descriptive study, “Paget” identification associated with PET/ CT reports was found in 69 of 18,119 studies (~3.8%). Of the 45 patients (33 males and 12 females) eligible for inclusion in the study, 35.6% had monostotic and 64.4% had polyostotic disease (p>0.5). There was no statistically significant difference in biochemical parameters between groups. Results. According to the radiological appearance of the patients, 36 were in the mixed stage and 9 were in the blastic stage. Only the difference in ALP and creatinine values between the groups was statistically significant. SUVmax, SUVmean and HU values were found to be statistically significantly higher in pagetoid bones compared to control bone lesions. For SUVmax for PD bone lesion we found the 2.55 cutoff point with a sensitivity of 91% and a specificity of 84%. Conclusion. The specific radiological appearance of bone lesions and the evaluation of metabolic activity compared to normal bone seem to help differentiate PD from other lesions. Prospective studies are needed in the differentiation of FDG's disease stage and treatment response evaluation. The ability to differentiate between benign and malignant FDG avid bone lesions in oncological patients’ enables appropriate patient management, including avoiding unnecessary additional invasive procedures such as bone biopsy.

Context. Peripheral nerve lesions are a major complication of diabetes mellitus, the main clinical manifestations of which are numbness and pain involving the limbs. Objective. To determine the correlation between pregabalin treatment and diabetic peripheral neuropathic pain. Design. An experimental animal study in BALB/c mice. Subjects and Methods. Diabetes models are established by injecting streptozotocin (STZ) into the abdominal cavities of mice. The correlation between the treatment effect, time, and dosage of pregabalin was determined. The effect of a type 1 organic cation transporter (Octn1) in the absorption of pregabalin was evaluated. Results. Pregabalin reduced tactile allodynia in diabetic mice. The best analgesic effect occurred when intestinal absorption was increased. Octn1 mediated pregabalin entry into intestinal epithelial cells, which influenced the absorption of pregabalin with a timedependent fluctuation in the small intestine. Peripheral nerve damage caused by diabetes was dependent on time and dose of pregabalin, which was related to the regular expression of Octn1 in small intestinal epithelium. Conclusions. Peripheral nerve damage caused by diabetes was dependent on time and dosage of pregabalin, which was related to the regular expression of Octn1 in small intestinal epithelium.

Context. GLP-1 is a peptide hormone highly conserved among mammals that derives from a tissue specific post-translational processing of the proglucagon gene. It is known to be produced in the intestinal L-cells as a consequence of pro-hormone convertase PC 1/3 cleavage of major proglucagon fragment. It has a role as “incretin” stimulating postprandial insulin synthesis and secretion, somatostatin release and inhibiting glucagon secretion. Recently a role has been assigned in embryological processes and in the differentiation of the pancreatic β-cells. Objective. The aim of this study was to describe GLP-1 distribution in the canine embryo. Methods. Paraffin sections obtained from 6 thirtydays canine embryos collected from two different mothers during hysterectomy were used in the present study. Immunolocalization of GLP-1 and Chromogranin-A was performed by using the peroxidase method. Colocalization studies were also accomplished by immunofluorescence. Results. We detected GLP-1 only in the developing primordial of pancreas where it did colocalize sometimes with Chromogranin-A. Intestinal presence of GLP-1 was not detected. Chromogranin-A was very seldom observed in the developing duodenum. Conclusions. Our results suggest an embryologic role of GLP-1 in pancreas organogenesis. This speculation is further corroborated by the recent literature data on the potential role of the α-cells in stimulating either the generation (embryos) or the re-generation of β-cells together with the GLP-1 ability to modulate different pathways involved in tissue morphogenesis and differentiation.

Objectives: to determine the 24-hours profile and the clinical implications of hyperchloremic metabolic acidosis (HCMA) following cardiac surgery with cardiopulmonary bypass (CPB).\r\nSubjects and methods: prospective and observational study set in cardiac anesthesia and intensive unit. One hundred patients with cardiac procedures with CPB, mean age 56 years, mean body weight 71 kg, were enrolled. Sampling of arterial blood for gas, acid-base parameters (pH, carbon dioxide partial pressure, base excess, concentration of bicarbonate and anion gap) and serum electrolytes (sodium, potassium, chloride) were performed at four time points: 30 min after induction of anesthesia (T1), after completion of CPB (T2), at 6 hours (T3) and at 24 hours postoperatively (T4). The volume of fluids administered intraoperatively and 24 hours postoperatively as well as major complications: bleeding, arrhythmias and organ dysfunctions (renal, pulmonary or neurological) were also registered. For statistical analysis we used a t-test (p<0.05).\r\nResults: Seventy-three (73 %) of the patients developed metabolic acidosis during the observation period. Sixty-six (66 %) patients had HCMA. Mean chloride concentrations were at T1, T2, T3, and T4: 103 mmol/L, 113 mmol/L, 111 mmol/L and 108 mmol/L, respectively. The chloride concentration was significantly higher at T2 and T3 as compared to baseline. There were no statistical differences between patients with and without HCMA, neither in the amount and type of fluids administered perioperatively, nor in the incidence of bleeding, arrhythmias, and organ dysfunctions.\r\nConclusions: HCMA is common after cardiac surgery. It is a transient and benign acid-base disturbance. In our low risk cardiac surgery patients, HCMA was not associated with major postoperative complications.

Despite several attempts to establish the role of QUS in clinical practice, issues such as definition of osteoporosis based on QUS, screening strategy and therapy efficacy for patients identified by QUS as having high risk of fracture remain a matter of debate. The present study aimed to evaluate the diagnostic agreement between two QUS techniques (heel QUS and proximal phalanges QUS) and DXA in an unselected population of Romanian women aged 24- 80 years, as well as to offer cut-off levels for QUS to distinct between women with or without osteoporosis identified by DXA. In women measured by both DXA and calcaneus QUS (c- QUS), bone mineral density (BMD) moderately correlated with stiffness index (SI) (L1-L4: r=+0.51, p<0.001; femoral neck: r=+0.53, p<0.001; hip: r=+0.57, p<0.001), while in women examined by both DXA and phalanx QUS (ph-QUS), BMD was positively related to amplitude-dependent speed of sound (Ad-SoS) (L1-L4: r=+0.47, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001) and ultrasound bone profile index (UBPI) (L1-L4: r=+0.44, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001). At a T-score cutoff level of -2.5SD, the high specificity but low sensitivity suggests a low false positive rate of c-QUS as a diagnostic test; still, several patients with the disease may not be correctly diagnosed. At the same cut-off level, ph-QUS showed higher sensitivity and lower specificity. Diagnostic agreement between DXA and QUS was poor, with k-scores ranging from 0.33 to 0.39 for c-QUS and from 0.14 to 0.29 for ph-QUS, respectively. Lowering c-QUS T-score cutoff for lumbar spine osteoporosis screening to -1.5SD and ph-QUS T-score cut-off to -1.9SD, respectively, improved sensitivity and had a minor effect on diagnostic agreement. Regardless of the evaluated site, neither c-QUS nor ph-QUS does represent an adequate predictor of BMD in Romanian women. Changing the diagnostic T-score threshold from -2.5 SD to -1.5 SD and -1.9 SD in subjects examined by c-QUS or ph-QUS, respectively, is followed by improved sensitivity and diagnostic agreement in the identification of patients with vertebral osteoporosis. Cut-off values may allow QUS to be used as a screening tool for spine and femur osteoporosis.

Context. Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. The increasing evidence supports links between inflammation and AF. There is evidence showing that obesity is a major cause of adipose tissue (AT) inflammation. Ghrelin (GHRL), through its growth hormone secretagogue receptor (GHS-R) present on adipose tissue macrophages (ATMs), could modulate AT inflammation. Objective. Our study aimed to evaluate the role of adipose tissue macrophages (ATMs) and their GHS-R in adipose tissue samples of right atrial appendages (RAA) biopsies. Subjects and Method. We obtained RAA biopsies from 10 obese patients, undergoing cardiac surgery for coronary artery bypass graft (CABG) and developing postoperative atrial fibrillation (POAF). The epicardial tissue samples were examined using immunohistochemistry to visualize and quantify CD68 and GSH-R expression of the ATMs. Results. Histologically, the mean adipocyte diameter (MAD) of epicardial adipose tissue (EAT) was larger in EAT samples with inflammation as compared to EAT without inflammation (84.2 μm vs. 79.6 μm). The expression of CD68 was lower in EAT without inflammation as compared to EAT with inflammation in adipose tissue samples. Similarly, the expression of GSH-R was lower in EAT samples without inflammation as compared to EAT samples with inflammation in adipose tissue. Conclusions. Increased epicardial fat area, macrophage infiltration, and GHS-R expression in epicardial ATMs appeared to be associated with postoperative atrial fibrillation in obese patients.

Background. Prevalence of congenital hypothyroidism is about one per 414 live births in Kurdistan Province, a western province in Iran. Recently, a surveillance system (diagnosis, report and treatment) was developed to control the disease in Iran. Aim. This study aimed to compare the IQ of children with congenital hypothyroidism with normal children in this province, where the disease is highly prevalent. Subjects and Methods. This retrospective cohort study was conducted on 100 children with congenital hypothyroidism under continuous treatment with thyroxine and a group of 100 healthy infants. Two tests of Goodenough draw-a-man test and Proteus Mazes were used to measure IQ. Statistical analysis was done by SPSS 16 and multiple regression. Results. The average IQ of the patient group treated for 42 months with thyroxine and healthy group were 103.4 (±16.9) and 103.4 (±15.4), respectively (p=0.989). There was no statistically significant difference between the IQ of children with transient and permanent hypothyroidism. In multivariate analysis, the only effective factor on IQ was mothers’ education. Conclusion. There was no statistically significant difference between the IQ of children with congenital hypothyroidism who have been treated with thyroxine and the IQ of healthy children. So, there is appropriate quality of care for patients who are living in this province where the disease is highly prevalent.

Objective. Ectopic posterior pituitary gland (EPP) is usually characterized by an abnormal pituitary stalk and hypoplasia of the anterior hypophysis. The genetic mechanisms involved in the development of EPP remain uncertain. The aim of this study is to determine whether mutations in the three genes, PROP-1, LHX2, and POU1F1, are associated with the risk for and the characteristics of EPP. Methods. In the Endocrinology Outpatient Clinic of “Dr. Behcet Uz” Children’s Hospital, 27 patients with EPP were submitted to sequencing analyses of the PROP-1, LHX2, and POU1F1 genes. Results. Growth hormone, thyrotropin, corticotropin, gonadotropin, and vasopressin deficiency were observed in 22 (81.5%), 23 (85.2%), 17 (63%), 14 (51.9%), and two (7.4%) patients. Thirteen patients (48.1%) presented with hyperprolactinemia. Fourteen patients (51%) had a history of birth dystocia, and 12 cases (42.1%) had a history of breech presentation. Central nervous system abnormalities included five cases with corpus callosum agenesis, one case with schizencephaly, and one case with Chiari type 1 malformation. We identified a homozygous p.S109* mutation in exon 2 in one male patient with EPP and two different PROP1 gene polymorphisms (A142T or c.109+3 G>A polymorphism) in thirteen patients. Conclusions. Our results suggest that PROP1 gene abnormalities might explain the genetic mechanisms involved in the development of EPP.