ACTA ENDOCRINOLOGICA (BUC)

Background. There are scarce data about prevalence of mineral metabolism (MM) disorders in Romanian predialysis patients, so we assessed their occurrence and relationships in mild to severe chronic kidney disease (CKD). Methods. One hundred fifteen non-dialysis CKD (eGFR 31, 95% CI 29-35mL/min) and 33 matched non-CKD subjects entered this multicentric, cross-sectional study. Serum 25-hydroxyvitamin D (25OHD), intact parathyroid hormone (iPTH), phosphate (PO4), total calcium (tCa) and alkaline phosphatase (AP) were measured, along with demographic and past medical history data. Results. Hypovitaminosis D was equally prevalent in Controls and CKD (91% vs. 96% had 25OHD<30ng/mL). Increasing proportions of hyperparathyroidism (33% - stage 2 to 100% - stage 5; p<0.001) and hyperphosphatemia (2% - stage 3 to 38% - stage 5; p<0.001) were found. Hypocalcemia was more prevalent in stage 5 (25% vs. 6% in stage 4, none in stage 3 and Controls, p<0.001). Mineral metabolism parameters correlated with eGFR. In addition, iPTH was directly associated with PO4, AP, and urinary albumin-tocreatinine ratio (ACR), but inversely with tCa and 25OHD, while negative correlation of 25OHD with age, AP, ACR, and C-reactive protein emerged. In multiple regression, eGFR was the only predictor of iPTH (Beta -0.68, 95%CI -1.35 to -0.90, R2 0.46, p<0.001), whereas age and ACR were the determinants of 25OHD (a model which explained 14% of its variation). Conclusions. Hypovitaminosis D was very common irrespective of CKD presence and severity, and it seems worsened by older age and higher albuminuria. Hyperparathyroidism preceded hyperphosphatemia and hypocalcemia, and it seems mostly dependent on kidney function decline

Background. Cerebral vein and sinus thrombosis (CVT) is less encountered, compared to arterial stroke. Commonly witnessed symptoms are headache, nausea, vomiting, confusion, aphasia, seizures, cranial nerve dysfunction and motor or sensorial deficits. The diagnosis is accurately determined by the help of MRI and MR venography. Multiple risk factors associated with CVT are present. Venous thrombosis tends to occur when there is an imbalance between prothrombotic and thrombolytic processes.\r\nCase report. In this report, a patient with CVT extending from left transverse and sigmoid sinuses to jugular vein and diagnosed with diabetes mellitus (DM) during this period\r\nwas discussed in light of literature. The 55-year-old man was evaluated in the neurology clinic with the complaints of headache, nausea, vomiting and blurred speech. On neurologic examination, he was diagnosed with sensorial aphasia and consequently, with DM over the hospital stay. On the cranial MR venography, CVT thrombosis was detected, extending from transverse and sigmoid sinuses to internal jugular vein. Decreased level of protein C and shortage of aPTT were\r\nfound. Anticoagulant treatment was carried out. All complaints were improved.\r\nConclusion. In our subject, the existence of decreased protein C and shortage of APTT, along with DM, is a situation to increase hypercoagulability and the risk of cerebral vein and sinus thrombosis.

Glycemic control can be impaired in active acromegaly and insulin sensitivity (IS) decreases with rising growth hormone (GH) levels.\r\nAim. To assess the short-term impact of transsphenoidal surgery for acromegaly on glycemic control. Methods. 11 patients with native active acromegaly due to pituitary macroadenoma were assessed before and after (2-3 months) transsphenoidal hypophysectomy. Serum glucose, GH and insulin levels were measured by immunoradiometric assay at 0, 30, 60 and 120 minutes during a 75 g OGTT before and after surgery. IGF-1 levels were measured by ELISA. Basal hepatic IS was assessed using HOMA-S% and QUICKI indexes and stimulated IS using OGTTISI. Basal and stimulated insulin secretion was assessed using HOMA-B% index and IGI respectively. Results. All patients had their acromegaly improved (mean?SD pretreatment nadir GH 34?24.7 ng/mL vs. 4.6?3.5 ng/mL postsurgery; p<0.001) but only one was cured (nadir GH<1 ng/mL, normal IGF- 1 level). Mean fasting serum glucose was lowered by 7.9 mg/dL (95% CI 1.3-14.4, p=0.03) and fasting serum insulin by 9.6 mU/mL (95% CI 1.0-18.1, p=0.02). IS increased after surgery as shown by HOMA-S% index which rose 0.25?0.18 to 0.5?0.36 (p<0.01), QUICKI which rose form 0.31?0.03 to 0.33?0.03 (p=0.001) and OGTTISI index which rose from 2.5?1.6 to 5.1 ? 3.5 (p=0.002). Insulin secretion was unchanged as shown by HOMA-B% index (313?229 presurgery vs. 227?139 postsurgery, p=NS) and IGI index (0.96 ? 0.86 presurgery vs. 0.55 ? 0.49, p=NS). Conclusions. Partial removal of the pituitary adenoma by transsphenoidal surgery in patients with acromegaly induces a significant increase in insulin sensitivity and an improvement in glycemic control at 3 months after surgery. This suggests that transsphenoidal surgery should be indicated even if complete removal of the pituitary adenoma is not achieved.

Background. Hashimoto thyroiditis (HT) is an autoimmune disease and the most common cause of hypothyroidism. The widespread lymphocyte infiltration in the thyroid gland and intolerance of the body against its thyroid antigens leads to the destruction of thyroid cells and impaired thyroid function. Granulysin (GNLY) is a cytolytic antimicrobial peptide that has been associated with a wide range of diseases such as various infections, cancer, transplantation, and skin problems. However, there are a few studies investigating the relationship between HT and granulysin. Aim. Our study aims to investigate whether granulysin levels and GNLY gene polymorphism contribute to the damaged immune response leading to HT. Material and Methods. 100 unrelated patients diagnosed with HT and 140 healthy individuals were included in our study. Frequencies of GNLY rs10180391 and rs7908 gene polymorphisms were determined using PCR- RFLP method and serum granulysin levels were determined using ELISA. Results. There is no statistical significance between patient and control groups in terms of genotype and allele frequencies of GNLY gene polymorphisms and serum levels of granulysin. Conclusion. In conclusion, granulysin and GNLY gene polymorphisms do not appear to relate to HT disease.

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.