ACTA ENDOCRINOLOGICA (BUC)

Introduction. The blood brain barrier (BBB) restricts the transport of hydrophilic molecules such as peptidic pituitary hormones into the brain tissue. The blood-cerebrospinal fluid (CSF) is a part of the BBB.\r\nAim To compare the pituitary hormone levels on the two sides of the BBB in a group of subjects without endocrine diseases.\r\nPatients and methods. We investigated, with the approval of the local ethics committee, 78 subjects without endocrine diseases. Growth hormone (GH), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and thyroid stimulating hormone (TSH) were measured by rapid fluoroimmunoassay with Europium in the blood and cerebrospinal fluid (CSF)sampled simultaneously before rachianestesia for minor surgery.\r\nResults. CSF concentrations are significantly lower than the corresponding serum ones for all hormones studied: 0.04 ? 0.009 mU/mL vs 2.29 ? 0.57 mU/mL for GH, 1.49 ? 0.078 ng/mL vs 10.07 ? 1.42 ng/mL for PRL, 0.57 ? 0.078 U/L vs 22.71 ? 3.65 U/L for FSH, 0.39 ? 0.038 U/L vs 11.11 ? 1.55 U/L for LH and 0.01 ? 0.003 &#956;U/mL vs 1.36 ? 0.17&#956;U/mL for TSH (mean ? SEM; p<0.001). The CSF/serum ratio was below 1 in the vast majority of cases (from all subjects studied we only found 3 cases with supraunitary CSF/serum ratio). The serum and CSF levels were not significantly correlated for\r\nany of the pituitary hormones. Comparing preand postmenopausal women the CSF gonadotropin levels were slightly but nonsignificantly increased after menopause,\r\ndespite marked differences in the serum concentrations: CSF FSH 1.21 ?0.17U/L after vs 0.84? 0.4U/L before menopause, CSF LH 0.60? 0.047U/L after vs 0.43? 0.14U/L before\r\nmenopause. The CSF/ serum ratio for FSH markedly decreased after menopause (0.02?0.003 vs 0.22?0.11) although the effect did not reach statistical significance. The same\r\nwas true for CSF/serum LH ratio (0.026?0.005 vs 0.09?0.002). For none of the hormones studied the CSF levels correlated with age.\r\nConclusion. Pituitary hormones are normally found in the CSF at much lower levels than in the serum. The CSF hormonal\r\nconcentrations do not significantly correlate with the serum ones.

Introduction. Even if the last decade brings new information about the existence of the local pulmonary renin-angiotensin system (RAS), published results about its involvement in the progression of various pulmonary diseases remain contradictory. Methods. Using an experimental model of pulmonary allergic disease induced by ovalbumin (OVA) sensitization we studied effects of intratracheal (i.t.) administrated AT1 receptor blocker losartan (LOS) on inflammatory processes supposed to be mediated by pulmonary RAS. Alterations in bronchoalveolar lavage fluid (BALF) cellularity and variations of airway reactivity from OVA sensitized and challenged rats after LOS or vehicle i.t. instillation were comparatively assessed. Results. Blocking of RAS decreased the total BALF cellularity and polymorphonuclear cell count. LOS instillation also reduced the increases in specific airway resistance (sRaw) induced by inhalation of allergen (with 20%) or acetylcholine (with at least 15%). Conclusions. Our data suggest that expressly blocking of local RAS by i.t. administration of LOS have inhibitory effects on allergen - induced lung inflammation and sustain the participation of pulmonary RAS, activated by local or systemic factors, in lung diseases.

Context. Endometriosis is a common gynecological disease, characterized by ectopic deposits of endometrial tissue outside of the uterine cavity, and it is associated with pelvic pain and infertility, with an important impact on the quality of life. At this point there is a controversy regarding the etiology and pathophysiology of endometriosis and it seems that pro-angiogenic growth factors might be involved, but their role is not completely understood. Objective. To evaluate the serum concentration of the main growth factors in patients with diagnosed endometriosis compared to healthy controls. S ubjects and Methods. A total of 157 women were divided into two study groups (Group I – endometriosis; Group 2 – healthy women). Serum levels of VEGF, G-CSF, GM-CSF, b-FGF, EGF, and HGF were measured with Human Multiplex Cytokine Panels. Results. VEGF serum levels were significantly lower in women with endometriosis compared to controls (1.924±0.145 compared to 1.806±0.078 pg/mL, p<0.001). Serum levels of GM-CSF, b-FGF, EGF, and HGF respectively did not differ significantly between patients with endometriosis and healthy controls. G-CSF had a very low detection rate. Conclusions. The present study showed that VEGF serum levels are significantly lower in endometriosis patients compared to healthy controls, indicating a possible role in endometriosis pathogenesis.

Context. Thyroid disorders are common in diabetics and related to severe diabetic complications. TRPV2 ion channels have crucial functions in insulin secretion and glucose metabolism which have an important role in the pathophysiology of diabetes. Also, they have a significant effect on various immunological events that are involved in the HT pathophysiology. Objective. This study aimed to investigate rs14039 and rs4792742 polymorphisms of the TRPV2 ion channels in type 2 diabetes mellitus (T2DM, n=100) Hashimoto thyroiditis (HT, n=70) and comorbid T2DM and HT (T2DM+HT, n=100) patients and control (n=100). Design. Case-control study Subject and Methods. RT-PCR genotyping was used to determine rs14039 and rs4792742 polymorphisms with DNA samples of subjects and appropriate primer and probes. Besides, required biochemical analyses were performed. Results. It was determined that the frequencies of the rs14039 GG homozygote polymorphic genotype and the G allele were significantly higher in T2DM+HT patients compared to the control (p=0.03 and p=0.01, respectively) and that especially the GG genotype increases the risk of T2DM+HT 3.046-fold (p=0.01, OR=3.046). It was detected that the GG genotype increased the risk of HT 2.54-fold (p=0.05, OR=2.541). TRPV2 rs4792742 polymorphisms reduce the risk of HT and T2DM+HT comorbidity almost by half and have a protective effect against HT and T2DM+HT. Conclusion. The rs14039 GG genotype of the TRPV2 gene significantly increases the risks of development of T2DM+HT and HT disorders, may have a significant role in the pathophysiology of these diseases, also leading to predisposition for their development. Conversely, rs4792742 polymorphic genotypes have a strong protective effect against the HT and T2DM+HT comorbidity.

Context. There is no consensus regarding routine usage and benefits of molecular markers for prediction of prognosis and assessment of risk groups in differentiated thyroid cancer (DTC). Objective. We aimed to investigate NIS, Galectin-3, PTEN, P53 and Ki67 expressions in tumor tissue and metastatic lymph nodes in PTC and their association with lymph node metastasis and prognosis. Material and Methods. Ninety two papillary thyroid cancer patients who underwent total thyroidectomy and central lymph node dissection were included in this study. NIS, Galectin-3, PTEN, P53 and Ki67 immunohistochemical stainings were performed for all surgical tumor tissues and metastatic lymph nodes of the 38 patients. Age, gender, tumor size, multifocality, capsular invasion, extrathyroidal extension and lymphocytic thyroiditis were assessed retrospectively. Results. Seventy three females (79.3%) and nineteen males (20.7%) were included in this study. Risk of lymph node metastasis was higher in tumors with capsular invasion and extrathyroidal extension (p=0.03 and p < 0.001). NIS, PTEN and Galectin-3 protein expressions in tumor tissue were not associated with gender, tumor size, multifocality, extrathyroidal extension, capsular invasion, lymph node metastasis and tumor recurrence. Mean Ki 67 proliferation index was 2.08±0.95%. Ki 67 proliferation index was associated with tumor size (p=0.012). Intensity and expression of NIS and PTEN in tumor tissue were concordant with intensity and expression in metastatic lymph nodes (p<0.001). Ki 67 proliferation index in tumor was concordant with metastatic lymph nodes (p=0.02). Conclusions. NIS, PTEN, Galectin-3, Ki67 and P53 expressions were not associated with the risk of lymph node metastasis in PTC patients. Routine analysis of these markers does not seem to be favorable. Further studies with new markers are necessary to determine prognostic predictors.

Background. Although thyroid nodules are a common finding in the general population, determining the clinically important nodules is essential. We investigated thyroid nodules or cysts by thyroid ultrasonography (US) in patients with β-thalassemia major (β-TM) and intermedia (β- TI). We also report a β-TI patient who was diagnosed with thyroid cancer six months before our screening. Methods. In this cross-sectional study, 178 patients with β-thalassemias referred to the Thalassemia Clinic in a tertiary hospital affiliated to Shiraz University of Medical Sciences were investigated, from January to June 2016, by US. Results. Thyroid nodules or cysts were detected in 11 patients [total: 6.17 %; 8 patients with β-TM (8.2%) and 3 patients with β-TI (3.7%)]. All nodules were < 1 cm in diameter and were not suspicious of malignancy. All patients, after 1 year of thyroid US follow-up, did not show any significant change in favor of malignancy. Conclusion. Based on our results, the frequency of thyroid nodules was similar to what was reported in the general population. However, a long-term follow-up of these patients is recommended because of the potential carcinogenic effects of iron and hepatitis C infection (HCV). To achieve more precise information, collaborative multicenter studies should be considered.

Background. Previous sleep studies suggest that type 2 diabetes mellitus is associated with poor quality of sleep and sleep disorders. Aim. To evaluate sleep parameters and diurnal preference in type 2 diabetic patients, using a questionnaire. Methods. Ninety seven patients (aged 55.8±8.3, sex ratio 1:1), previously diagnosed with type 2 diabetes mellitus, together with 102 controls (aged 47.1±10.5, sex ratio 1:1), without diabetes, completed a questionnaire containing the Romanian translation of the Composite Scale of Morningness, the Sleep Disorders Questionnaire, the Pittsburgh Sleep Quality Index, the Pittsburgh Insomnia Rating Scale, the Multidimensional Fatigue Inventory, the Epworth Sleepiness Scale, the Alcohol Use Disorders Identification Test and the Beck Depression Inventory II (BDI). The study was cross-sectional, as we included subjects from outpatient and inpatient facilities. The recruitment process was based on handing invitation letters to patients consulting their physician, as well as to their acquaintances, using the snowball sampling. Participation was voluntary and anonymous. Results. Insomnia was more often reported in diabetic patients: 32 (33.0%) vs. 16 (15.7%) controls, a difference that was highly significant (P<0.001). Diabetic patients used to wake up at approximately the same hour as controls did; nevertheless they went to bed earlier (22:14 ± 0:57 vs. 22:32 ± 1:03), needed more minutes to fall asleep (28.84 ± 21.01 vs. 24.32 ± 23.45) and slept less than controls (7.01 ± 1.56 vs. 7.23 ± 1.18). Statistically significant differences between patients and controls were found regarding the Pittsburgh Sleep Quality Index (P=0.005), the Pittsburgh Insomnia Rating Scale (P<0.001) and the Multidimensional Fatigue Inventory (P=0.001) scores. Eighteen (18.5%) patients also met the criteria for a depressive disorder. No significant differences between patients and controls were found as related to their chronotype (P=0.32) Conclusion. Poor sleep, but not diurnal preference, was linked with the presence of type 2 diabetes mellitus.

A 74 year old lady presented with difficulty in breathing and hypoxia. She was initially treated as pulmonary embolism\r\n(PE). However, confirmatory tests did not suggest the diagnosis of PE. Further tests gave the diagnosis of an ovarian carcinoid presenting with shortness of breath and\r\nhypoxia. After an initial treatment with Octreotide, she underwent salpingooophorectomy. She became asymptomatic and made an uneventful recovery. Ovarian carcinoids can\r\nproduce carcinoid syndrome without the presence of hepatic metastases. Here we provide a short review on ovarian carcinoids.

Paget’s disease is a disorder of aging bone which occurs in the setting of accelarated bone remodelling. In the presented case we discuss the difficulties in the diagnosis of Paget’s disease in a 77 year old patient with coexisting endometrium carcinoma. The patient was initially diagnosed with metastatic bone disease due to endometrium adenocarcinoma when she was admitted to oncology clinic with pelvic pain. Bone scintigraphy with Tc99 and (18) F fluorodeoxyglucose positron emission tomography/CT revealed an increased uptake on the bone lesions which were reported as metastatic bone involvement. Although the (18) F-FDG uptake was much higher than the levels that would generally be anticipated in a case with Paget’s disease, high levels of bone turnover markers indicated further evaluation in the differential diagnosis and the definitive diagnosis of Paget’s disease was established with the pathological evaluation of bone biopsy.

Introduction. Congenital adrenal hyperplasia (CAH) autosomal recessive disorders characterized by impaired adrenal steroid hormone synthesis. The most common form is 21-hydroxylase deficiency (21OHD). Testicular adrenal rest tumors (TARTs) are benign intratesticular masses that occur in male patients with CAH. TARTs are quite common in patients with 21OHD who were diagnosed late. Case report. A 41-year-old male patient with CAH secondary to 21OHD. The patient was referred to our endocrinology department from the andrology clinic for bilateral adrenal masses. Bilateral orchiectomy had been performed due to bilateral testicular masses and azoospermia two years ago. The pathology was reported as Leydig cell tumor. In hormonal assessment, baseline cortisol levels were low, 17-hydroxyprogesterone levels with baseline and after cosyntropin stimulation test were high. As a result of clinic and laboratory assessment, the patient was diagnosed with simple virilising CAH due to 21OHD and adrenal insufficiency. Then, prednisolone replacement was initiated. Bilateral orchiectomy tissue blocks of the patient were reassessed and were considered TART. Magnetic resonance imaging revealed bilateral adrenal masses with 88x55 mm on the right and 41x22 mm on the left. Laparoscopic right adrenalectomy was applied and pathology was reported as myelolipoma. Follow-up of the mass on the left adrenal gland is ongoing. The patient is monitored under prednisolone and testosterone replacement therapy. Early diagnosis of CAH is very important because of the complications it causes. It should be considered especially for bilateral testicular and/ or adrenal masses. Both fertility and adrenal glands can be protected with an early diagnosis and an early glucocorticoid replacement.