ACTA ENDOCRINOLOGICA (BUC)

Triple A syndrome is an autosomal recessive inherited multisystem disorder that was first described in 1978. Triple A syndrome has a high genotypic and phenotypic heterogeneity and has been linked with mutations in the AAAS gene, which has been identified on chromosome 12q13. A 14 years old male patient applied to outpatient clinic complaining of weakness and darkening of skin color since 4 months. On physical examination hyperpigmentation was observed on both the skin and mucosa. The morning cortisol level was 1.8 μg/dL and ACTH was >1250 ng/L. Schirmer test showed absence of tears. In the patient’s esophagoscopy, mucosal paleness and stenosis of the cardia were observed. Molecular genetic analysis of AAAS gene confirmed the diagnosis of triple A syndrome caused by homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38). This variant is considered to be a possible pathogenic because it causes a frame shift that changes the protein structure. As a result of the genetic analysis of the patient’s parents, the AAAS gene was detected as heterozygous in both parents for the c.1368_1372delGCTCA mutation. To the best of our knowledge, this is the first report of homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38).

Context. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder, which is characterized by renal phosphate wasting, hypercalciuria, increased 1,25-dihydroxyvitamin D, and decreased parathormone (PTH) levels. Objective. Here we report different clinical features of two siblings with HHRH, confirmed with molecular diagnosis. Subjects and methods. 16.4 years old boy (P1), and 8.7 years old girl (P2) were referred to our outpatient clinic due to clinical suspicion of metabolic bone diseases. Results. P1 had severe hypophosphatemia. Additionally, PTH concentration was near to the lower limit, 1,25-dihydroxyvitamin-D concentration was near to the upper limit. P2 had relatively milder clinical and laboratory findings. Bilateral renal calculi were detected on ultrasound in both of them. HHRH was suspected due to their described biochemistry and the presence of bilateral renal calculi. Molecular analysis of SLC34A3 gene revealed a homozygous variant c.756G>A (p.Gln252=) and a splice donor variant c.1335+2T>A. After oral phosphate treatment, clinical and biochemical improvements were observed. However treatment nonadherence of patients was a barrier to reach treatment goal Conclusion. The clinical phenotype due to the same mutation in the SLC34A3 gene may vary even among the members of the same family. An accurate diagnosis is important for the appropriate treatment.

Context. Pancreatic neuroendocrine tumours (PanNETs) are rare pancreatic neoplasms. PanNETs can be treated by multimodal approach including surgery, locoregional and systemic therapy. Objective. The aim of the present study is to evaluate predictive factors of overall survival in patients with PanNETs surgically treated at a single center. Subjects and methods. The study group consisted of 120 patients with PanNETs who had undergone surgery at the Center of Digestive Diseases and Liver Transplantation of Fundeni Clinical Institute, Bucharest, Romania. Surgical resection of the primary tumor was performed in 110 patients. Results. Tumor size > 2 cm (p=0.048) (90% CI) lymph node involvement (p=0.048), ENET grade (p<0.001), distant metastases (p<0.001), Ki 67 index (<2%, 2-5%, 5-10%, 10-20%, >20%) (p<0.001) were identified as significant prognostic factors for OS on univariate analysis. Using multivariate Cox proportional regression model we found that distant metastases and Ki 67 index were independent risk factors for the survival outcome. Conclusions. Surgery with curative intent should be considered in all cases if clinically appropriate and technically feasible. High grade (Ki67 index ≥10%) tumours were associated with a 2- fold increase in risk of death as compared to those with a Ki67 <10%

We report the case of a 55-year-old-male with a large cell metastatic pancreatic neuroendocrine carcinoma treated for 14 months with lanreotide autogel having a stable disease (SD) and not responding to chemotherapy. The somatostatin analogues (SSA) were introduced after an episode of diarrhea and controlled the disease. Progression-free survival (PFS) as determined by Computerized Tomography (CT) scans was obtained for 14 months. After more than a year, the patient’s health state deteriorated along with progressive disease. The capecitabine-temozolomide regimen was challenged, but after three cycles, a rapid clinical decline was noted. Conclusion. This unexpected event (diarrhea) in the course of the disease could represent the beginning of carcinoid syndrome. While the lanreotide autogel helped the episode of diarrhea pass, it also helped gain control over the disease itself.

The detection of thyroid nodules in a patient with Graves&#8217; disease is not a rare event.\r\nThe management of these cases still represents a controversial problem for clinical practice.\r\nThis paper describes the case of a patient with Graves&#8217; disease and a concurrent\r\nfollicular thyroid carcinoma, presenting as a clinical palpable nodule in the right lobe.\r\nThyroid function tests confirmed thyrotoxicosis. Immunological investigations showed high\r\nlevels of TSH-R antibodies. Thyroid ultrasound revealed an increased thyroid volume with\r\na diffuse low echogenicity of parenchyma and in the right lobe a single homogeneous\r\nhypoechoic nodule. The scintiscan indicated the presence of a &#8220;cold nodule&#8221; in the right lobe\r\nand increased uptake in the rest of parenchyma. Antithyroid drug therapy was\r\nrecommended. Cytological exam indicated an &#8220;indeterminate&#8221; smear. After euthyroidism\r\nwas achieved, surgical therapy was recommended and near total thyroidectomy was\r\nperformed. The morphopathological exam revealed an invasive follicular carcinoma on a\r\ndiffuse thyroid hyperplasia (Graves&#8217; disease). This case report is followed by a discussion\r\nabout the incidence of malignancy in thyroid nodules concurrent with Graves&#8217; disease. The\r\ncriteria that raised concern about a possible malignancy of the nodule are presented.\r\nIn conclusion, we recommend that patients with Graves&#8217; disease should undergo a\r\nregular examination of the thyroid gland for an early detection of possible malignant\r\nnodules. The intervention of choice in these cases should be near total or total\r\nthyroidectomy, if malignancy cannot be excluded by preoperative evaluation.

Complete heart block associated with hyperthyroidism is infrequent, and the diagnosis of hyperthyroidism is usually not considered in the absence of tachycardia. A 55-year-old woman was admitted to our emergency clinic with dizziness and syncope attack. Her electrocardiogram showed complete heart block.\r\nHyperthyroidism had been diagnosed, and she had been treated with propylthiouracil as an anti-thyroid treatment 3 years ago, although she had not taken this drug during the last 2 months. Her thyroid function tests showed hyperthyroidism. Antithyroid treatment was started again. Her rhythm returned from complete atrioventricular block to normal sinus rhythm\r\non the seventh day of hospitalization.

Aim. To evaluate the diagnostic performance of radiomics features of two-dimensional (2D) and threedimensional (3D) ultrasound (US) in predicting extrathyroidal extension (ETE) status in papillary thyroid carcinoma (PTC). Patients and Methods. 2D and 3D thyroid ultrasound images of 72 PTC patients confirmed by pathology were retrospectively analyzed. The patients were assigned to ETE and non-ETE. The regions of interest (ROIs) were obtained manually. From these images, a larger number of radiomic features were automatically extracted. Lastly, the diagnostic abilities of the radiomics models and a radiologist were evaluated using receiver operating characteristic (ROC) analysis. We extracted 1693 texture features firstly. Results. The area under the ROC curve (AUC) of the radiologist was 0.65. For 2D US, the mean AUC of the three classifiers separately were: 0.744 for logistic regression (LR), 0.694 for multilayer perceptron (MLP), 0.733 for support vector machines (SVM). For 3D US they were 0.876 for LR, 0.825 for MLP, 0.867 for SVM. The diagnostic efficiency of the radiomics was better than radiologist. The LR model had favorable discriminate performance with higher area under the curve. Conclusion. Radiomics based on US image had the potential to preoperatively predict ETE. Radiomics based on 3D US images presented more advantages over radiomics based on 2D US images and radiologist.

Background. Prior studies examining cyclic mastalgia and sex hormones have failed to\r\nreveal any specific endocrine cause and their results of them are inconsistent.\r\nAim. To evaluate luteal hormonal levels in women with marked premenstrual mastalgia\r\nin response to toremifene.\r\nMethods. In a double-blind crossover randomization procedure after one baseline cycle,\r\n32 women were randomized to receive 20 mg toremifene, and 30 women placebo from cycle\r\nday 15 until the next menstruation for three menstrual cycles. After a wash-out cycle the women\r\nwere crossed over to receive placebo and toremifene, respectively. The luteal hormonal levels\r\nwere measured at baseline, and during the third cycle of toremifene and placebo. The study was\r\nsetup in a general practice population from two Finnish hospital districts. Serum FSH, estradiol,\r\nprogesterone, prolactin, androstenedione, total and free testosterone were measured.\r\nResults. When all the toremifene-treated cycles were compared with all the placebo\r\ncycles and with the baseline, the median estradiol levels were 0.36, 0.27 and 0.31 nmol/L,\r\nrespectively (baseline versus toremifene, P=0.005; baseline versus placebo P=0.095; and\r\ntoremifene versus placebo P<0.001). The median progesterone levels were at baseline 32.5\r\nnmol/L, during placebo 34.5 nmol/L and during toremifene 42.5 nmol/L (baseline versus\r\ntoremifene P=0.002; baseline versus placebo P=0.802; and toremifene versus placebo\r\nP=0.002). The median prolactin level was significantly higher during the toremifene cycles\r\n(268 mU/L) as compared to the baseline (222 mU/L, P=0.046). There were no significant\r\nchanges in other hormone concentrations evaluated.\r\nConclusion. Toremifene seems to have a luteotropic effect in women suffering from\r\npremenstrual mastalgia.

Context. Polycystic ovary syndrome (PCOS) is associated with increased prevalence of preeclampsia (PE); microRNAs (miRs) could play an important role in the pathogenesis of PE and PCOS. Objective. To investigate the expression levels of miRs 155-5p and 518b in blood leukocytes of patients with PE and PCOS. Design. Using real-time quantitative PCR method, miR-155-5p and miR-518b were examined from PE, PCOS, PE+PCOS, and controls. Subjects and Methods. The relative expression of the target miRs in patient samples was compared to control samples. The results were calculated as relative quantification values. Results. Confounding variables were controlled using analyses for covariance. Significant differences were observed in miR-155-5p (p=0.008) and miRNA-518 (p=0.016) expression levels among the groups. miR-155- 5p (p=0.014) and miR-518b (p=0.036) were upregulated in PCOS patients and miR-518b (p=0.028) were increased in cases with PCOS+PE. Near significant difference was found (p=0.06) in miR-518b expression levels in cases with PE, compared to controls. miR-518b was observed to be positively correlated with alanine transaminase in cases with PE (r=0.80; P=0.017) and PE+PCOS (r=0.80, p=0.017). Conclusions. Our preliminary findings suggested that expression profiling of miR-155-5p and miR-518b in blood leukocytes were upregulated in pregnant women with PCOS. Moreover, miR-518b was found to be related to PE in cases with PCOS

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.