Plasma concentration and expression of adipokines in epicardial and subcutaneous adipose tissue are associated with impaired left ventricular filling pattern.

BACKGROUND: Adipokines in serum derive mainly from subcutaneous and visceral adipose tissues. Epicardial adipose tissue (EAT), being a relatively small but unique fat depot, probably does not make an important contribution to systemic concentrations of adipokines. However, proximity of EAT to cardiac muscle and coronary arteries allows cells and proteins to penetrate between tissues. It is hypothesized that overexpression of proinflammatory cytokines in EAT plays an important role in pathophysiology of the heart. The aim of the study was to analyze the relationship between echocardiographic heart parameters and adipokines in plasma, epicardial, and subcutaneous fat in patients with obesity and type 2 diabetes mellitus (T2DM). Additionally, we evaluate proinflammatory properties of EAT by comparing that depot with subcutaneous adipose tissue. METHODS: The study included 55 male individuals diagnosed with coronary artery disease (CAD) who underwent planned coronary artery bypass graft. Plasma concentrations of leptin, adiponectin, resistin, visfatin, apelin, IL-6, and TNF-α, as well as their mRNA and protein expressions in EAT and subcutaneous adipose tissue (SAT) were determined. RESULTS: Obesity and diabetes were associated with increased leptin and decreased adiponectin plasma levels, higher protein expression of leptin and IL-6 in SAT, and higher visfatin protein expression in EAT. Impaired left ventricular (LV) diastolic function was associated with increased plasma concentrations of leptin, resistin, IL-6, and adiponectin, as well as with increased expressions of resistin, apelin, and adiponectin in SAT, and leptin in EAT. CONCLUSIONS: Obesity and T2DM in individuals with CAD have a limited effect on adipokines. Expression of adipokines in EAT and SAT is linked to certain heart parameters, however diastolic dysfunction of the LV is strongly associated with circulating adipokines.

NETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease.

BACKGROUND: There are no effective biomarkers for the management of bronchopulmonary carcinoids (BPC). We examined the utility of a neuroendocrine multigene transcript "liquid biopsy" (NETest) in BPC for diagnosis and monitoring of the disease status. AIM: To independently validate the utility of the NETest in diagnosis and management of BPC in a multicenter, multinational, blinded study. MATERIAL AND METHODS: The study cohorts assessed were BPC (n = 99), healthy controls (n = 102), other lung neoplasia (n = 101) including adenocarcinomas (ACC) (n = 41), squamous cell carcinomas (SCC) (n = 37), small-cell lung cancer (SCLC) (n = 16), large-cell neuroendocrine carcinoma (LCNEC) (n = 7), and idiopathic pulmonary fibrosis (IPF) (n = 50). BPC were histologically classified as typical (TC) (n = 62) and atypical carcinoids (AC) (n = 37). BPC disease status determination was based on imaging and RECIST 1.1. NETest diagnostic metrics and disease status accuracy were evaluated. The upper limit of normal (NETest) was 20. Twenty matched tissue-blood pairs were also evaluated. Data are means ± SD. RESULTS: NETest levels were significantly increased in BPC (45 ± 25) versus controls (9 ± 8; p < 0.0001). The area under the ROC curve was 0.96 ± 0.01. Accuracy, sensitivity, and specificity were: 92, 84, and 100%. NETest was also elevated in SCLC (42 ± 32) and LCNEC (28 ± 7). NETest accurately distinguished progressive (61 ± 26) from stable disease (35.5 ± 18; p < 0.0001). In BPC, NETest levels were elevated in metastatic disease irrespective of histology (AC: p < 0.02; TC: p = 0.0006). In nonendocrine lung cancers, ACC (18 ± 21) and SCC (12 ± 11) and benign disease (IPF) (18 ± 25) levels were significantly lower compared to BPC level (p < 0.001). Significant correlations were evident between paired tumor and blood samples for BPC (R: 0.83, p < 0.0001) and SCLC (R: 0.68) but not for SCC and ACC (R: 0.25-0.31). CONCLUSIONS: Elevated -NETest levels are indicative of lung neuroendocrine neoplasia. NETest levels correlate with tumor tissue and imaging and accurately define clinical progression.

Baseline chromogranin A and its dynamics are prognostic markers in gastroenteropancreatic neuroendocrine tumors.

AIM: This study assessed whether absolute chromogranin A (CgA) values at various stages of treatment have prognostic value in patients with pancreatic and midgut neuroendocrine tumors, subjected to peptide receptor radionuclide therapy with 90Y-[DOTA0, D-Phe1, Tyr3]-octreotate. PATIENTS & METHODS: CgA was determined before peptide receptor radionuclide therapy, 6 weeks, 6, 12, 18 and 24 months after the last dose of 90Y-[DOTA0, D-Phe1, Tyr3]-octreotate. The primary end point was overall survival. RESULTS: Elevated baseline CgA concentrations and their relative increase within the first year of observation were unfavorable predictors of overall survival, but not progression. CONCLUSION: Even a single baseline measurement of CgA can be useful in establishing prognosis in this group, if this parameter exceeds its upper normal limit more than tenfold.

Epidemiology, risk factors and prognosis of Interferon alpha induced thyroid disorders. A Prospective Clinical Study.

INTRODUCTION: Hepatitis C virus (HCV) infection is a worldwide problem and hepatitis, which is its natural unfavourable course, is still a challenge for hepatologist. At present, standards of treatment are changing from combined therapy with interferon alpha (IFN-α) and ribavirin to new antiviral drugs. The current classification divides interferon induced thyroid diseases (IITD) into two groups: autoimmune (Hashimoto disease, Graves disease, positive antithyroid autoantibodies in euthyroid patients) and non-autoimmune (destructive thyroiditis, non-autoimmune hypothyroidism). A common complication of cytokine therapy is the induction of antithyroid autoantibodies de novo without thyroid dysfunction. During therapeutic regimens combined with ribavirin, destructive thyroiditis with typical biphasic course is more common than in IFN-α monotherapy. Clinically, overt pathologies often have discrete symptoms, which cause diagnostic and therapeutic dilemmas. AIMS: The aim of this study was to estimate IITD occurrence, to find risk factors for IITD development. MATERIAL AND METHODS: The study group consisted of 66 patients treated for HCV infection. Before and during antiviral therapy, hormonal (TSH, fT4, fT3), immunological (thyroid autoantibodies), ultrasonographic and genetic (HLA-A2) parameters were evaluated. RESULTS: Hormonal disturbances were detected in 24.2% of patients; however, 43.9% of patients had positive thyroid autoantibodies (de novo) without hormonal imbalance. Multivariate analysis revealed the following: female sex, elevated TSH level, occurrence of anti-TPO autoantibodies (TPO-Ab), and increased blood velocity in thyroid arteries are risk factors for IITD development. IN CONCLUSION: Thyroid disorders are common during IFN-α therapy. Previous epidemiological data seem to be underestimated. Important risk factors for IITD development are: female sex, elevated serum TSH concentration (≥2.5 µU/mL), positive TPO-Ab and increased blood velocity in thyroid arteries.

Long-term efficacy of (90)Y-DOTATATE in patients with nonresectable pancreatic and small bowel neuroendocrine neoplasms.

AIM: To determine the efficacy of (90)Y [DOTA(0), D-Phe(1), Tyr(3)]-octreotate (DOTATATE) in 67 patients with pancreatic and small bowel neuroendocrine tumors (NETs). PATIENTS & METHODS: The primary efficacy end point was overall survival (OS) and secondary end points were progression-free survival (PFS) and tumor response. RESULTS: Median PFS in pancreatic and small bowel NETs was 25 and 28 months, respectively, and median OS was 42 and 38.5 months, respectively. No intergroup differences in median OS (p = 0.945) or PFS (p = 0.174) were found, also after adjustment for tumor origin, secretory status and grade, and patient's gender. CONCLUSION: (90)Y-DOTATATE may have similar efficacy in pancreatic and small bowel NETs. Better WHO performance status at baseline seems to be associated with more favorable outcomes.

Evaluation of Head and Neck Paragangliomas by Computed Tomography in Patients with Pheochromocytoma-Paraganglioma Syndromes.

BACKGROUND: Hereditary head and neck paragangliomas (HNP) are very often associated with pheochromocytoma-paraganglioma syndromes, which are caused by mutations in genes encoding subunits of succinate dehydrogenase (SDHx) complex. The aim of this study was to determine the frequency and location of HNP among SDHx carriers. MATERIAL/METHODS: A total of 72 patients with SDHx mutations underwent computed tomography examinations of the head and neck. HNP were present in 44 (61.1%) out of 72 patients (31 SDHD, 11 SDHB, 2 SDHC); 113 HNP were found; the most common were carotid paragangliomas (59) and vagal paragangliomas (27). RESULTS: The HNP were statistically more frequent in carriers of SDHD mutations compared to carriers of SDHB mutations (72.1% vs. 43.5%, p=0.033). Multiple tumors more often occurred in patients with SDHD mutations 26/31 (83.9%) than in patients with SDHB mutations 6/11 (54.5%) p=0.05. There was a significant difference in the prevalence of carotid paragangliomas between patients with SDHB and SDHD mutations (7/11 [63.6%] vs. 30/31 [96.8%], respectively, p=0.004). Patients with SDHD mutations more often had carotid paragangliomas located on the left side than on the right side, as compared to SDHB mutations 25/31 (80.6%) vs. 4/11 (36.4%), p=0.006. CONCLUSIONS: SDHx mutations predispose to multifocal and bilateral HNP. Carotid and vagal paragangliomas occurred most often. Patients with SDHD mutations are characterized by higher frequency of HNP than patients with SDHB mutations, which is mainly driven by higher frequency of carotid body tumors in patients with SDHD mutations. No difference in the frequency of head and neck paragangliomas in other locations was found.

US not bright but right method of thyroid volume estimation even in large and substernal extended goitres. Comparison of US and three methods of CT thyroid evaluation ­ prospective study.

BACKGROUND: Ultrasound is nowadays a method of choice for thyroid volume assessment. However, its disadvantage is some inaccuracy, which is said to be higher in huge, especially substernally extended goitres. AIMS: The aim of the study was to compare the US and CT thyroid volumetric measurements: multi-observers (CT MO) and one-observer (CT OO) to CT planimetry results (CT Pl) in patients with large goitres. MATERIALS & METHODS: The study material comprised 70 thyroid imaging examinations obtained from 35 patients with nontoxic goitres, scanned twice before and after radioiodine treatment. Mean thyroid volume was 88·97 ± 60·21 ml. Thirty-three thyroid scans revealed the extension below the jugular notch (mean of 2·46 cm). Thyroid volume in US, CT MO and CT OO was estimated using the ellipsoid formula. CT Pl was established a reference method. RESULTS: The mean thyroid volume in CT Pl was 88·97 ml (median 80·73, range 11·81 to 315·97). US underestimates thyroid volume by 7·55 ml (7·7%) with a sufficient correlation (R(2) = 0·89) and precision (20·37). CT OO is the closest and CT MO the most distant from CT Pl, with US between them in thyroid volume estimation. The percentage US bias is constant through all range of thyroid volume. There is no difference for percentage bias between US and CT Pl for goitres with (8·67%), and without (6·70%) substernal part. CONCLUSION: US examination is sufficient for epidemiological studies, radioiodine activity calculation and goitre size assessment in everyday medical practice. Neither initial size of the goitre nor its substernal extension affects US assessment precision.

Usefulness of Somatostatin Receptor Scintigraphy (Tc-[HYNIC, Tyr3]-Octreotide) and 123I-Metaiodobenzylguanidine Scintigraphy in Patients with SDHx Gene-Related Pheochromocytomas and Paragangliomas Detected by Computed Tomography.

AIMS: The aim of this study was to assess the usefulness of somatostatin receptor scintigraphy (SRS) using (99m)Tc-[HYNIC, Tyr3]-octreotide (TOC) and 123I-metaiodobenzylguanidine (mIBG) in patients with SDHx-related syndromes in which paragangliomas were detected by computed tomography and to establish an optimal imaging diagnostic algorithm in SDHx mutation carriers. METHODS: All carriers with clinical and radiological findings suggesting paragangliomas were screened by SRS and 123I-mIBG. Lesions were classified by body regions, i.e. head and neck, chest, abdomen with pelvis and adrenal gland as well as metastasis. RESULTS: We evaluated 46 SDHx gene mutation carriers (32 index cases and 14 relatives; 28 SDHD, 16 SDHB and 2 SDHC). In this group, 102 benign tumors were found in 39 studied patients, and malignant disease was diagnosed in 7 patients. In benign tumors, the sensitivity of SRS was estimated at 77% and of 123I-mIBG at 22.0%. The SRS and mIBG sensitivity was found to be clearly region dependent (p < 0.001). The highest SRS sensitivity was found in head and neck paragangliomas (HNP; 91.4%) and the lowest was found in abdominal paragangliomas and pheochromocytomas (40 and 42.9%, respectively). The highest 123I-mIBG sensitivity was found in pheochromocytomas (sensitivity of 100%) and the lowest in HNP (sensitivity of 3.7%). In metastatic disease, SRS was superior to mIBG (sensitivity of 95.2 vs. 23.8%, respectively). CONCLUSION: SRS and 123I-mIBG single photon emission computed tomography (SPECT) sensitivity in SDHx patients is highly body region dependent. In malignant tumors, SRS is superior to 123I-mIBG SPECT.

Blood flow velocity in the middle cerebral artery during transnasal endoscopic skull base surgery performed in controlled hypotension.

BACKGROUND AND PURPOSE: To assess blood flow velocity in the middle cerebral artery (MCA) during transnasal endoscopic procedures performed with decreased hemodynamic parameters. MATERIALS AND METHODS: In 40 patients who underwent endoscopic skull base surgery in controlled hypotension (studied group) and in 13 patients operated without reduction of hemodynamic parameters (control group), blood flow velocity in MCA was assessed with transcranial color Doppler sonography. RESULTS: Blood flow velocity in MCA remained within the range of age-specific reference values in all patients before operation. It decreased significantly in both groups after induction of anesthesia and then dropped even further in studied group of patients when hemodynamic parameters were reduced; the systolic velocity fell below the normal reference values in 25% of patients, the mean velocity in 50% and the diastolic velocity in 57% of patients. The diastolic velocity was much more heavily influenced by diminished hemodynamic parameters than systolic velocity in the studied group as opposed to the control group where reduction of blood flow velocity pertained equally systolic and diastolic velocity. CONCLUSION: During transnasal endoscopic procedures performed in moderate hypotension, in addition to significant drop of blood flow velocity to values well below the normal reference range, a divergent reduction of systolic and diastolic velocity was detected. Since divergent systolic and diastolic velocity may indicate an early phase of cerebral autoregulation compromise, and the decrease of mean blood flow velocity in MCA corresponds with a decrease of cerebral blood flow, further investigations in this field seem warranted.

Chemometric evaluation of urinary steroid hormone levels as potential biomarkers of neuroendocrine tumors.

Neuroendocrine tumors (NETs) are uncommon tumors which can secrete specific hormone products such as peptides, biogenic amines and hormones. So far, the diagnosis of NETs has been difficult because most NET markers are not specific for a given tumor and none of the NET markers can be used to fulfil the criteria of high specificity and high sensitivity for the screening procedure. However, by combining the measurements of different NET markers, they become highly sensitive and specific diagnostic tests. The aim of the work was to identify whether urinary steroid hormones can be identified as potential new biomarkers of NETs, which could be used as prognostic and clinical course monitoring factors. Thus, a rapid and sensitive reversed-phase high-performance liquid chromatographic method (RP-HPLC) with UV detection has been developed for the determination of cortisol, cortisone, corticosterone, testosterone, epitestosterone and progesterone in human urine. The method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The limits of detection and quantification were 0.5 and 1 ng mL-1 for each steroid hormone, respectively. Linearity was confirmed within a range of 1-300 ng mL-1 with a correlation coefficient greater than 0.9995 for all analytes. The described method was successfully applied for the quantification of six endogenous steroid levels in human urine. Studies were performed on 20 healthy volunteers and 19 patients with NETs. Next, for better understanding of tumor biology in NETs and for checking whether steroid hormones can be used as potential biomarkers of NETs, a chemometric analysis of urinary steroid hormone levels in both data sets was performed.

Assessment of real-world usage of lanreotide AUTOGEL 120 in Polish acromegalic patients - results from the prospective 12-month phase of Lanro-Study.

AIM OF THE STUDY: To assess resource utilization and costs of treatment with lanreotide AUTOGEL 120 mg (ATG120) administered as part of routine acromegaly care in Poland. MATERIAL AND METHODS: A multicentre, non-interventional, observational study on resource utilization in Polish acromegalic patients treated with ATG120 at 4 weeks or extended (> 4 weeks) dosing interval. The study recruited adult acromegalic patients treated medically for ≥ 1 year including at least 3 injections of ATG120. Data on dosing interval, aspects of administration, and resource utilization were collected prospectively during 12 months. Costs were calculated in PLN from the public health-care payer perspective for the year 2013. RESULTS: 139 patients were included in the analysis. Changes in dosing regimen were reported in 14 (9.4%) patients. Combined treatment was used in 11 (8%) patients. Seventy patients (50%) received ATG120 at an extended dosing interval; the mean number of days between injections was 35.56 (SD 8.4). ATG120 was predominantly administered in an out-patient setting (77%), by health-care professionals (94%). Mean time needed for preparation and administration was 4.33 and 1.58 min, respectively, mean product wastage - 0.13 mg. Patients were predominantly treated in an out-patient setting with 7.06 physician visits/patient/year. The most common control examinations were magnetic resonance imaging of brain and brain stem (1.36/patient/year), ultrasound of the neck (1.35/patient/year), GH (1.69/patient/year), glycaemia (1.12/patient/year), IGF-1 (0.84/patient/year), pituitary-thyroid axis hormone levels assessment (TSH-0.58/patient/year, T4-0.78/patient/year). There were 0.43 hospitalizations/patient/year. For direct medical costs estimated at PLN 50 692/patient/year the main item was the costs of ATG120 (PLN 4103.87/patient/month; 97%). The mean medical cost, excluding pharmacotherapy, was PLN 1445/patient/year (out-patient care - 49%, hospitalization - 23%, diagnostics/laboratory tests - 28%). CONCLUSIONS: These results represent the current use of ATG120 in the population of Polish acromegalic patients in a realistic clinical setting. Findings that 50% of patients could be treated with dose intervals of longer than 28 days support the potential of ATG120 to reduce the treatment burden.

The clinical value of MRI using single-shot echoplanar DWI to identify liver involvement in patients with advanced gastroenteropancreatic-neuroendocrine tumors (GEP-NETs), compared to FSE T2 and FFE T1 weighted image after i.v. Gd-EOB-DTPA contrast enhancement.

BACKGROUND: To assess the detection rate of liver lesions in patients with advanced gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs) using echo planar (EP) DWI (diffusion weighted imaging) as compared to standard FSE T2 wi and FFE T1 wi with i.v. (Gd-EOB)-DTPA. MATERIAL/METHODS: This prospective single-institution study included 55 patients with liver involvement confirmed by GEP-NETs 1.5T MRI system, using FSE T2, EP DWI and FFE T1 with i.v. (Gd-EOB)-DTPA. The potential differences between detection rates of liver deposits using 3 different MR approaches and between groups of patients were compared. RESULTS: Mean number of liver deposits: FSE T2=20.7, FFE T1=25.7 and tested EP DWI=24.0. No significant difference was found in overall detection rate of liver deposits seen in 3 different techniques. A significant difference in detection rate of liver deposits was noted between male vs. female and secreting vs. non-secreting cancers. There was nearly perfect agreement between both observers, and each of the tested MRI approaches in regards to number of detected liver lesions (Cohen's kappa=0.848-1). CONCLUSIONS: There were no significant differences among the 3 different MRI approaches in detection rates of liver deposits. Perfect agreement with high detection rate of liver deposits provides a rationale for the use of EP DWI in follow-up studies in GEP-NET patients.

Delayed diagnosis of adrenal hypoplasia congenita in a patient with a new mutation in the NR0B1 gene.

Determining the precise cause of adrenal insufficiency occurring in infancy is of critical importance for both the correct management of affected children and the provision of correct genetic advice to their families. We report a case of a 24-year-old, male patient bearing a new mutation in the DAX1 gene. The patient was born at term, from a healthy pregnancy. Adrenal insufficiency was diagnosed in the fourth week of life with a salt-wasting syndrome, but it was mistakenly believed to be secondary to congenital adrenal hyperplasia (CAH). On hydrocortisone substitution, the child continued to develop normally, but the diagnosis of CAH was questioned, which led to an episode of an abrupt withdrawal of hydrocortisone substitution and subsequently caused a reoccurrence of a life-threatening salt-wasting syndrome. Owing to close follow-up, the patient's gonadal axis deficiency was promptly identified, which allowed an assisted but successful onset of puberty. We proposed the diagnosis of adrenal hypoplasia congenita (AHC) in this patient and identified a hemizygous mutation (c.1130delAinsGT, p.E377GfsX12) in exon 1 of the NR0B1 gene. To our knowledge, the detected mutation has not been described previously (HGMD Professional 2010.4, Human Gene Mutation Database, Biobase, Beverly, MA, USA). It leads to a frameshift, a premature stop codon, and, most likely, non-sense-mediated decay of the mutant mRNA. In this case, close patient follow-up minimized the detrimental consequences of an incorrect diagnosis. Nevertheless, it highlights the importance of the early precise diagnosis of patients with AHC.

Molecular identification of bronchopulmonary neuroendocrine tumours and neuroendocrine genotype in lung neoplasia using the NETest liquid biopsy.

OBJECTIVES: Diagnosing lung neuroendocrine neoplasia (NEN) requires a biopsy or an operation. We evaluated a 'liquid biopsy' (NETest) as an in vitro diagnostic tool for identifying NEN and compared it to chromogranin A (CgA). METHODS: We identified 4 study cohorts: patients with bronchopulmonary carcinoids (n = 99, including 62 typical and 37 atypical carcinoids), lung cancers [n = 101, including 41 adenocarcinomas, 37 squamous carcinomas (SQC), 16 small-cell lung cancers and 7 large-cell neuroendocrine carcinomas]; benign disease (50 idiopathic pulmonary fibrosis) and healthy controls (n = 102). Transcript levels measured quantitatively (activity scores: 0-100) were compared to CgA (enzyme-linked immunosorbent assay; normal < 109 ng/ml) levels. RESULTS: The results of the NETest were positive (>20) in 94% of patients with bronchopulmonary carcinoid compared to 8% of the controls (Fisher's exact test; P < 0.001) and were significantly more accurate as a diagnostic test (McNemar's test; P < 0.001, χ2 = 72) than was CgA (positive: 19% bronchopulmonary carcinoid, 15% controls). Small-cell lung cancers (87%), large-cell neuroendocrine carcinomas (86%), adenocarcinoma (42%) and SQC (35%) were also NETest-positive. Increasing the NETest cut-off score to >40 was useful for detecting all NENs and differentiating these tumours from either controls/benign lung diseases (specificity 97%) or adenocarcinoma/SQC (specificity 94%). CgA was positive in 15-44% irrespective of pathology and had no diagnostic value. CONCLUSIONS: A gene-based liquid biopsy is an effective and accurate method for diagnosing lung tumours with neuroendocrine gene expression. CgA has no value. An NETest score >40 provides an accurate (94-97%) rule-in for the diagnosis of NEN and a rule-out for benign and other neoplastic diseases. Because neuroendocrine gene expression is associated with a poor prognosis, NETest levels may have utility both in the diagnosis of and the treatment stratification for lung neoplasia.

[Apicoaortic valved conduit as an alternative method of surgical treatment of aortic stenosis - a case report]. / Wszczepienie protezy zaopatrzonej w zastawke pomiedzy koniuszkiem lewej komory a aorta zstepujaca jako alternatywna metoda operacji zwezenia zastawki aortalnej - opis przypadku.

A case of a 73-year-old patient with critical aortic stenosis, porcelain aorta and occluded femoral arteries is presented. We performed apico-aortic valved conduit (A-AVC) without cardiopulmonary bypass (CPB). Hegar dilator inserted through the apex into the left ventricle allowed anastomosis of dacron tube to the apex. Valved conduit was anastomosed to the descending aorta. Both tubes were connected. Before the operation, maximal gradient through the valve was 95, after operation dropped to 33 mmHg. This method of apical anastomosis allowed to perform A-AVC without CPB in a patient with extremely high peri-operative risk while using CPB.

Impact of screening kindreds for SDHD p.Cys11X as a common mutation associated with paraganglioma syndrome type 1.

CONTEXT AND OBJECTIVE: Germline mutations of the genes SDHB, SDHC, and SDHD predispose to paraganglioma syndromes. Mutation-specific counseling, risk assessment, and management recommendations ideally should be performed. Here, we provide data for a single common mutation of the SDHD gene. METHODS: The European-American Pheochromocytoma-Paraganglioma Registry served as the source for unrelated index cases affected by pheochromocytoma or paraganglioma. Patients with the SDHD c.33 C-->A (p.Cys11X) germline mutations were reinvestigated by whole-body magnetic resonance imaging and 24-h urinary catecholamine assay. First-degree relatives underwent genetic testing and those testing positive had same clinical investigations. Microsatellite analyses were used to test the hypothesis that all index cases were related and the mutation is a founding one. RESULTS: Sixteen index cases with the mutation SDHD p.Cys11X are registered. After testing their relatives, there were a total of 25 mutation carriers. We excluded seven subjects who inherited the mutation from the mother because of maternal imprinting. Thus, 18 mutation carriers were clinically affected. Among these 16 (89%) had head and neck paragangliomas, six (33%) thoracic tumors, six (33%) extraadrenal retroperitoneal, and five (28%) intraadrenal. Of note, 16 (89%) had multiple tumors at first diagnosis, and one (5%) had signs of malignancy during follow-up. Overall penetrance was 100% at age 54. Haplotype analyses revealed evidence for a founder effect. CONCLUSIONS: The SDHD p.Cys11X mutation is a founding mutation associated with a high penetrance for paraganglial tumors of the skull base, neck, thorax, and retroperitoneum in the first four decades of life and, rarely, with malignancy.

[Right atrial tumour in a patient with chest pain - a case report]. / Patologiczny twór w prawym przedsionku u kobiety z bólami w klatce piersiowej.

Intracardiac masses present an important problem in cardiology. Echocardiography became a main non-invasive diagnostic method in identifying these abnormalities. Most often there are thrombuses, less often - vegetations in course of infective endocarditis, and rarely - tumours or congenital abnormalities. This case report presents difficulties in diagnosing intracardiac mass in a 70-year-old female presenting with atypical chest pain.

[Insulinoma misdiagnosed and treated as epilepsy]. / Wyspiak trzustki mylnie rozpoznany i leczony jako padaczka--opis przypadku.

Although insulinoma constitutes almost 90% of neuroendocrine tumors localized in the pancreas, it is a rare disease. Quite commonly prior to the diagnosis there is a history of several years and misdiagnosis as neurological or cardiological disease is not infrequent. Patient, 22 years old, since 7 years experiencing multiple incidents of neuroglycopenia with concurrent hyperadrenergic reaction. Consciousness disturbances and muscle tremor together with feeling of hunger and tachycardia occurred mainly in the morning hours, or after physical exercise, and subsided after glucose intake. Increase in body weight, typical for insulinoma, was also observed. The patient was hospitalized twice in Pediatric Department and although hypoglycemia was observed, no additional testing was performed to exclude insulinoma; reported symptoms and abnormalities in EEG recording after provocation resulted in diagnosis and treatment of epilepsy. During hospitalization in the Department of Endocrinology fasting test was performed, which revealed inadequately high insulin level with glucose level of 41 mg% and signs of neuroglycopenia. The image of pancreas was normal in the acquired abdominal ultrasound and in CT a tumor was found in the tail of pancreas. The patient underwent laparoscopic operation and the clinical diagnosis was confirmed by histopathology. Antiepileptic drugs were discontinued. Total remission of symptoms was achieved. The presented case demonstrates the difficulties in correct interpretation of reported symptoms, while the results of biochemical tests and imaging studies point precisely to the diagnosis. Focal neurological signs resulting from multiple episodes of hypoglycemia may lead to misdiagnosis and treatment of epilepsia.

Nontoxic Goiter (NTG) and Radioiodine: What Do Patients Think About It? Quality of Life in Patients with NTG Before and After 131-I Therapy.

OBJECTIVE: Despite numerous publications regarding nontoxic goiter (NTG) treatment and an increasing interest in patients' quality of life, few studies present the outcome of 131-I treatment from the patients' perspective. Our study's main aim was to verify whether there is any improvement in life quality following 131-I treatment. MATERIALS AND METHODS: Thirty-five patients with NTG qualified to participate in the study. All patients completed a Thyroid-Related Health-Related Quality of Life (Thy-R-HRQoL) questionnaire created by us and the Medical Outcomes Study 36-item Short Form (SF-36), right before and 1 year after 131-I. RESULTS: We observed an improvement in six out of eight SF-36 and three out of seven Thy-R-HRQoL domains. In comparison with the control group, we observed worse results in two out of eight, prior to treatment, and one out of eight SF-36 afterward, as well as in all Thy-R-HRQoL domains. We did not find any correlation between improvement of Thy-R-HRQoL and SF-36 and goiter size reduction, except for Bodily Pain. There was also no correlation between improvement of SF-36 and Thy-R-HRQoL domains, and goiter size before treatment. The older the patient, the less noticeable improvement was observed in Physical and Social Functioning, and Vitality in SF-36, but age had no influence on the assessment by Thy-R-HRQoL. CONCLUSION: Radioiodine treatment improves life quality in patients with NTG. Use of the Health-Related Quality of Life questionnaire should be taken into consideration when evaluating life quality of patients with NTG. Relentless pursuit of maximal goiter size reduction in 131-I treatment is worth consideration. In our study, life quality improvement did not depend directly on the goiter size reduction. Life quality improvement after 131-I might not depend on initial goiter size, and for certain domains of SF-36 might be less clearly expressed in older patients.

Frequent expression of somatostatin receptor 2a in olfactory neuroblastomas: a new and distinctive feature.

Olfactory neuroblastoma (ONB) is a malignant neuroendocrine neoplasm with a usually slow course, but with considerable recurrence rate. Many neuroendocrine tumors have shown good response to the treatment with somatostatin analogs and somatostatin radioreceptor therapy. In ONBs, there are scarce data on somatostatin-based treatment and the cellular expression of somatostatin receptors (SSTR), the prerequisite for binding and effect of somatostatin on normal and tumor cells. The aim of our study was to investigate the immunohistochemical expression of SSTR2A and SSTR5 in a cohort of 40 ONBs. In addition, tissue microarrays containing 40 high-grade sinonasal carcinomas as well as 6 sinonasal lymphomas, 3 rhabdomyosarcomas, and 3 Ewing sarcomas were evaluated. Volante system was applied for staining evaluation. Thirty cases (75%) were immunopositive for SSTR2A and 3 (7.5%) for SSTR5. Among the 30 SSTR2A-positive ONBs, 19 tumors (63.3%) scored 2+ and 11 (36.7%) scored 3+. All SSTR5-positive ONBs scored 2+. Neither sinonasal carcinomas nor sinonasal small round blue cell neoplasms expressed SSTR2A or SSTR5. The frequent expression of SSTR2A provides a rationale for radioreceptor diagnosis and therapy with SST analogs in ONBs. SSTR2A expression in ONBs is a helpful adjunct in the differential diagnosis of ONBs.