The clinical utility of circulating neuroendocrine gene transcript analysis in well-differentiated paragangliomas and pheochromocytomas.

CONTEXT: Paragangliomas and pheochromocytomas (PPGLs) exhibit variable malignancy, which is difficult to determine by histopathology, amine measurements or tissue genetic analyses. OBJECTIVE: To evaluate whether a 51-neuroendocrine gene blood analysis has clinical utility as a diagnostic and prognostic marker. DESIGN: Prospective cohort study. Well-differentiated PPGLs (n = 32), metastatic (n = 4); SDHx mutation (n = 25); 12 biochemically active, Lanreotide treated (n = 4). Nine patients had multiple sampling. Age- and gender-matched controls and GEP-NETs (comparators). METHODS: Circulating neuroendocrine tumor mRNA measured (qPCR) with multianalyte algorithmic analysis. Metabolic, epigenomic and proliferative genes as well as somatostatin receptor expression were assessed (averaged, normalized gene expression: mean ± s.e.m.). Amines were measured by HPLC and chromogranin A by ELISA. Analyses (2-tailed): Fisher's test, non-parametric (Mann-Whitney), receiver-operator curve (ROC) and multivariate analysis (MVA). All data are presented as mean ± s.e.m. RESULTS: PPGL were NETest positive (100%). All exhibited higher scores than controls (55 ± 5% vs 8 ± 1%, P = 0.0001), similar to GEP-NETs (47 ± 5%). ROC analysis area under curve was 0.98 for differentiating PPGLs/controls (cut-off for normal: 26.7%). Mutation status was not directly linked to NETest. Genetic and molecular clustering was associated (P < 0.04) with NETest scores. Metastatic (80 ± 9%) and multicentric (64 ± 9%) disease had significantly (P < 0.04) higher scores than localized disease (43 ± 7%). Progressive disease (PD) had the highest scores (86 ± 2%) vs stable (SD, 41 ± 2%) (P < 0.0001). The area under the curve for PD from SD was 0.93 (cut-off for PD: 53%). Proliferation, epigenetic and somatostatin receptor gene expression was elevated (P < 0.03) in PD. Metabolic gene expression was decreased in SDHx mutations. Repeat NETest measurements defined clinical status in the 9 patients (6 SD and 3 PD). Amine measurement was non-informative. Multivariate analysis identified NETest >53% as an independent prognostic factor. CONCLUSION: Circulating NET transcript analysis is positive (100% diagnostic) in well-differentiated PCC/PGL, scores were elevated in progressive disease irrespective of mutation or biochemical activity and elevated levels were prognostic.

Effect of on-pump versus off-pump coronary bypass surgery on cardiac function assessed by intraoperative transesophageal echocardiography.

PURPOSE: To compare cardiac function assessed by intraoperative transesophageal echocardiography in patients undergoing cardiac revascularization with or without cardiopulmonary bypass. MATERIAL AND METHODS: Forty-one patients scheduled for elective, isolated cardiac revascularization (21 on-pump and 20 off-pump) were prospectively analyzed. Patients were matched for demographic (age and gender), anthropometric (BMI), clinical (co-morbidities, EuroScore) and laboratory variables (blood counts, renal function, left ventricular function). Transesophageal echocardiography was performed after induction of anesthesia, protamine sulfate administration, and chest closure. Left ventricular wall motion score index, end-diastolic area, fractional area change, right ventricular area change and end-diastolic area were assessed. Troponin I and C-reactive protein concentrations were measured. RESULTS: Regarding echocardiographic parameters of left and right ventricular function no significant differences between on-pump and off-pump groups at any point-of-time measurements were found. Troponin I and C-reactive protein were higher in on-pump as compared to off-pump group (p=0.001 and p=0.002; p=0.003 and p=0.001, respectively). CONCLUSIONS: In elective patients scheduled for cardiac revascularization there were no difference in cardiac performance assessed by intraoperative echocardiography regardless of surgical method used.

Giving radioiodine? Think about airport security alarms.

An increased sensitivity of airport detectors, a growing number of isotopic tests, and globalization of the society have raised a number of false positive radioactive alarms at airports and public places. This paper presents two new cases of patients who triggered airport security alarms after receiving 740MBq of (131)I for non-toxic goitre and attempts to compare surprisingly limited literature concerning this problem. A 57-year-old man triggered a security alarm at three different airports on the 17th, 28th, and 31st day after radioiodine exposure. Interestingly enough, in the meantime, on the 18th and 22nd day, no radiation was detected in him at the airport where he was twice detained as a source of radiation later on. The second case presents a 45-year-old woman who activated security alarm detectors while crossing a border on her coach trip 28 days after radioiodine administration.

Silent pulmonary embolism in a patient with acute myocardial infarction and type B acute aortic dissection - a case report.

A 69-year-old man while being treated for type B aortic dissection was also found to have acute myocardial infarction. The patient initially was treated conservatively. Prophylactic anticoagulant treatment of potential thrombosis was not given because of aortic dissection. Stent-graft implantation to the thoracic aorta was considered at the time. Unexpectedly, elective computer tomography (CT), revealed 2 large thrombi at the bifurcation of the pulmonary trunk. The patient did not show any symptoms of pulmonary embolism. Heparin therapy was initiated immediately. The patient responded well to the therapy and on transesophageal echocardiography and subsequent CT no embolic material was found. Since that time, the patient is receiving oral anticoagulation. The case we present raises the question of anticoagulation prophylaxis in the presence of aortic dissection in bedridden patients. Failure to use such therapy in our patient could have resulted in an unfavorable clinical outcome.

Ectopic ACTH syndrome associated with ovarian steroid-cell tumor.

Several cases of ovarian neoplasms resulting in Cushing's syndrome due to ectopic secretion of ACTH or ectopic secretion of F have been reported. Tumors producing ACTH include adenocarcinoma, androblastoma, Sertoli cell carcinoma, carcinoid tumor and teratoma. Cortisol secretion has been reported in ovarian steroid cell tumor (unclassified steroid cell tumor). We present a case of a 19-year-old woman with Cushing's syndrome in course of an ovarian steroid cell tumor with ectopic ACTH production. To our knowledge, it is the first reported case of ACTH secreting ovarian steroid cell tumor causing Cushing's syndrome.

Clinical and histopathological evaluation of the adrenal incidentaloma.

Clinically silent adrenal masses (incidentaloma) are incidentally discovered lesions, when noninvasive imaging methods (USG, CT, MRI) are performed for reasons other than known or suspected adrenal disease. Most studies report on a prevalence of adrenal incidentaloma range between 1% and 10% in radiological series. Between 1994 and 1999 we observed in our Department 57 patients with incidentalomas of adrenal glands. After endocrinological evaluation silent Cushing's syndrome was found in 2 cases (3.5%). Fifty two patients were qualified for surgery. Adrenocortical adenoma was diagnosed in 73.1%; adrenocortical carcinoma in 7.7%; pheochromocytoma in 7.7% and less frequent adrenal lesions in 11.5%. All adrenal carcinomas and malignant pheochromocytomas (11.5%) were found in tumors with diameter over 4 cm.

[Diagnostic difficulties in primary hyperparathyroidism based on personal observations]. / Trudnosci diagnostyczne pierwotnej nadczynnosci przytarczyc na podstawie obserwacji wlasnych.

The primary hyperparathyroidism (PHP) is a complex of nosological symptoms associated with disturbances of calcium-phosphate equilibrium and bone metabolism, caused by excessive secretion of parathormone. In the past regarded as a rare entity, today it is arousing great interest due to ever more frequent diagnosis of it in the stage of subtle changes or in the asymptomatic period. Untreated PHP leads to the development of a number of organ complications, and even to a life-threatening state, that is hypercalcemic crisis. The authors discussed differential diagnostic and localisation difficulties in PHP on example of own observations.

[A case of Kearns-Sayre syndrome]. / Przypadek zespolu Kaerns-Sayre.

In the literature there are only 3 cases of women with Kaerns-Sayre Syndrome (KSS) who delivered a healthy child. Our case is the fourth. The purpose of the report is to describe a 30-year old woman presenting typical clinical features of KSS, namely progressive external ophthalmoplegia, pigmentary retinal degeneration and onset of the disease before the age of 20. It was also associated with cardiac conduction defects, neurological symptoms and variety of endocrine and metabolic disorders. On muscle biopsy (m. biceps brachii) mitochondrial abnormalities on electron microscopy were seen. KSS is a form of mitochondrial myopathy with specific clinical features. Recognition of mtDNA deletion as the genetic basis of KSS confirmed the validity of clinical criteria.

[Complete heart block treated with electrotherapy in a 30-year-old pregnant women with Kearns-Sayre syndrome]. / Blok calkowity serca wymagajacy elektroterapii u 30-letniej ciezarnej z zespolem Kearns-Sayre.

Kearns-Sayre syndrome (KSS) is a form of mitochondrial myopathy in which specific clinical features, namely progressive external ophthalmoplegia, pigmentary retinal degeneration and onset before age 20 occur. It can also be associated with cardiac conduction defects, neurological and variety of endocrine and metabolic disorders. Recognition of mtDNA deletion as the genetic basis of KSS has confirmed the validity of clinical criteria. The purpose of the report is to describe a 30-year-old woman presenting typical clinical features of KSS. On muscle biopsy ragged red fibres and mitochondrial abnormalities on electron microscopy were seen. In spite of menstrual disturbances she became pregnant and delivered health child. In 30 week of pregnancy the VVI pacemaker was implanted because of syncope most probably related to paroxysmal complete heart block.

[Primary hyperparathyroidism--advances in diagnosis and treatment]. / Pierwotna nadczynnos'c' przytarczyc--poste,py w rozpoznawaniu i leczeniu.

The primary hyperparathyroidism (PHP) is a complex of nosological symptoms associated with disturbances of calcium-phosphate equilibrium and bone metabolism, caused by excessive secretion of parathyroid hormone. In the past regarded as rare entity, today it is arousing great interest due to ever more frequent diagnosis of it in the stage of subtle psychoneurological changes or in the asymptomatic period. Untreated PHP leads to the development of a number of organ complications, and even to a life-threatening state, that is hypercalcemic crisis. Surgical operation is the treatment of choice.