Diagnosis and treatment of neuroendocrine tumors - A series of 13 clinical cases (2014-2017).

Paragangliomas and pheocromocytomas are rare neuroendocrine tumors with different clinical presentation, being responsible for secondary arterial hypertension with target-organ lesions. Surgery is a curative therapy in these tumors and demands a multidisciplinary approach. These tumors are more frequent between the 4th and 5th decades of life and their clinical manifestations are related to catecholamines production: headache, palpitations, variable blood pressure. This article presents 13 clinical cases of patients with neuroendocrine tumors, with an median-age of 56,7 years, submitted to surgery between 2014 and 2017. The diagnosis was made based on clinical suspicion, serum and urinary catecholamines and metanephrins, imagiologic evaluation with CT or abdominal and pelvic MRI and MIBG scintigraphy. After surgery, the majority of patients remained with normal blood pressure, without anti-hypertensive therapy and follow-up was maintained in Outpatient Clinic, with periodic blood tests and imaging reevaluation.

On the influence of time-series length in EMD to extract frequency content: simulations and models in biomedical signals.

In this paper, fractional Gaussian noise (fGn) was used to simulate a homogeneously spreading broadband signal without any dominant frequency band, and to perform a simulation study about the influence of time-series length in the number of intrinsic mode functions (IMFs) obtained after empirical mode decomposition (EMD). In this context three models are presented. The first two models depend on the Hurst exponent H, and the last one is designed for small data lengths, in which the number of IMFs after EMD is obtained based on the regularity of the signal, and depends on an index measure of regularity. These models contribute to a better understanding of the EMD decomposition through the evaluation of its performance in fGn signals. Since an analytical formulation to evaluate the EMD performance is not available, using well-known signals allows for a better insight into the process. The last model presented is meant for application to real data. Its purpose is to predict, in function of the regularity signal, the time-series length that should be used when one wants to divide the spectrum into a pre-determined number of modes, corresponding to different frequency bands, using EMD. This is the case, e.g., in heart rate and blood pressure signals, used to assess sympathovagal balance in the central nervous system.

Abnormal myocardial flow reserve in sickle cell disease: a myocardial contrast echocardiography study.

BACKGROUND: Sickle cell disease (SCD) is characterized by obstruction of microvessels leading to ischemia and necrosis. We have aimed to demonstrate whether myocardial contrast echocardiography (MCE) is able to detect myocardial perfusion abnormalities in SCD patients and to assess their relationship with left ventricle (LV) perfusion and systolic function. METHODS: A group of 25 patients with SCD and a control group of 19 normal individuals were studied. Using MCE, myocardial perfusion reserve indices (A, beta, and A x beta) were obtained, before and after hyperemia with dypiridamole. LV function was also analyzed: ejection fraction (EF), index of myocardial performance (IMP), the ratio of transmitral early-diastolic flow velocity E and the pulsed tissue Doppler mitral annular early diastolic velocity Ea (E/Ea) (E/Ea), tissue Doppler mitral annular peak systolic velocity (Sa), and peak systolic strain (S) were obtained. RESULTS: Myocardial velocity (beta) and myocardial blood flow (A x beta) reserves were lower in the patients than in controls (1.7 +/- 0.4 vs. 3.3 +/- 0.2, P = 0.000 and 2.1 +/- 0.6 vs. 4.1 +/- 0.2, P = 0.000, respectively). In SCD patients, a correlation was found between beta reserve and EF, IMP, Sa, E/Ea, and S% and between A x beta reserve and Sa. CONCLUSIONS: MCE detected abnormal perfusion reserve in patients with SCD, which correlated with systolic function indices. This suggests that perfusion plays a role in SCD ventricular dysfunction.

Early modification of sickle cell disease clinical course by UDP-glucuronosyltransferase 1A1 gene promoter polymorphism.

Elevated erythrocyte destruction in sickle cell disease (SCD) results in chronic hyperbilirubinaemia and, in a subset of patients, cholelithiasis occurs. We investigated whether the (TA)n promoter polymorphism in the UDP-glucuronosyltransferase 1A1 gene (UGT1A1) may modify bilirubin metabolism, influencing bilirubinaemia, predisposition to cholelithiasis and subsequent cholecystectomy, in a group of 153 young SCD patients (mean age 12.0 +/- 9.0 years) predominantly of Bantu beta S haplotype. The concomitant effect of alpha thalassaemia was also analysed. Among the several UGT1A1 genotypes found, the most frequent were the (TA)6/(TA)6 (n = 37), (TA)6/(TA)7 (n = 60) and (TA)7/(TA)7 (n = 29). These groups of patients did not significantly differ in age, gender ratio and haemoglobin, foetal haemoglobin and reticulocyte levels. On the other hand, total bilirubin levels were significantly different between groups, with an increased (TA) repeat number being associated with higher bilirubinaemia. Furthermore, both cholelithiasis and cholecystectomy were more frequent in groups with higher (TA) repeat number, although the former association was not statistically significant. None of the mentioned parameters is statistically different within UGT1A1 groups with the presence of alpha thalassaemia. Thus, the UGT1A1 promoter polymorphism may represent an important nonglobin genetic modifier of Bantu SCD patients' clinical manifestations, even at a young age.

Wavelet analysis of autonomic outflow of normal subjects on head-up tilt, cold pressor test, Valsalva manoeuvre and deep breathing.

Non-invasive autonomic evaluation has used fast Fourier transform (FFT) to assign a range of low (LF) and high frequencies (HF) as markers of sympathetic and parasympathetic influences, respectively. However, FFT cannot be applied to brief transient phenomena, such as those observed on performing autonomic tests where the acute changes of cardiovascular signals (blood pressure and heart rate) that represent the first and most important stage of the autonomic performance towards a new state of equilibrium occur. Wavelet analysis has been proposed as a method to overcome and complement information taken exclusively in the frequency domain. With discrete wavelet transform (DWT), a time-frequency analysis can be done, allowing the visualization in time of the contribution of LF and HF to the observed changes of a particular signal. In this study, we evaluate with wavelets the acute changes in R-R intervals and systolic blood pressure that are observed in normal subjects during four classical autonomic tests: head-up tilt (HUT), cold pressor test (CPT), deep breathing (DB) and Valsalva manoeuvre (VM). Continuous monitoring of ECG and blood presure was performed. Also LF, HF and LF/HF were calculated. Consistent with previous interpretations, data showed an increase of sympathetic activity in HUT, CPT and VM. On DB, results reflected an increase in parasympathetic activity and frequencies. In conclusion, when compared with FFT, wavelet analysis allows the evaluation of autonomic variability during short and non-stationary periods of time and may constitute a useful advance in the assessment of autonomic function in both physiological and pathological conditions.

Tachycardiomyopathies.

Heart failure is a common disease with major social and economic repercussions for the health system. All potentially curable or reversible causes of heart failure should be investigated and treated if possible. Several experimental and clinical studies have demonstrated that supraventricular tachycardias can induce a form of dilated cardiomyopathy (tachycardiomyopathy), which may be reversible with ventricular frequency response control. In this article we present a clinical case, and review this clinical entity, so often underdiagnosed.

New transthyretin mutation V28M in a Portuguese kindred with amyloid polyneuropathy.

A 62-year-old Portuguese man, with no history of familial amyloid polyneuropathy (FAP), and a 2(1/2)-year history of tingling in the toes and sexual dysfunction was found neurophysiologically to have a sensory-motor axonal polyneuropathy. Autonomic tests showed slight sympathetic and marked parasympathetic involvement. Heart, kidney, and eyes were normal. Single strand conformation polymorphism (SSCP) mutation analysis for the transthyretin (TTR) gene was performed. The SSCP pattern suggested the presence of a mutation in exon 2, but was different from the pattern observed for a control representing the most common TTR mutation associated with FAP, i.e., TTR V30M. DNA sequencing analysis revealed an A-to-G transition in the first base of codon 28 normally encoding a valine, giving rise to a methionine residue. The presence of this extra methionine was confirmed by peptide mapping and mass spectrometry analysis. Biopsy of nerve and skin of the propositus showed amyloid deposits that were immunoreactive for TTR. This is a new variant TTR related to late-onset amyloid neuropathy with autonomic dysfunction. This case confirms that TTR mutation screening should be considered in patients with a clinical disorder consistent with amyloid neuropathy even in the absence of a family history.

[Atypical radiologic features of pulmonary tuberculosis. Nodular images in strings of balloons]. / Expressão Radiológica Atípica de Tuberculose Pulmonar. Imagens nodulares em largada de balões.

Chest radiographs are an important tool for the diagnosis and follow-up. Yet the radiographic findings can vary significantly, ranging from the so-called usual to unusual patterns. In this paper the authors report three cases of pulmonary tuberculosis in which the chest radiographs showed a nodular, pseudo-tumoral pattern. Based on literature and on their own experience, the authors discuss the frequency of this radiologic presentation in this setting and its correlation with the immunological status of the patient, the pathogenicity of Mycobacterium tuberculosis and the clinical presentation of the disease.

[Orthostatic tachycardia syndromes]. / Síndromes de taquicardia ortostática.

Orthostatic tachycardia may be due to several physiologic abnormalities. Normal regulation of cardiac frequency in relation to postural changes is described; main causes of orthostatic tachycardia are described, in particular hypovolemia, beta-adrenergic hypersensitivity and segmental autonomic neuropathy. The current therapeutic attitudes are discussed.

Streptococcus bovis spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.

Spontaneous bacterial peritonitis (SBP) is a frequent cause of decompensated alcoholic cirrhosis. The authors describe the first two cases caused by infection with Streptococcus bovis. They suggest that this microorganism may be present in the intestinal flora of these patients more frequently than assumed. Furthermore, the course of SBP due to S. bovis may be particularly severe.

[Assessment of cardiovascular reflexes in patients with mitral valve prolapse syndrome]. / Avaliação de reflexos cardiovasculares em doentes com síndrome do prolapso da válvula mitral.

OBJECTIVE: Functional evaluation of Autonomic Nervous System in patients with Mitral Valve Prolapse Syndrome. DESIGN: Study of cardiovascular reflexes. SETTING: Out patients studied in the Laboratory for Study of Autonomic Nervous System Function of Santa Maria Hospital, Lisbon, Portugal. MATERIAL AND METHODS: We studied 20 patients with clinical and echocardiographic diagnosis of mitral valve prolapse, who presented Mitral Valve Prolapse Syndrome, without significant mitral regurgitation, and with normal left ventricular function. Cardiovascular reflexes were analysed by mean of five tests. RESULTS: In 75% of the cases, patients had results according to vagal hypofunction. Orthostatic hypotension was present in 40%. Among patients with orthostatic hypotension, 75% had postural phenomena. Among patients with postural phenomena, 75% had orthostatic hypotension. CONCLUSIONS: In the present study, patients behaviour hasn't been uniform. Vagal hypofunction was present in 75% and orthostatic hypotension in 40% of the cases. A relation has been found between orthostatic hypotension and postural into.

Correlation between clinical, electromyographic and dysautonomic evolution of familial amyloidotic polyneuropathy of the Portuguese type.

To assess the correlation between the severity of clinical symptoms and sensorymotor and autonomic function in familial amyloidotic polyneuropathy of the Portuguese type (FAP-PT), clinical grade (CG), electromyographic score (ES), sympathetic (SS) and parasympathetic score (PS) were compared in 47 patients. SS and PS were both abnormal in 72% of patients with ES = 0% and in 73% of patients with CG = 0. When SS and PS were compared with either CG and ES, PS progressed more rapidly and stabilized earlier than SS. As a whole, SS and PS were greater as CG and ES were higher. This pattern of autonomic involvement should be taken into account when assessing the course of the disease and evaluating new forms of therapy.

Cerebrospinal fluid and therapy of isolated angiitis of the central nervous system.

BACKGROUND: Serial cerebral angiograms, computed tomography, and magnetic resonance imaging are among the proposed methods for monitoring disease activity and response to therapy in isolated angiitis of the central nervous system. Cerebrospinal fluid has not proved to be useful in monitoring clinical course. CASE DESCRIPTION: We describe a 45-year-old man with histological diagnosis of isolated angiitis of the central nervous system that was treated with prednisone plus azathioprine and monitored for 2 years. Samples of the cerebrospinal fluid were obtained for cytological and routine chemical examination, as well as albumin and immunoglobulin content. Before treatment, cerebrospinal fluid showed marked plasmatic transudation of albumin and intrathecal synthesis of immunoglobulins. During the first year of immunosuppression no events were noticed, and the previously abnormal aspects of the cerebrospinal fluid showed improvement. During the weaning of azathioprine, a new stroke occurred in conjunction with a marked deterioration of cerebrospinal fluid parameters. Immunosuppression was resumed at previous levels, and during the following year no further events occurred. Once again, abnormal cerebrospinal fluid values improved significantly. CONCLUSIONS: We report a case of isolated angiitis of the central nervous system in which the serial cerebrospinal fluid examinations (albumin and immunoglobulin content) showed a close correlation with clinical course. This method may be useful in monitoring response to therapy.

[Pure autonomic failure]. / Falência autonómica pura.

We present the case of a 64-year-old woman who, in the past 5 years, complained of constipation/diarrhea, hyposudoresis, xerostomia and xerophthalmia, dysuria and orthostatic hypotension. Cardiovascular reflexes analysis revealed sympathetic and parasympathetic failure. Norepinephrine was markedly reduced, both lying and after tilt. Norepinephrine infusion determined a significant rise in blood pressure, allowing the diagnosis of denervation hypersensitivity. The diagnosis of pure autonomic failure was made. Therapy with 9 alpha fludrocortisone and metoclopramide was initiated with marked and sustained symptomatic effect.

Composite tumor of the main bile duct producing several regulatory peptides.

Herein we describe what is, to our knowledge, the first reported case of a composite tumor of the main bile duct with epiploon metastases. Glucagon, pancreatic polypeptide, and somatostatin-immunoreactive cells were demonstrated in these metastases, but not serotonin, gastrin, or insulin-immunoreactive cells. The clinical significance of the neuroendocrine cells in the present case is discussed.

Plasma catecholamines and postural hypotension in familial amyloidotic polyneuropathy of the Portuguese type.

Plasma adrenaline and noradrenaline levels were measured while supine and following head-up tilt to 45 degrees, in both normal controls and in patients with familial amyloidotic polyneuropathy of the Portuguese type. In nine patients systolic blood pressure fell by less than 15 mmHg, while in seven patients it fell by more than 15 mmHg. Plasma noradrenaline rose during tilt in the majority of patients, as in the controls. There was no correlation between levels of catecholamines and fall in blood pressure on head-up tilt. The data excludes widespread sympatho-neural failure as a cause for postural hypotension in familial amyloidotic polyneuropathy of the Portuguese type. The results are compatible with either segmental/patchy sympathetic denervation or dysfunction of the receptor/effector mechanisms in target organs such as the heart and blood vessels.

A case of systemic mastocytosis; therapeutic efficacy of ketotifen.

A 68-year-old man presented with a 6-month history of fatigue, rhinorrhoea, pruritic skin lesions, left pleural effusion, ascites, oedema and weight loss of 10 kg. Investigations revealed hepatosplenomegaly, retroperitoneal lymphadenopathy, anaemia, leucocytosis with eosinophilia, hypoprothrombinaemia, hypocholesterolaemia and elevation of both gamma glutamyltransferase and alkaline phosphatase. Biopsies of a skin lesion, bone marrow and liver revealed mast cell infiltration, allowing the diagnosis of systemic mastocytosis (SM). Hydroxyzine plus ranitidine were given without success. Hydroxyzine treatment was stopped, and ketotifen was initiated; substantial symptomatic improvement was observed within 8 d. This case report indicates the effectiveness of ketotifen in the symptomatic treatment of SM.