Feocromocitoma y paraganglioma en un hospital pediátrico de Argentina. Serie de casos / Pheochromocytoma and paraganglioma at a children's hospital in Argentina. A case series

El feocromocitoma y el paraganglioma son tumores neuroendocrinos secretores de catecolaminas. Los feocromocitomas se originan en la médula suprarrenal, mientras que los paragangliomas son extraadrenales. Se describe una serie de casos de niños con diagnóstico anatomopatológico de feocromocitoma o paraganglioma que consultaron en un hospital pediátrico de alta complejidad de Argentina. Se incluyeron 21 pacientes, 14 varones, con una mediana de edad de 11,4 años; 8 casos con feocromocitoma y 13 casos con paraganglioma. Se presentaron con hipertensión arterial 14/21. La mayoría de los paragangliomas tuvieron localización paraaórtica (9/13). Debido a que representan una causa potencialmente curable de hipertensión arterial, la sospecha clínica es muy importante. El diagnóstico temprano y la instauración de un tratamiento antihipertensivo adecuado, que permita afrontar la cirugía con normotensión arterial, aseguran la curación en la mayoría de los casos si la resección tumoral es completa.

Pheochromocytomas and paragangliomas are neuroendocrine tumors producing catecholamines. Pheochromocytomas occur in the adrenal medulla, while paragangliomas are those that occur outside the adrenal gland. Here we describe a case series of children with a pathological diagnosis of pheochromocytoma or paraganglioma who consulted at a tertiary care children's hospital in Argentina. A total of 21 patients (14 males) were included; their median age was 11.4 years; 8 children had pheochromocytoma and 13, paraganglioma. Arterial hypertension was observed in 14/21. Most paragangliomas were para-aortic (9/13). Since they are a potentially curable cause of hypertension, clinical suspicion is very important. An early diagnosis and the initiation of an adequate antihypertensive treatment, which allows the patient to undergo surgery with normal blood pressure, ensure a cure in most cases if tumor resection is complete.

Hallazgo casual de un paraganglioma paraaórtico / An incidentally discovered paraaortic paraganglioma

Introducción: los paragangliomas son tumores neuroendocrinos derivados de células cromafi nes. Son entidadesmuy infrecuentes que se localizan típicamente en el cuello o en la base del cráneo. presentamos el caso de unparaganglioma paraaórtico, una ubicación inusual que cuenta con escasos reportes en la literatura. Caso clínico: mujer de 78 años que presenta una masa retroperitoneal hallada de forma casual durante el estudiopreoperatorio de una neoplasia ginecológica. ante la sospecha de un tumor del estroma gastrointestinal o unschawnnoma retroperitoneal, se indica su extirpación quirúrgica. Durante la operación se objetiva una masa muyvascularizada adherida a la cara anterior de la aorta, cuya resección provoca en la paciente un cuadro de crisishipertensiva y taquicardia asociadas a inestabilidad hemodinámica, que cede tras completar su exéresis. el estudioanatomopatológico posterior confi rma la sospecha diagnóstica intraoperatoria de paraganglioma paraaórtico. Discusión: los paragangliomas localizados en el abdomen suelen ser productores de catecolaminas y puedendesarrollar clínica adrenérgica de forma espontánea o inducida por fármacos, ejercicio o manipulación quirúrgica,como sucedió en nuestro caso. Un diagnóstico certero es clave para planificar un tratamiento adecuado quepermita reducir las posibles complicaciones en este tipo de pacientes.(AU)

Introduction: paragangliomas are neuroendocrine tumours derived from chromaffin cells. they are very rareentities that are typically located in the neck or at the base of the skull. We present the case of a para-aortic para-ganglioma, an unusual location that has few reports in the literature. Case report: a 78-year-old woman with a retroperitoneal mass found incidentally during the preoperative study fora gynecological neoplasm. Given the suspicion of a gastrointestinal stromal tumour or a retroperitoneal schawn-noma, surgical removal of it was indicated. Intraoperatively, a highly vascularized mass adhered to the anteriorface of the aorta was observed, whose resection caused a hypertensive crisis and tachycardia associated withhemodynamic instability, which subsided after completing the exeresis. the subsequent anatomopathologicalstudy confirmed the intraoperative diagnostic suspicion of paraaortic paraganglioma. Discussion: paragangliomas located in the abdomen are usually catecholamine producers and can develop adr-energic symptoms spontaneously or induced by drugs, exercise, or surgical manipulation, as occurred in our case.an accurate diagnosis is the key to planning an appropriate treatment that allows reducing possible complicationsin this type of patient.(au)

Antiplatelet therapy at discharge and long-term prognosis in Takotsubo syndrome: Insights from the Spanish National Registry (RETAKO).

INTRODUCTION: Endothelial dysfunction and platelet activation have been highlighted as possible mediators in Takotsubo syndrome (TTS). Nevertheless, to date, evidence on the usefulness of antiplatelet therapy in TTS remains controversial. The aim of our study is to evaluate long-term prognosis in TTS patients treated with antiplatelet therapy (APT) at hospitalization discharge. MATERIAL AND METHODS: An ambispective cohort study from the Spanish National Takotsubo Registry database was performed (June 2002 to March 2017). Patients were divided into two groups: those who received APT at hospital discharge (APT cohort) and those who did not (non-APT cohort). Primary endpoint was all-cause death. Secondary endpoints included the composite of recurrence or readmission and a composite of death, recurrence or readmission. RESULTS: From a total of 741 patients, 728 patients were alive at discharge. Follow-up was performed in 544 patients, who were included in the final analysis: 321 patients (59.0%) in the APT cohort and 223 patients (41.0%) in the non-APT cohort. The APT cohort had a better clinical presentation and received more heart failure and acute coronary syndrome-like therapies (angiotensin converting enzyme inhibitors/angiotensin receptor blockers: 75.1% vs. 51.1%; p<0.001, betablockers: 71.3% vs. 50.7%; p<0.001, statins: 67.9% vs. 33.2%; p<0.001). After adjusting for confounder factors, APT at discharge was a protective factor for all-cause death (adjusted hazard ratio (HR) 0.315, 95% confidence interval (CI): 0.106-0.943; p=0.039) and the composite endpoint of all-cause death, recurrence or readmission (adjusted HR 0.318, 95% CI: 0.164-0.619; p=0.001) at month 25 of follow-up. CONCLUSION: Patients with TTS receiving APT at discharge presented better prognosis up to two-years of follow-up compared with their counterparts not receiving APT.

Síndrome coronario agudo por feocromocitoma

RESUMEN El feocromocitoma es un tumor cromafín ubicado generalmente en la glándula suprarrenal, originado en células del neuroectodermo y productor de catecolaminas. Se presenta caso clínico de varón de 56 años con antecedente de hipertensión arterial que consultó por síntomas de un síndrome coronario agudo. La cinecoronariografía descarta cardiopatía isquémica ateroesclerótica y se llegó al diagnóstico de feocromocitoma a partir de los estudios de imágenes y la anatomía patológica. El tumor fue extirpado con cirugía abierta. En la hipertensión arterial de difícil manejo y en patologías cardiacas de presentaciones atípicas, el feocromocitoma debe ser tenido en cuenta como diagnóstico diferencial.

ABSTRACT Pheochromocytoma is a chromaffin tumor generally located in the adrenal gland, originated in neuroectoderm cells and a catecholamine-producing tumor. We present a clinical case of a 56-year-old man with a history of arterial hypertension who consulted for symptoms of an acute coronary syndrome. The coronary angiography ruled out atherosclerotic ischemic heart disease and the diagnosis of pheochromocytoma was reached based on imaging studies and pathology. The tumor was removed with open surgery. In arterial hypertension that is difficult to manage and in cardiac pathologies with atypical presentations, pheochromocytoma must be taken into account as a differential diagnosis.

Feocromocitoma adrenal gigante derecho. Reporte de un caso / Right giant adrenal pheochromocytoma. A case report

Introducción. El feocromocitoma es una neoplasia endocrina productora de catecolaminas, poco común, que generalmente se origina en la medula suprarrenal, y rara vez en el tejido cromafín extraadrenal, dándosele el nombre de paraganglioma. Existe una gran variedad de signos y síntomas secundarios a la secreción excesiva de catecolaminas por lo que su diagnóstico y tratamiento oportunos son fundamentales para evitar complicaciones potencialmente fatales. Caso clínico. Paciente femenina de 54 años, con dolor abdominal intermitente y con aumento progresivo, localizado en el cuadrante superior derecho. Por estudios imagenológicos se diagnosticó una gran masa suprarrenal derecha, con pruebas de laboratorio que encontraron niveles de metanefrinas y catecolaminas en orina normales. Discusión. Debido al tamaño del tumor y al íntimo contacto con las estructuras adyacentes, se realizó la resección por vía abierta, sin complicaciones y con una buena evolución postoperatoria. El informe anatomopatológico confirmó el diagnóstico de feocromocitoma suprarrenal derecho. Conclusión. Aunque poco frecuente, el feocromocitoma es una patología que se debe sospechar ante la presencia de masas suprarrenales y alteraciones relacionadas con la secreción elevada de catecolaminas. Se debe practicar el tratamiento quirúrgico de forma oportuna.

Introduction. Pheochromocytoma is a rare catecholamine-producing endocrine neoplasm that generally originates in the adrenal medulla, and rarely in extra-adrenal chromaffin tissue, giving it the name of paraganglioma. There is a wide variety of signs and symptoms secondary to excessive secretion of catecholamines, so its timely diagnosis and treatment are essential to avoid potentially fatal complications. Clinical case. A 54-year-old female patient with intermittent abdominal pain and progressive increase, located in the right upper quadrant. By imaging studies, a large right adrenal mass was diagnosed, with laboratory tests that found normal levels of metanephrines and catecholamines in urine. Discussion. Due to the size of the tumor and the intimate contact with the adjacent structures, the resection was performed by open approach, without complications and with a good postoperative evolution. The pathology report confirmed the diagnosis of right adrenal pheochromocytoma. Conclusion. Although rare, pheochromocytoma is a pathology that should be suspected in the presence of adrenal masses and changes related to elevated catecholamine secretion. Surgical treatment should be performed in a timely manner.

Anaesthetic management of a dopamine-secreting phaeochromocytoma.

Pheochromocytomas are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla. Most adrenal pheochromocytomas secrete norepinephrine and epinephrine. Dopamine secreting pheochromocytomas are extremely rare and differs from classic pheochromocytomas in clinical features, posing a significant diagnostic challenge. A 41-year-old women presented to our emergency department because of acute flank colic pain and normotension. The screening abdominal computed tomography scan revealed a left adrenal mass. The laboratory test showed significantly increase in plasma dopamine and 24-h urine dopamine. During surgical removal the patient remained hypotensive requiring doses of norepinephrine. The patient presented significant hypertensive responde during direct laryngoscopy and intubation.

Manejo anestésico de feocromocitoma productor de dopamina / Anaesthetic management of a dopamine-secreting phaeochromocytoma

El feocromocitoma es un tumor neuroendocrino raro que se origina en las células cromafines de la cresta neural del sistema nervioso autónomo. La mayoría de las feocromocitomas se caracterizan por secretar adrenalina y noradrenalina. Los productores de dopamina son infrecuentes y no presentan la sintomatología clínica típica, por lo que el diagnóstico puede ser complicado. Actualmente disponemos de escasa bibliografía sobre el manejo anestésico de este tipo de tumores.Presentamos el caso clínico de una mujer de 41 años que acudió a nuestro centro por dolor lumbar de tipo cólico de un mes de evolución y normotensión. Se realizó una tomografía axial computarizada abdominal que reveló masa hipercaptante en glándula suprarrenal izquierda. Los niveles de dopamina en orina y en plasma estaban elevados, los niveles de adrenalina y noradrenalina eran normales. Durante la intervención quirúrgica la paciente se mantuvo hipotensa precisando dosis de noradrenalina. Solo presentó un único pico hipertensivo durante la laringoscopia y la intubación orotraqueal.(AU)

Pheochromocytomas are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla. Most adrenal pheochromocytomas secrete norepinephrine and epinephrine. Dopamine secreting pheochromocytomas are extremely rare and differs from classic pheochromocytomas in clinical features, posing a significant diagnostic challenge.A 41-year-old women presented to our emergency department because of acute flank colic pain and normotension. The screening abdominal computed tomography scan revealed a left adrenal mass. The laboratory test showed significantly increase in plasma dopamine and 24-hour urine dopamine. During surgical removal the patient remained hypotensive requiring doses of norepinephrine. The patient presented significant hypertensive responde during direct laryngoscopy and intubation.(AU)

Vasopressin as rescue therapy in pediatric catecholamine-refractory shock / Vasopressina como terapia de resgate em choque refratário à catecolamina em crianças

Introduction: There is scarce evidence on the efficacy of vasopressin as a vasopressor agent in pediatric catecholamine-refractory shock. The aim of this study is to describe hemodynamic changes during the first hours of administration vasopressin as rescue therapy in patients with catecholamine-refractory shock. Methods: This is a retrospective study including children from 1 month to 18 years admitted to the PICU who received vasopressin as rescue therapy for catecholamine-refractory shock (noradrenalin ≥1µg/ kg/min and variable doses of other inotropic / vasopressor agents). For analysis purposes, blood pressure means and modified vasoactive scores were calculated at two time periods: 2 hours prior to vasopressin therapy (T-2) and within the first 10 hours of vasopressin therapy (T10). Results: Using the paired Students' t test, mean blood pressure and vasoactive-inotropic scores modified by Wernovsky in the 2 hours before the use of vasopressin (T-2) were compared with the means of the first 10 hours of vasopressin administration (T10). The sample consisted of 16 patients. Median initial dose of vasopressin was 0.0005U/kg/min (interquartile range 0.00024-0.00168). Mean blood pressure and diastolic blood pressure increased with the use of vasopressin (p=0.0267 and p=0.0194, respectively). There was no reduction in vasoactive-inotropic score or increased diuresis. Conclusion: The administration of vasopressin increased blood pressure in this sample but did not promote a reduction in catecholamine scores nor increased diuresis.

Introdução: Há escassez de evidências sobre a eficácia da vasopressina como agente vasopressor no choque refratário à catecolamina em crianças. O objetivo foi descrever as alterações hemodinâmicas que ocorrem nas primeiras horas de administração da vasopressina, como terapia de resgate em pacientes com choque refratário à catecolamina. Métodos: Estudo retrospectivo. Foram incluídas crianças de 1 mês a 18 anos internadas na UTIP que receberam vasopressina como terapia de resgate para choque refratário à catecolamina (noradrenalina ≥1µg/kg/min e doses variáveis de outros inotrópicos /vasopressores). Para fins de análise, as medidas da pressão arterial e os escores vasoativos modificados foram calculados em dois períodos: nas 2 horas anteriores ao início da terapia com vasopressina (T-2) e nas primeiras 10 horas da terapia com vasopressina (T10). Resultados: Utilizando o teste t de Student pareado, a pressão arterial média e o escore vasoativo-inotrópico modificado por Wernovsky nas 2 horas anteriores ao uso de vasopressina (T-2) foram comparados com as médias dessas variáveis durante as primeiras 10 horas de administração de vasopressina (T10). A amostra foi composta por 16 pacientes. A dose mediana inicial de vasopressina foi de 0,0005U/kg/min (intervalo interquartil 0,00024-0,00168). A pressão arterial média e a pressão arterial diastólica aumentaram com o uso de vasopressina (p=0,0267 e p=0,0194, respectivamente). Não houve redução no escore vasoativo-inotrópico ou aumento na diurese. Conclusão: A administração de vasopressina aumentou a pressão arterial nesta amostra, mas não teve efeitos na redução dos escores de catecolaminas ou no aumento da diurese.

Lactato y catecolaminas: respuesta fisiológica en el paciente crítico / Lactate and catecholamines: a physiological response in critically ill patients

RESUMEN El lactato es un metabolito altamente dinámico que, en condiciones anaerobias, es producido por hipoxia o isquemia; y en condiciones aerobias, es sintetizado por un mecanismo impulsado por la estimulación adrenérgica, a través del receptor β2, que potencia la acción de la bomba sodio-potasio, y por un estado de glicólisis aerobia acelerada. Este metabolito es capaz de intercambiarse entre diferentes células productoras y consumidoras, con lo que asegura la materia prima para obtener energía. El sistema nervioso simpático responde a los estímulos de estrés con la liberación de catecolaminas, que actúan como hormonas y como neurotransmisores en varios tejidos del cuerpo y permiten un aumento del metabolismo que eleva los valores de glucosa y el oxígeno disponible. Existe una relación fisiológica de dependencia entre las catecolaminas y la producción de lactato que predispone al organismo para responder de forma efectiva ante una situación de estrés. Sin embargo, en tejidos sensibles, la respuesta adrenérgica exacerbada puede ocasionar efectos exagerados que pueden incrementar la probabilidad de fallo. En base al conocimiento de estos mecanismos, se plantean estrategias terapéuticas enfocadas en regular la actividad simpática.

ABSTRACT Lactate is a highly dynamic metabolite that is produced, under anaerobic conditions, due to hypoxia or ischemia. Under aerobic conditions, it is synthesized by a mechanism driven by the stimulation of the β2 adrenergic receptor, which increases the activity of the sodium-potassium pump, and by a state of accelerated aerobic glycolysis. This metabolite is capable of being exchanged between different producing and consuming cells, ensuring the raw material for energy production. The sympathetic nervous system responds to stress stimuli through the release of catecholamines, which act as hormones and neurotransmitters in various tissues of the body, allowing an increase in metabolism that raises glucose and available oxygen levels. There is a physiological dependence between catecholamine levels and lactate production, predisposing the body to respond effectively to a stressful situation. However, an exacerbated adrenergic response may cause exaggerated effects on sensitive tissues that increase the probability of failure. Based on the knowledge of these mechanisms, therapeutic strategies focused on regulating the sympathetic activity are proposed.

Dysregulation in the secretion of the stress-related catecholamines in oral cancer patients: predictors and prognostic value / Desregulação da secreção das catecolaminas relacionadas ao estresse em pacientes com câncer de boca: valor preditivo e prognóstico

Introdução: Pacientes com câncer podem apresentar uma hiperativação do Sistema Nervoso Simpático (SNS). Como consequência, uma desregulação na secreção das catecolaminas relacionadas ao estresse norepinefrina (NE) e epinefrina (EPI) têm sido implicadas na progressão de alguns tipos de tumores malignos. No entanto, a associação entre os níveis sistêmicos das catecolaminas e o prognóstico do câncer, bem como seus fatores preditores são pobremente conhecidos. Pacientes e métodos: O presente estudo investigou os níveis plasmáticos de NE e EPI em 168 pacientes com carcinoma espinocelular (CEC) de boca, 70 pacientes com leucoplasia bucal e 54 voluntários saudáveis; bem como sua associação com variáveis demográficas, clínicopatológicas, biocomportamentais e psicológicas nos pacientes oncológicos. Os níveis plasmáticos de NE e EPI foram medidos por cromatografia líquida de alta eficiência com detecção eletroquímica (CLAE-ED) e o estado psicológico de humor foi avaliado pela Escala de Humor de Brunel (BRUMS). Análise de Kaplan-Meier e regressão de Cox foram usadas para investigar as associações entre os níveis de NE e EPI e a sobrevida global e específica após 5 anos de follow-up em 82 pacientes com câncer de boca. Os níveis sistêmicos das catecolaminas também foram avaliados em 32 pacientes após o tratamento da doença e comparados com os níveis pré-tratamento. Resultados: As concentrações plasmáticas de NE e EPI foram significativamente maiores em pacientes com CEC de boca em comparação aos pacientes com leucoplasia bucal (p< 0,0001 e p=0,024, respectivamente). Os pacientes com CEC de boca também apresentaram níveis plasmáticos de NE mais elevados do que os voluntários saudáveis (p= 0,0002). As concentrações plasmáticas de NE nos pacientes com leucoplasia bucal foram menores do que os voluntários saudáveis (p= 0,032). Análises de regressão múltipla mostraram que níveis aumentados de NE foram significativamente associados com uma sensação de "sentir-se sem energia", um descritor medido pelo BRUMS (OR= 2,9; p= 0,023). Baixa escolaridade e ocorrência de comorbidades com maior severidade foram independentemente associados a altos níveis de EPI (OR= 4,0; p= 0,004 e OR= 7,2; p= 0,005; respectivamente). Além disso, a presença de um estado de humor de raiva e "não estar em alerta" foram associados a altos níveis plasmáticos de EPI (OR= 2,6; p= 0,039 e OR= 3,2; p= 0,010, respectivamente). Os resultados mostraram que os pacientes com CEC de boca não casados e que tinham pior renda familiar foram preditivos para menor sobrevida global dos pacientes com CEC de boca (p< 0,05). Estágio clínico avançado foi associado à diminuição da sobrevida global (HR= 5,2; p= 0,000) e específica do câncer (HR= 4,2; p= 0,000). A análise de regressão de Cox também evidenciou que níveis sistêmicos aumentados tanto de NE como de EPI foram associados à menor sobrevida global (HR= 3,4; p= 0,002 e HR= 2,8; p=0,006, respectivamente). Os pacientes com CEC de boca apresentaram níveis plasmático de NE mais baixos após o tratamento do câncer em comparação com a fase pré-tratamento (p= 0,0008). Conclusão: Os resultados do presente estudo mostram que pacientes com câncer de boca podem apresentar níveis sistêmicos elevados das catecolaminas norepinefrina e epinefrina, e que esta desregulação hormonal associada com fatores clinicopatológicos e psicológicos é preditiva para pior sobrevida global(AU)

Introduction: Cancer patients may have a hyperactivation of the Sympathetic Nervous System (SNS). Therefore, dysregulation in the secretion of the stress-related catecholamines norepinephrine (NE) and epinephrine (EPI) have been implicated in the progression of some types of cancer. However, the association between systemic levels of catecholamines and cancer prognosis, as well as its predictors, are poorly understood. Patients and methods: The present study investigated the plasma NE and EPI levels in 168 patients with oral squamous cell carcinoma (OSCC), 70 patients with oral leukoplakia and 54 healthy volunteers; as well as its association with demographic, clinicopathological, biobehavioral and psychological variables in cancer patients. Plasma NE and EPI levels were measured by high performance liquid chromatography with electrochemical detection (HPLC-ED) and psychological mood states was assessed by the Brunel Mood Scale (BRUMS). Kaplan-Meier analysis and Cox regression were used to investigate associations between the systemic levels of catecholamines and overall and specific survival after 5 years of follow-up in 82 patients with oral cancer. Systemic levels of catecholamines were also evaluated in 32 patients after oral cancer treatment and were compared with pre-treatment levels. Results: Plasma NE and EPI concentrations were significantly higher in patients with oral SCC compared to patients with oral leukoplakia (p<. 0001 and p=.024, respectively). Patients with oral SCC also displayed higher plasma NE levels than healthy volunteers (p=.0002). Patients with oral leukoplakia had lower plasma NE levels than healthy volunteers (p=.032). Multiple regression analyzes showed that increased NE levels were associated with a feeling of "no energy", a descriptor measured by BRUMS (OR= 2.9; p= .023). Low education and the occurrence of severe comorbidities were independently associated with high levels of EPI (OR= 4.0; p= .004 and OR= 7.2; p= .005; respectively). Furthermore, the presence of an angry mood state and denial of "being on alert" were associated with high EPI levels (OR= 2.6; p= .039 and OR= 3.2; p= .010, respectively). The results showed that nonmarried oral SCC patients and those who had a lower family income had lower overall survival in patients with oral SCC (p< 0.05). Advanced clinical stage was associated with decreased overall (HR=5.2; p=.000) and cancer-specific (HR=4.2; p=.000) survival. Cox regression analysis also showed that increased levels of both NE and EPI were associated with worse overall survival (HR=3.4; p=.002 and HR=2.8; p=.006, respectively). Patients with oral SCC had lower plasma NE levels after cancer treatment compared to the pre-treatment period (p=.0008). Conclusion: The results of the present study reveal that patients with oral cancer may have high systemic levels of the catecholamines norepinephrine and epinephrine, and that this hormonal dysregulation is associated with clinicopathological and psychological factors and predictive for worse overall survival(AU)

Catecholamines production by kidney tissue and mesangial cell culture is differentially modulated by diabetes / A produção de catecolaminas pelo tecido renal e a cultura de células mesangiais é modulada diferencialmente pelo diabetes

Abstract Introduction: According to the International Diabetes Federation, the number of people with diabetes mellitus may reach 700 million in 2045. Catecholamines are involved in the regulation of several kidney functions. This study investigates the effects of hyperglycemia on catecholamines' metabolism in kidney tissue from control, diabetic, and insulin-treated diabetic rats, both in vivo and in vitro. Methods: Male Wistar-Hannover rats were randomized into: control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by a single injection of streptozotocin, and diabetic treated group also received insulin. After 60 days, blood and kidney tissue from all groups were collected for catecholamines' quantification and mesangial cells culture. Results: diabetic rats had lower body weight, hyperglycemia, and increase water intake and diuresis. Additionally, diabetes promoted a sharp decrease in creatinine clearance compared to control group. Regarding the whole kidney extracts, both diabetic groups (treated and non-treated) had significant reduction in norepinephrine concentration. In mesangial cell culture, catecholamines' concentration were lower in the culture medium than in the intracellular compartment for all groups. Norepinephrine, epinephrine, and dopamine medium levels were increased in the diabetic group. Conclusion: The major finding of the present study was that 8 weeks of diabetes induction altered the kidney catecholaminergic system in a very specific manner, once the production of catecholamines in the excised kidney tissue from diabetic rats was differentially modulated as compared with the production and secretion by cultured mesangial cells.

Resumo Introdução: Segundo a Federação Internacional de Diabetes, o número de pessoas com diabetes mellitus pode chegar a 700 milhões em 2045. As catecolaminas estão envolvidas na regulação de várias funções renais. Este estudo investiga os efeitos da hiperglicemia no metabolismo das catecolaminas no tecido renal de ratos controle, diabéticos e diabéticos tratados com insulina, tanto in vivo como in vitro. Métodos: Os ratos Wistar-Hannover machos foram randomizados em: grupos controle, diabéticos e diabéticos tratados com insulina. O diabetes foi induzido por uma única injeção de estreptozotocina, e o grupo diabético tratado também recebeu insulina. Após 60 dias, sangue e tecido renal dos grupos foram coletados para quantificação de catecolaminas e cultura de células mesangiais. Resultados: ratos diabéticos apresentaram peso corporal mais baixo, hiperglicemia, e aumento da ingestão de água e diurese. Ademais, o diabetes promoveu uma redução acentuada na depuração de creatinina comparado com o grupo controle. Quanto aos extratos de rim total, ambos os grupos diabéticos (tratados/não tratados) tiveram redução significativa na concentração de noradrenalina. Na cultura de células mesangiais, a concentração de catecolaminas foi menor no meio de cultura do que no compartimento intracelular para todos os grupos. Níveis médios de noradrenalina, adrenalina e dopamina estavam aumentados no grupo diabético. Conclusão: O principal achado deste estudo foi que 8 semanas de indução de diabetes alteraram o sistema catecolaminérgico renal de maneira muito específica, já que a produção de catecolaminas no tecido renal excisado de ratos diabéticos foi modulada diferencialmente comparada com produção e secreção por células mesangiais cultivadas.

Impacto cardiovascular, conducta diagnóstica y terapéutica del feocromocitoma como causa de hipertensión arterial / Cardiovascular impact, diagnostic and therapeutic management of pheochromocytoma as a cause of arterial hypertension

INTRODUCCIÓN. Los feocromocitomas son tumores que provienen de las células neuroendócrinas de la médula adrenal y producen alta secreción de catecolaminas. Generan complicaciones cardiovasculares graves que suelen asociarse con crisis hipertensivas. Es importante valorar el impacto cardiovascular de esta entidad. OBJETIVO. Realizar una revisión exhaustiva de las diversas manifestaciones de los feocromocitomas como causa de hipertensión arterial, su impacto cardiovascular, conducta diagnóstica y terapéutica. MATERIALES Y MÉTODOS. Revisión bibliográfica y análisis de 141 artículos científicos que incluyeron temas sobre el impacto cardiovascular, conducta diagnóstica y terapéutica del feocromocitoma como causa de hipertensión arterial. Se usó bases de datos: Medline, Embase, Scopus, Pubmed, Google Académico. Criterios de búsqueda en DECS, MeSH: "pheochromocytoma OR hypertension arterial AND cardiomyopathy", en inglés- español. Fueron seleccionados: 13 publicaciones de texto completo, 10 artículos retrospectivos, 2 guías de práctica clínica y 1 revisión. Se excluyeron 128 artículos científicos. RESULTADOS. Se realizó una revisión de las manifestaciones clínicas de los feocromocitomas como causa de hipertensión arterial y el impacto cardiovascular se relacionó con la producción de catecolaminas. Para el diagnóstico, la sensibilidad de la resonancia magnética es del 93-100%; la especificidad de resonancia magnética o tomografía computarizada en combinación con gammagrafía con metayodobencilguanidina con 123I es cercana al 100%. La resección del feocromocitoma tiene potencial curativo. CONCLUSIÓN. Los feocromocitomas presentan variabilidad clínica, se asocian a complicaciones cardiovasculares y cerebrovasculares graves por producción de catecolaminas. El diagnóstico oportuno y eficaz debe realizarse mediante resonancia magnética y gammagrafía en caso de alta sospecha clínica. El tratamiento quirúrgico es de elección.

INTRODUCTION. Pheochromocytomas are tumors arising from the neuroendocrine cells of the adrenal medulla and produce high secretion of catecholamines. They generate severe cardiovascular complications that are often associated with hypertensive crises. It is important to assess the cardiovascular impact of this entity. OBJECTIVE. To perform an exhaustive review of the various manifestations of pheochromocytomas as a cause of arterial hypertension, their cardiovascular impact, diagnostic and therapeutic conduct. MATERIALS AND METHODS. Bibliographic review and analysis of 141 scientific articles that included topics on the cardiovascular impact, diagnostic and therapeutic behavior of pheochromocytoma as a cause of arterial hypertension. The following databases were used: Medline, Embase, Scopus, Pubmed, Google Scholar. Search criteria in DECS, MeSH: "pheochromocytoma OR hypertension arterial AND cardiomyopathy", in English-Spanish. The following were selected: 13 full-text publications, 10 retrospective articles, 2 clinical practice guidelines, and 1 review. A total of 128 scientific articles were excluded. RESULTS. A review of the clinical manifestations of pheochromocytoma as a cause of arterial hypertension was performed and the cardiovascular impact was related to catecholamine production. For diagnosis, the sensitivity of MRI is 93-100%; the specificity of MRI or computed tomography in combination with 123I-methiodobenzylguanidine scintigraphy is close to 100%. Resection of pheochromocytoma has curative potential. CONCLUSION. Pheochromocytomas present clinical variability, are associated with severe cardiovascular and cerebrovascular complications due to catecholamine production. Timely and effective diagnosis should be made by MRI and scintigraphy in case of high clinical suspicion. Surgical treatment is the treatment of choice.

Paraganglioma neuroendocrine tumor and psychiatric implications. A case report / Tumores neuroendocrinos de tipo paraganglioma e implicaciones psiquiátricas: Caso clínico

Objective: Paragangliomas are rare neuroendocrine tumors. Occasionally they secrete catecholamines in sufficient quantities to cause symptoms. The majority of the cases, with the resection of the tumor, the psychotic symptoms disappeared and that is associated with the decreased levels of catecholamines. Clinical case: We report the case of 56-year-old women with residual schizophrenia who started with acute symptoms characterized by palpitations, dyspnea, headache and facial rubbing with no response to antihypertensive treatment. At the same time she suddenly had positive psychosis symptoms, after a long time with residual and negative symptoms. Conclusions: With the presentation of this case we want to highlight the signs that suggest the autonomic instability in psychosis patients, and how crucial is excluding underlying somatic conditions. We also examine the possible relationships between neural crest cell tumor that secrete catecholamines and schizophrenia. (AU)

Objetivo: Los paragangliomas son tumores neuroendocrinos infrecuentes. Ocasionalmente secretan catecolaminas en cantidades suficientes para causar síntomas. En la mayoría de los casos, los síntomas psicóticos desaparecen con la resección del tumor, lo cual está asociado con la reducción en los niveles de catecolaminas. Caso clínico: Reportamos el caso de una mujer de 56 años de edad con esquizofrenia residual, que comenzó con síntomas agudos caracterizados por palpitaciones, disnea, cefalea y rubor facial, que no respondían al tratamiento antihipertensivo. Al mismo tiempo, tuvo síntomas psicóticos repentinos y positivos, tras un largo periodo de síntomas residuales y negativos. Conclusiones: Con la presentación de este caso queremos resaltar los signos que sugieren inestabilidad autónoma en los pacientes psicóticos, así como la esencialidad de excluir las condiciones somáticas subyacentes. También examinamos las posibles relaciones entre los tumores de las células de la cresta neural que secretan catecolaminas, y la esquizofrenia. (AU)

Anaesthetic management of a dopamine-secreting phaeochromocytoma. / Manejo anestésico de feocromocitoma productor de dopamina.

Pheochromocytomas are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla. Most adrenal pheochromocytomas secrete norepinephrine and epinephrine. Dopamine secreting pheochromocytomas are extremely rare and differs from classic pheochromocytomas in clinical features, posing a significant diagnostic challenge. A 41-year-old women presented to our emergency department because of acute flank colic pain and normotension. The screening abdominal computed tomography scan revealed a left adrenal mass. The laboratory test showed significantly increase in plasma dopamine and 24-hour urine dopamine. During surgical removal the patient remained hypotensive requiring doses of norepinephrine. The patient presented significant hypertensive responde during direct laryngoscopy and intubation.

Feocromocitoma: relato de caso / Pheochromocytoma: case report

Pheochromocytomas are tumors of chromaffin cells in the adrenal medulla that produce, store, metabolize, and secrete catecholamines. Due to increased secretion the patient may present with various symptoms, but elevation of blood pressure is the most common manifestation, and can cause serious complications if not recognized and treated in time. The present report mentions a case of a young male patient who started the picture with severe hypertension, tachycardia and headache, diagnosed with Pheochromocytoma during the investigation of paroxysmal arterial hypertension. It should be noted that early diagnosis, followed by surgical treatment of tumor removal, makes it possible to cure the disease and remission of symptoms.

Os feocromocitomas são tumores das células cromafins da medula adrenal que produzem, armazenam, metabolizam e secretam catecolaminas. Devido à secreção aumentada, o paciente pode apresentar vários sintomas, porém a elevação da pressão arterial é a manifestação mais comum e pode causar sérias complicações se não for reconhecida e tratada a tempo. O presente relato menciona o caso de paciente do sexo masculino, jovem, com início de quadro com hipertensão severa, taquicardia e cefaleia, sendo diagnosticado com feocromocitoma durante a investigação do quadro de hipertensão arterial paroxística. Ressalva-se que o diagnóstico precoce seguido do tratamento cirúrgico de retirada do tumor possibilita a cura da patologia e a remissão dos sintomas.

Clevidipine as an antihypertensive drug in three pheochromocytoma surgeries: Case series / Clevidipino como fármaco antihipertensivo en tres cirugías de feocromocitoma: Serie de casos

Abstract Introduction Laparoscopic adrenalectomy is the treatment of choice of pheochromocytoma. During the first surgical phase (pneumoperitoneum insufflation, tumor and veins handling), there is a risk of hypertensive crisis due to catecholamine release. After tumor excision, patients can suffer relative vasodilation and the residual effect of antihypertensive drugs, which results in arterial hypotension. For that reason, antihypertensive drugs used in the first phase should have a rapid onset of action, short half-life and no residual effect. Methods We report a series of three cases of patients with pheochromocytoma who were treated with laparoscopic adrenalectomy. They all received clevidipine infusion from the beginning of the surgery, before they had presented hypertension, to treat and try to minimize hypertensive peaks. Results In all patients, hypertensive peaks were controlled in a few minutes. After tumor resection, clevidipine infusion was stopped in all cases, and any patient required infusion of vasopressors. Discussion Clevidipine could be a first choice antihypertensive drug in pheochromocytoma surgery. Starting the infusion of clevidipine before the hypertensive peaks could help to make them less pronounced.

Resumen Introducción La adrenalectomía laparoscópica es el tratamiento de elección del feocromocitoma. Durante la primera fase quirúrgica (insuflación de neumoperitoneo, manipulación del tumor y de las venas implicadas), existe el riesgo de que se desencadenen crisis hipertensivas debido a la liberación de catecolaminas. Después de la extirpación del tumor, los pacientes pueden sufrir una vasodilatación relativa y el efecto residual de los fármacos antihipertensivos usados previamente, lo que resulta en hipotensión arterial. Por esa razón, los fármacos antihipertensivos utilizados en la primera fase quirúrgica deben tener rápido inicio de acción, vida media corta y mínimo efecto residual. Métodos Se describe una serie de casos de tres pacientes con feocromocitoma que fueron tratados con adrenalectomía laparoscópica. Todos recibieron infusión de clevidipino desde el comienzo de la cirugía, antes de presentar hipertensión arterial, para así intentar minimizar y tratar rápidamente los posibles picos hipertensivos. Resultados En todos los pacientes los picos hipertensivos se controlaron en pocos minutos. Después de la resección del tumor, la infusión de clevidipino se detuvo en todos los casos y ningún paciente requirió perfusión de vasopresores. Discusión El clevidipino podría ser un fármaco antihipertensivo de primera elección en la cirugía de feocromocitoma. Iniciarlo antes de que ocurran los picos hipertensivos podría ayudar a que sean más leves.

Takotsubo syndrome. / Síndrome de Takotsubo.

Takotsubo syndrome is an acute cardiomyopathy that mimics acute coronary syndrome and is characterized by acute heart failure with reversible ventricular motion abnormalities, in the absence of justifying coronary artery disease. This document offers an exhaustive review of various proposed hypotheses that attempt to explain the pathophysiology of this disease and provides an updated review of the different classifications that have emerged in recent years. In addition, we describe the main clinical characteristics of these patients, the diagnostic tests that must be performed and the most appropriate treatment.

Sex-Related Effects of Prenatal Stress on Region-Specific Expression of Monoamine Oxidase A and β Adrenergic Receptors in Rat Hearts / Efeitos Sexo-Específicos de Estresse Pré-Natal na Expressão Região-Específica de Monoamina Oxidase A e Receptores Adrenérgicos Β no Coração de Ratos

Abstract Background: Prenatal stress may increase risk of developing cardiovascular disorders in adulthood. The cardiotoxic effects of catecholamines are mediated via prolonged adrenergic receptor stimulation and increased oxidative stress upon their degradation by monoamine oxidase A (MAO-A). Objectives: We investigated long-term effects of prenatal stress on β (1, 2, 3) adrenergic receptors and MAO-A gene expression in the hearts of adult rat offspring. Methods: Pregnant rats were exposed to unpredictable mild stress during the third week of gestation. RNA was isolated from left ventricular apex and base of adult offspring. Quantitative PCR was used to measure gene expression in collected ventricular tissue samples. The level of significance was set to p < 0.05. Results: β3 adrenergic receptor mRNA was undetectable in rat left ventricle. β1 adrenergic receptor was the predominantly expressed subtype at the apical and basal left ventricular myocardium in the control females. Male offspring from unstressed mothers displayed higher apical cardiac β1 than β2 adrenergic receptor mRNA levels. However, β1 and β2 adrenergic receptor mRNAs were similarly expressed at the ventricular basal myocardium in males. Unlike males, prenatally stressed females exhibited decreased β1 adrenergic receptor mRNA expression at the apical myocardium. Prenatal stress did not affect cardiac MAO-A gene expression. Conclusions: Collectively, our results show that prenatal stress may have exerted region- and sex-specific β1 and β2 adrenergic receptor expression patterns within the left ventricle.

Resumo Fundamento: Estresse pré-natal pode aumentar os riscos de desenvolver doenças cardiovasculares na idade adulta. Os efeitos cardiotóxicos de catecolaminas são mediados pela estimulação prolongada dos receptores adrenérgicos e pelo aumento do estresse oxidativo após sua degradação pela monoamina oxidase A (MAO-A). Objetivos: Investigamos os efeitos a longo prazo de estresse pré-natal nos receptores β (1, 2, 3) adrenérgicos e na expressão do gene MAO-A nos corações da prole adulta de ratos. Método: Ratas prenhes foram expostas a estresse crônico moderado imprevisível durante a terceira semana de gestação. O RNA foi isolado do ápice e da base do ventrículo esquerdo da prole adulta. Utilizou-se PCR quantitativa em tempo real para medir a expressão gênica nas amostras de tecido ventricular coletadas. O nível de significância foi estabelecido em p < 0,05. Resultados: Foi indetectável o mRNA do receptor adrenérgico β3 no ventrículo esquerdo dos ratos. O receptor adrenérgico β1 foi o subtipo mais expresso no miocárdio ventricular esquerdo apical e basal nas fêmeas controle. A prole masculina das mães não estressadas apresentou níveis cardíacos apicais de mRNA do receptor adrenérgico β1 mais altos do que os de β2. Porém, mRNAs dos receptores adrenérgicos β1 e β2 foram expressos de forma semelhante no miocárdio basal ventricular na prole masculina em geral. Ao contrário da prole masculina, a prole feminina exposta ao estresse pré-natal exibiu uma expressão diminuída do mRNA do receptor adrenérgico β1 no miocárdio apical. O estresse pré-natal não afetou a expressão gênica de MAO-A cardíaca. Conclusões: Coletivamente, nossos resultados mostram que estresse pré-natal pode ter exercido padrões de expressão região- e sexo-específica dos receptores adrenérgicos β1 e β2 no ventrículo esquerdo.

[Diagnostic approach of pheochromocytomas and paragangliomas]. / Enfoque diagnóstico de feocromocitomas y paragangliomas.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumours associated with high morbidity and mortality. Recognizing the clinical presentation is the first step for diagnosis. Biochemical studies may determine an excess of catecholamines and their metabolites. However, the available tests offer varying diagnosis precision. Computed tomography and magnetic resonance are highly sensitive for locating these tumours. Functional tests are reserved for when metastatic and multifocal disease are suspected. One third of the patients have a germline mutation and many genes are involved in the development of these tumours.