RESUMO
The description of the child aged 5 months with the von Hippel-Lindau syndrome without any manifestations of this syndrome is presented. The reason for the molecular genetic examination was the presence of cases of this syndrome in the family (mother and sister). The heterozygous variant c.355T>C p.F119L was found in the VHL gene. An objective examination revealed no pathology. A comprehensive laboratory and instrumental examination aimed at searching for components of the von Hippel-Lindau syndrome, including a blood test for metanephrines and normetanephrines, ultrasound of the abdominal organs, examination of the fundus, also did not reveal any abnormalities. Given the results of molecular genetic diagnosis, the child remains under observation and will undergo regular examinations to identify components of the von Hippel-Lindau syndrome, including blood/urine tests for normetanephrines.
Assuntos
Doença de von Hippel-Lindau , Criança , Animais , Humanos , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/genética , Síndrome , Genes Reguladores , Abomaso , Fundo de Olho , NormetanefrinaRESUMO
INTRODUCTION: Incidentaloma is an adrenal tumor detected during diagnostic imaging performed for extraadrenal causes. Evaluation of metanephrine concentrations in a 24hour urine collection can be a significant challenge in patients with multiple medications and comorbidities. OBJECTIVES: The aim of this study was to evaluate the effect of commonly used groups of drugs on metanephrine levels in the 24hour urine collection. PATIENTS AND METHODS: A total of 1051 patients with adrenal mass below 10 Hounsfield units on unenhanced computed tomography were included in the study. Patients diagnosed with Cushing or Conn syndrome, adrenal carcinoma, pheochromocytoma, active extraadrenal malignant neoplasms, and exacerbation of severe illnesses were excluded. Metanephrine, normetanephrine, and 3methoxytyramine in the 24hour urine collection were measured by highperformance liquid chromatography with electrochemical detection. Information on concomitant medication (ßblockers, calcium channel blockers [CCBs], loop diuretics, thiazide diuretics, potassiumsparing diuretics, αblockers, angiotensinconverting enzyme inhibitors / angiotensin II receptor blockers, metformin, nonmetformin antidiabetic drugs [NMADs], lipidlowering drugs, proton pump inhibitors, levothyroxine, thyreostatics, antidepressants, neuroleptics, benzodiazepines, glucocorticosteroids, inhaled Breceptor agonists, and ipratropium) was collected from each patient. RESULTS: The urinary excretion of normetanephrine was significantly higher in the patients on ßblockers, CCBs, loop diuretics, αblockers, NMADs, and neuroleptics. αBlockers increased urine metanephrine concentration, and NMADs, antidepressants, and glucocorticosteroids lowered it. There was no association between the analyzed drugs and urinary 3methoxytyramine level. CONCLUSIONS: Many drug groups interfere with the measurement of urinary fractionated metanephrines. These interactions should be taken into account during interpretation of a hormonal evaluation, as they can be crucial for further management, especially for making a decision on surgical treatment.
Assuntos
Neoplasias das Glândulas Suprarrenais , Antipsicóticos , Dopamina/análogos & derivados , Humanos , Metanefrina/urina , Normetanefrina/urina , Neoplasias das Glândulas Suprarrenais/cirurgia , Antidepressivos , DiuréticosRESUMO
This study aimed to elucidate the clinical diagnostic value of plasma catecholamines and their metabolites for pheochromocytoma and paraganglioma (PPGL)-induced secondary hypertension using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS). The study population included 155 patients with PPGL that were divided into the PPGL with hypertension (n = 79) and a PPGL without hypertension (n = 76) groups, and 90 healthy volunteers and 90 patients with primary hypertension as the control groups. UPLC-MS/MS was performed to detect plasma levels of catecholamines and their metabolites, including dopamine, vanillylmandelic acid (VMA), norepinephrine, metanephrine, and normetanephrine. Receiver operating characteristic curves were generated to analyze the diagnostic value of the plasma levels of catecholamines and their metabolites in PPGL-induced secondary hypertension. Patients in the primary hypertension and PPGL without hypertension groups had higher levels of dopamine, VMA, norepinephrine, metanephrine, and normetanephrine than patients in the normal group (all p < .05). On the other hand, patients in the PPGL with hypertension group had higher levels of dopamine, VMA, norepinephrine, metanephrine, and normetanephrine than patients in the normal, primary hypertension, and PPGL without hypertension groups (all p < .05). Collectively, our findings showed that dopamine, VMA, norepinephrine, metanephrine, and normetanephrine are all effective biomarkers for the diagnosis of PPGL and PPGL-induced secondary hypertension.
Assuntos
Neoplasias das Glândulas Suprarrenais , Hipertensão , Ácidos Mandélicos , Paraganglioma , Feocromocitoma , Humanos , Catecolaminas , Feocromocitoma/complicações , Feocromocitoma/diagnóstico , Metanefrina , Normetanefrina , Dopamina , Cromatografia Líquida/métodos , Espectrometria de Massa com Cromatografia Líquida , Hipertensão/diagnóstico , Espectrometria de Massas em Tandem/métodos , Paraganglioma/complicações , Paraganglioma/diagnóstico , Norepinefrina , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Hipertensão Essencial/diagnósticoRESUMO
Measurements of plasma metanephrines and methoxytyramine provide a sensitive test for diagnosis of pheochromocytoma/paraganglioma. False-positive results remain a problem, particularly in patients taking norepinephrine reuptake-blocking drugs. Therefore, in this retrospective observational study, we measured plasma metanephrines and methoxytyramine in 61 patients taking norepinephrine reuptake blockers (tricyclic antidepressants or serotonin-norepinephrine reuptake inhibitors) and 17 others taking selective serotonin reuptake inhibitors, all without pheochromocytoma/paraganglioma. We highlight a singular case with strongly elevated plasma normetanephrine and methoxytyramine concentrations associated with norepinephrine reuptake blockade. Data were compared to results from 252 and 1804 respective patients with and without tumors. Plasma normetanephrine was 40% higher (P < 0.0001) in patients on norepinephrine reuptake blockers and methoxytyramine was 127% higher (P = 0.0062) in patients taking tricyclic antidepressants compared to patients not taking uptake blockers and without tumors. The corresponding false-positive rates rose (P < 0.0001) from 4.8% to 23.0% for normetanephrine and from 0.9% to 28.6% for methoxytyramine. Selective serotonin reuptake inhibitors did not increase plasma concentrations of metabolites. In the highlighted case, plasma normetanephrine and methoxytyramine were elevated more than six times above upper reference limits. A pheochromocytoma/paraganglioma, however, was excluded by functional imaging. All biochemical test results normalized after discontinuation of norepinephrine reuptake blockers. These findings clarify that norepinephrine reuptake blockers usually result in mild elevations of normetanephrine and methoxytyramine that, nevertheless, significantly increase the number of false-positive results. There can, however, be exceptions where increases in normetanephrine and methoxytyramine reach pathological levels. Such exceptions may reflect failure of centrally mediated sympathoinhibition that normally occurs with the norepinephrine reuptake blockade.
Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/tratamento farmacológico , Feocromocitoma/diagnóstico , Normetanefrina , Antidepressivos Tricíclicos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Metanefrina , Paraganglioma/tratamento farmacológico , Paraganglioma/diagnóstico , Norepinefrina , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/diagnósticoRESUMO
The patient, a 40-year-old woman, was diagnosed as having a functional right vagal paraganglioma (PGL) 15 years after undergoing resection for a retroperitoneal PGL. 123I-MIBG scintigraphy showed no accumulation, but as the blood noradrenaline and urinary normetanephrine concentrations were elevated, the tumor was judged as being functional, and surgery was scheduled. The patient was started on doxazosin infusion and embolization of the tumor feeding vessel was performed before the surgery. Intraoperative examination showed that the tumor was contiguous with the vagal nerve, necessitating combined resection of the vagal nerve with the tumor. Postoperatively, the catecholamine levels returned to normal range. Histopathologically, the tumor was diagnosed as a moderately differentiated, intermediate-malignant-grade PGL, with a GAPP score of 4 to 6. No non-chromaffin tissue was observed in the tumor background, so that the functional vagal PGL was considered as a sporadic metachronous tumor rather than as a metastasis from the retroperitoneal PGL. More than half of head and neck paragangliomas (HNPGLs) are reported to arise in the carotid body, and about 5% from the vagal nerve. In addition, HNPGLs rarely produce catecholamines. Herein, we consider the relationship with the previously resected retroperitoneal PGL based on a review of the literature.
Assuntos
Paraganglioma , Neoplasias Retroperitoneais , Humanos , Feminino , Adulto , Neoplasias Retroperitoneais/cirurgia , Neoplasias Retroperitoneais/patologia , Paraganglioma/cirurgia , Paraganglioma Extrassuprarrenal/cirurgia , Paraganglioma Extrassuprarrenal/patologia , Normetanefrina/urina , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/cirurgia , Neoplasias dos Nervos Cranianos/cirurgia , Neoplasias dos Nervos Cranianos/patologia , Doenças do Nervo Vago/cirurgia , Embolização Terapêutica , Norepinefrina/sangue , Nervo VagoRESUMO
Purpose: To evaluate the rate of recurrence among patients with pheochromocytomas and sympathetic paragangliomas (PGLs; together PPGLs) and to identify predictors of recurrence (local recurrence and/or metastatic disease). Methods: This retrospective multicenter study included information of 303 patients with PPGLs in follow-up in 19 Spanish tertiary hospitals. Recurrent disease was defined by the development of local recurrence and/or metastatic disease after initial complete surgical resection. Results: A total of 303 patients with PPGLs that underwent 311 resections were included (288 pheochromocytomas and 15 sympathetic PGLs). After a median follow-up of 4.8 years (range 1-19), 24 patients (7.9%) had recurrent disease (3 local recurrence, 17 metastatic disease and 4 local recurrence followed by metastatic disease). The median time from the diagnosis of the PPGL to the recurrence was of 11.2 months (range 0.5-174) and recurrent disease cases distributed uniformly during the follow-up period. The presence of a pathogenic variant in SDHB gene (hazard ratio [HR] 13.3, 95% CI 4.20-41.92), higher urinary normetanephrine levels (HR 1.02 per each increase in standard deviation, 95% CI 1.01-1.03) and a larger tumor size (HR 1.01 per each increase in mm, 95% CI 1.00-1.02) were independently associated with disease recurrence. Conclusion: The recurrence of PPGLs occurred more frequently in patients with SDHB mutations, with larger tumors and with higher urinary normetanephrine levels. Since PPGL recurrence may occur at any time after the initial PPGL diagnosis is performed, we recommend performing a strict follow-up in all patients with PPGLs, especially in those patients with a higher risk of recurrent disease.
Assuntos
Neoplasias das Glândulas Suprarrenais , Neoplasias Encefálicas , Segunda Neoplasia Primária , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/patologia , Normetanefrina , Recidiva Local de Neoplasia , Paraganglioma/patologia , Neoplasias das Glândulas Suprarrenais/diagnósticoRESUMO
O avanço tecnológico na obtençäo de imagens em medicina (ultrassonografia, tomografia computadorizada e ressonância nuclear magnética) tem proporcionado uma precisäo de detalhes cada vez maior. Por isso, a incidência de achados de massas acidentais está aumentando na mesma proporçäo, obrigando-nos a deparar com novos desafios diagnósticos e terapêuticos. O incidentaloma da adrenal apresenta-se nesta categoria, constituindo um problema diagnóstico e um dilema terapêutico. O feocromocitoma é um tumor raro, que incide em apenas 0,1 por cento dos indivíduos hipertensos e se carateriza por extrema variabilidade na sua expressäo clínica. Raramente o tumor é clinicamente silencioso, porém, frequentemente, seu diagnóstico é estabelecido somente após remoçäo de um incidentaloma adrenal ou autópsia. Neste relato de caso apresentamos uma paciente assintomática, portadora de feocromocitoma silencioso, com aumento apenas dos níveis de normetanefrinas urinárias, alertando para a importância da investigaçäo funcional destas massas encontradas incidentalmente. Os resultados alterados em apenas um dos metabólitos urinários de catecolaminas (HPLC) confirmam achados prévios, de serem estes os mais sensíveis para investigaçäo dos incidentalomas adrenais na detecçäo de feocromocitomas.
Assuntos
Humanos , Feminino , Adulto , Neoplasias das Glândulas Suprarrenais/diagnóstico , Normetanefrina/urina , Feocromocitoma/diagnóstico , Neoplasias das Glândulas Suprarrenais/urina , Feocromocitoma/urinaRESUMO
En este trabajo se han compilado los distintos modos cromatográficos y sistemas de detección utilizados en la cromatografía líquida de alta resolución de aminas biogénicas. Se indican las características generales del intercambio catiónico, fase reversa, fase reversa de pares iónicos y cromatografía de partición con fase reversa de pares iónicos. También se analizan comparativamente la detección UV, detección fluorimétrica usando fluorescencia nativa o bien derivatización pre- y postcolumna y detección electroquímica de gran utilidad para esta extensa familia de compuestos. Se dan ejemplos de aplicación de interés en el campo bioquímico-clínico, con el análisis de ácido homovainillínico, ácido 3,4-dihidroxifenilacético y ácido 5-hidroxiindolacético en líquido cefalorraquídeo, metanefrinas, ácido 3,4-dihidroxifenilacético, catecolaminas, ácidos urinarios y 3-metoxi-4-hidroxifenilglicol en orina, catecolaminas y 3-metoxi-4-hidroxifenilglicol en plasma, catecolaminas, 3-metoxi-4-hidroxifenilglicol y otros neurotransmisores en cerebro de rata. Se discuten, también, los tratamientos previos requeridos especialmente para orina y plasma, así como las condiciones de conservación y su incidencia en los resultados obtenidos