Low number of neurosecretory vesicles in neuroblastoma impairs massive catecholamine release and prevents hypertension.

Introduction: Neuroblastoma (NB) is a pediatric cancer of the developing sympathetic nervous system. It produces and releases metanephrines, which are used as biomarkers for diagnosis in plasma and urine. However, plasma catecholamine concentrations remain generally normal in children with NB. Thus, unlike pheochromocytoma and paraganglioma (PHEO/PGL), two other non-epithelial neuroendocrine tumors, hypertension is not part of the usual clinical picture of patients with NB. This suggests that the mode of production and secretion of catecholamines and metanephrines in NB is different from that in PHEO/PGL, but little is known about these discrepancies. Here we aim to provide a detailed comparison of the biosynthesis, metabolism and storage of catecholamines and metanephrines between patients with NB and PHEO. Method: Catecholamines and metanephrines were quantified in NB and PHEO/PGL patients from plasma and tumor tissues by ultra-high pressure liquid chromatography tandem mass spectrometry. Electron microscopy was used to quantify neurosecretory vesicles within cells derived from PHEO tumor biopsies, NB-PDX and NB cell lines. Chromaffin markers were detected by qPCR, IHC and/or immunoblotting. Results: Plasma levels of metanephrines were comparable between NB and PHEO patients, while catecholamines were 3.5-fold lower in NB vs PHEO affected individuals. However, we observed that intratumoral concentrations of metanephrines and catecholamines measured in NB were several orders of magnitude lower than in PHEO. Cellular and molecular analyses revealed that NB cell lines, primary cells dissociated from human tumor biopsies as well as cells from patient-derived xenograft tumors (NB-PDX) stored a very low amount of intracellular catecholamines, and contained only rare neurosecretory vesicles relative to PHEO cells. In addition, primary NB expressed reduced levels of numerous chromaffin markers, as compared to PHEO/PGL, except catechol O-methyltransferase and monoamine oxidase A. Furthermore, functional assays through induction of chromaffin differentiation of the IMR32 NB cell line with Bt2cAMP led to an increase of neurosecretory vesicles able to secrete catecholamines after KCl or nicotine stimulation. Conclusion: The low amount of neurosecretory vesicles in NB cytoplasm prevents catecholamine storage and lead to their rapid transformation by catechol O-methyltransferase into metanephrines that diffuse in blood. Hence, in contrast to PHEO/PGL, catecholamines are not secreted massively in the blood, which explains why systemic hypertension is not observed in most patients with NB.

Optimized procedures for testing plasma metanephrines in patients on hemodialysis.

Diagnosis of pheochromocytomas and paragangliomas in patients receiving hemodialysis is troublesome. The aim of the study was to establish optimal conditions for blood sampling for mass spectrometric measurements of normetanephrine, metanephrine and 3-methoxytyramine in patients on hemodialysis and specific reference intervals for plasma metanephrines under the most optimal sampling conditions. Blood was sampled before and near the end of dialysis, including different sampling sites in 170 patients on hemodialysis. Plasma normetanephrine concentrations were lower (P < 0.0001) and metanephrine concentrations higher (P < 0.0001) in shunt than in venous blood, with no differences for 3-methoxytyramine. Normetanephrine, metanephrine and 3-methoxytyramine concentrations in shunt and venous blood were lower (P < 0.0001) near the end than before hemodialysis. Upper cut-offs for normetanephrine were 34% lower when the blood was drawn from the shunt and near the end of hemodialysis compared to blood drawn before hemodialysis. This study establishes optimal sampling conditions using blood from the dialysis shunt near the end of hemodialysis with optimal reference intervals for plasma metanephrines for the diagnosis of pheochromocytomas/paragangliomas among patients on hemodialysis.

Serial Hydrolysis for the Simultaneous Analysis of Catecholamines and Steroids in the Urine of Patients with Alopecia Areata.

Catecholamines and steroids are well-known neurotransmitters and hormones that rapidly change the excitability of neurons. Alopecia areata is a disease for which the exact cause is unknown, but it is considered to be associated with stress, and so the simultaneous analysis of catecholamines and steroids is required for the diagnosis of alopecia areata. Thus, we herein report the simultaneous analysis of catecholamines and steroids bearing different functional groups for the first time, during which it was necessary to carry out a serial hydrolysis procedure. Following hydrolysis of the urine samples to produce the free forms from the urinary conjugates, ethyl acetate extractions were carried out, and chemical derivatization was performed using dansyl chloride to increase the sensitivity of the liquid chromatography-tandem mass spectrometry method. The matrix effects and recoveries of this analytical method were validated, giving values of 85.4-122.9% and 88.8-123.0%, respectively. In addition, the method accuracy and precision were assessed, giving values of 0.4-21.5% and 2.0-21.6% for the intra-day and inter-day precisions, respectively. This validated method was then applied to identify differences between patients with and without alopecia areata, wherein the metanephrine content was found to be significantly higher in the alopecia areata patient group. This quantitative profiling method can also be applied to steroid-dependent diseases, as well as catecholamine-related diseases.

False elevations in urinary metanephrines: under-recognised pitfall with 24-hour urinary volume collection.

One pitfall in 24-hour urine collection is the input of incorrect urinary volume by the reference laboratory. This may lead to an incorrect diagnosis of pheochromocytoma or paraganglioma. A 48-year-old African-American woman was seen in the clinic for an elevated 24-hour urine metanephrine screen during workup for secondary hypertension. Urine volume was found to be incorrectly inputted by the lab as 9750 mL rather than 975 mL. The urinary metanephrines were then recalculated and the 24-hour urinary metanephrines resulted within normal limits. This case highlights this unique and potentially under-recognised error in testing with 24-hour urine volume collection.

Effect of Supplementation with Saccharomyces Boulardii on Academic Examination Performance and Related Stress in Healthy Medical Students: A Randomized, Double-Blind, Placebo-Controlled Trial.

In recent years, bacterial probiotic dietary supplementation has emerged as a promising way to improve cognition and to alleviate stress and anxiety; however, yeast probiotics have not been tested. The aim of the present study was to determine whether 30-day supplementation with Saccharomyces boulardii enhances academic performance under stress and affects stress markers. The trial was retrospectively registered at clinicaltrials.gov (NCT03427515). Healthy medical students were randomized to supplement their diet with Saccharomyces boulardii CNCM I-1079 or placebo before sitting for an academic examination, which served as a model of stress. The grades of a final examination adjusted to subject knowledge tested in non-stressful conditions was used as a primary outcome measure. Psychometrically evaluated state anxiety, cortisol and metanephrine salivary levels, and pulse rate were tested at a non-stressful time point before the intervention as well as just before the stressor. Fifty enrolled participants (22.6 ± 1.4 years of age, 19 males) completed the trial in the Saccharomyces and placebo arms. Supplementation with Saccharomyces did not significantly modify examination performance or increase in state anxiety, salivary cortisol, and metanephrine. However, the intervention resulted in higher increase in pulse rate under stress as compared to placebo by 10.4 (95% CI 4.2-16.6) min-1 (p = 0.0018), and the effect positively correlated with increase in salivary metanephrine (Pearson's r = 0.35, 95% CI 0.09-0.58, p = 0.012). An intention-to-treat analysis was in line with the per-protocol one. In conclusion, supplementation with Saccharomyces boulardii CNCM I-1079 appears largely ineffective in improving academic performance under stress and in alleviating some stress markers, but it seems to increase pulse rate under stress, which may hypothetically reflect enhanced sympathoadrenal activity.

What do you need to know about mass spectrometry? A brief guide for endocrinologists.

In routine hormonology, liquid chromatography mass spectrometry (LCMS) is now an established technique for androgen, urinary cortisol and metanephrine assay. It has the undeniable advantage of great analytical specificity, but with sensitivity that clearly depends on financial investment in a very high-end spectrometer. We describe the general principles of LCMS and the routine applications so far developed in hormonology. The purpose is to familiarise endocrinologists with the techniques under development and their pros and cons.

Rendimiento de las metanefrinas libres plasmáticas en el diagnóstico de los feocromocitomas y paragangliomas en la población asturiana / Performance of plasma free metanephrines in diagnosis of pheochromocytomas and paragangliomas in the population of Asturias

Introducción: Los feocromocitomas y paragangliomas son tumores poco frecuentes cuyos síntomas más conocidos son hipertensión arterial, palpitaciones, cefalea y diaforesis. Sin embargo, su identificación clínica no es fácil. Por ello, se utilizan pruebas bioquímicas que permitan un diagnóstico precoz, destacando las metanefrinas. El objetivo de este estudio fue evaluar el rendimiento diagnóstico de las metanefrinas libres plasmáticas (MLP) y verificar la transferibilidad de los valores de referencia utilizados. Métodos: Las MLP fueron cuantificadas mediante cromatografía líquida de alta resolución acoplada a espectrometría de masas. Otras pruebas bioquímicas evaluadas (catecolaminas en plasma, metanefrinas, catecolaminas y ácido vanilmandélico en orina) fueron analizadas por cromatografía líquida de alta resolución con detección electroquímica. Se revisaron las solicitudes de dichas pruebas del 01/09/2015 al 31/10/2017 y se estimaron los valores de referencia (documento EP28-A3c) y los parámetros de variabilidad biológica (método de Fraser) de las MLP. Resultados: Se estudiaron 1.279 pacientes (61,3% mujeres), con edades entre 0-90 años, incluyendo 19 casos de feocromocitoma/paraganglioma. Las solicitudes bioquímicas fueron: MLP (n=662), catecolaminas urinarias (n=589), metanefrinas urinarias (n=586), ácido vanilmandélico urinario (n=513) y catecolaminas plasmáticas (n=228). Las pruebas con mayor sensibilidad fueron las metanefrinas fraccionadas urinarias (91,7%) y las MLP (82,4%). Cuando se comparó el rendimiento en pacientes con ambas pruebas (n=243), estas detectaron los mismos casos (90,9%), pero las MLP fueron más específicas (93,5 vs. 88,8%). Para la normetanefrina plasmática se observó una asociación significativa con la edad (rho=0,19; p<0,0001). Conclusión: Las MLP y las metanefrinas fraccionadas urinarias son las pruebas bioquímicas que ofrecen un mayor rendimiento en el diagnóstico de los feocromocitomas/paragangliomas

Introduction: Pheochromocytoma and paraganglioma are uncommon tumors whose best known symptoms include high blood pressure, palpitations, headache, and sweating. Clinical identification is not easy, however, and requires biochemical tests that allow for early diagnosis, including measurement of metanephrines levels. The aim of this study was to assess the diagnostic performance of plasma free metanephrines (PMETs) and to verify the transferability of the reference values used. Methods: PMETs levels were measured by liquid chromatography coupled to tandem mass spectrometry. Other biochemical tests evaluated (plasma catecholamine, urine metanephrine, catecholamine and vanilmandelic acid levels) were performed by liquid chromatography with electrochemical detection. Requests of these tests from 01/09/2015 to 31/10/2017 were reviewed, and both the reference values (document EP28-A3c) and the parameters of biological variation (Fraser method) for PMETs were estimated. Results: The study sample consisted of 1,279 patients (61.3% females) aged 0-90 years, including 19 with pheochromocytoma/paraganglioma. Tests requested included: PMETs (n=662), catecholamines (n=589), metanephrines (n=586), and vanilmandelic acid (n=513) in urine, and plasma catecholamines (n=228). Tests with higher sensitivity were urinary fractionated metanephrines (91.7%) and PMETs (82.4%). When performance was compared in patients with both tests (n=243), they detected the same number of tumors (90.9%), but PMETs showed greater specificity (93.5% vs 88.8%). Plasma normetanephrine levels showed a significant association with age (rho=0.19, P<.0001). Conclusion: PMETs and urinary fractionated metanephrines are the biochemical tests with better performance in diagnosis of pheochromocytomas/paragangliomas

Catecholamine and Metanephrine Levels in Breast Milk Before and After Paraganglioma Resection.

Background: Catecholamine and metanephrine transfer into breast milk in the setting of secreting paraganglioma or pheochromocytoma has not been previously described. Materials and Methods: We present an investigation in which we measured catecholamine and metanephrine levels in the breast milk in a single patient undergoing resection of a paraganglioma at 5 weeks postpartum. Results:As expected, levels were elevated preoperatively and decreased rapidly after resection. Conclusion:This information may be clinically relevant for patient management when pheochromocytoma or paraganglioma resection is delayed with respect to the delivery of the infant or in the postoperative monitoring of the patient's status.

Plasma free metanephrines for diagnosis of neuroblastoma patients.

INTRODUCTION: A substantial number of patients with neuroblastoma (NB) have increased excretion of catecholamines and metanephrines. Here, we have investigated the diagnostic role of plasma free metanephrines (PFM), metanephrine (MN), normetanephrine (NMN) and 3-methoxytyramine (3MT) for NB, the most common extra-cranial solid tumour in children. METHODS: PFM were quantified by using a commercial IVD-CE LC-MS/MS method on a TSQ Quantiva coupled to an Ultimate 3000. The method was further validated on 103 samples from pediatric subjects (54 patients with histologically confirmed NB and 49 age and sex matched controls). Correlations between PFM concentrations with clinical factors were tested. We directly compared MN, NMN, and 3MT concentrations in matched plasma and urine samples of NB patients (n = 29). RESULTS: 3MT and NMN showed an excellent diagnostic performance with very high specificity (100% and 95.8%, respectively) and sensitivity (88.2% and 80.4%). ROC curves were obtained (AUC of 0.93 and 0.91 for 3MT and NMN, respectively) and optimal cut-offs that could discriminate between controls and NB patients were defined. A positive correlation between NMN levels in urine and plasma (p = .0017) was found. DISCUSSION: The determination of plasma 3MT and NMN should be taken in consideration as a new diagnostic tool for NB. Validation in prospective clinical studies in comparison to urinary catecholamines and metanephrines is warranted.

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

Los feocromocitomas y paragangliomas son tumores neuroendócrinos poco frecuentes y con alta morbimortalidad. Reconocer las distintas formas de presentación es el paso diagnóstico inicial. El estudio bioquímico permite determinar el exceso de catecolaminas y sus metabolitos. Sin embargo, las determinaciones disponibles ofrecen diferente precisión diagnóstica. La tomografía computada y la resonancia magnética permiten localizar estos tumores con una alta sensibilidad. Los estudios funcionales se reservan para sospecha de enfermedad metastásica y para tumores múltiples. Un tercio de los pacientes presenta una mutación genética germinal y varios genes están implicados en el desarrollo de estos tumores

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

[Biological diagnosis of pheochromocytoma: is there an interest in urinary metanephrines measurement over 3 consecutive days?] / Diagnostic biologique du phéochromocytome : le dosage des dérivés méthoxylés urinaires sur 3 jours consécutifs présente-t-il un intérêt ?

Pheochromocytoma and paraganglioma are neuroendocrine tumors characterized by a catecholamine production potential. The biochemical diagnosis for this type of tumor is carried out through the metanephrine titration on 24-hours urines. Some authors have suggested that the sensitivity of the test could be improved by sampling and analyzing urines 3 days in a row (cycle) versus a unique measurement but this method has never been fully evaluated. The goal of this study was to establish a comparison of diagnosis performances between urinary metanephrines measurement for 3 consecutive days, and metanephrines measurement on a unique 24-hour sample. Patients of Brest Regional University Hospital whose 3-consecutive day 24-hour urine samples had been analyzed from January 2011 to May 2017 were included in this study. The primary endpoint was the comparison of diagnostic performances of urinary metanephrine titration over a single day versus 3 consecutive days. Eighty-two patients for a total of 103 cycles among which 7 revealed a pheochromocytoma were analyzed. ROC curve analysis shows that the metanephrine cycle titration method is more efficient than the metanephrine single titration method (metanephrine: AUC=0.881 against 0.826 respectively; normetanephrine: AUC=0.946 against 0.901 respectively). Urinary titration over 3 days allows the diagnosis of 100% (7/7) of pheochromocytomas against 85.7% (6/7) for the the single urinary titration. In conclusion, metanephrine titration over 3 consecutive days of 24-hours urine samples shows a better sensitivity and better diagnosis performances for detecting pheochromocytoma and paraganglioma than the single titration method.

Clevidipino como antihipertensivo en la cirugía de feocromocitoma / Clevidipine for hypertension treatment in pheochromocytoma surgery

El feocromocitoma es un tumor productor de catecolaminas y su tratamiento de elección es la adrenalectomía laparoscópica. Durante la insuflación del neumoperitoneo y la manipulación tumoral hay alto riesgo de liberación masiva de catecolaminas y crisis hipertensivas. Tras la exéresis tumoral es frecuente la hipotensión arterial grave por vasodilatación relativa y por el efecto residual de los fármacos antihipertensivos utilizados. Presentamos el caso clínico de un paciente con feocromocitoma intervenido de adrenalectomía laparoscópica. Durante la manipulación quirúrgica hubo un pico hipertensivo brusco que pudo controlarse rápidamente con clevidipino en perfusión. Tras la resección tumoral se detuvo la perfusión y no se produjo hipotensión arterial en ningún momento. El clevidipino es un nuevo antagonista del calcio intravenoso con inicio de acción rápido y vida media corta que no tiene efecto residual y no causa hipotensión tras la resección tumoral, por lo que puede ser un fármaco de primera elección esta cirugía

Pheochromocytoma is a catecholamine-producing tumour and laparoscopic adrenalectomy is its treatment of choice. During pneumoperitoneum insufflation and tumour handling there is a high risk of massive catecholamine release and hypertensive crisis. After tumour excision, severe arterial hypotension is a common effect, due to relative vasodilation and the residual effect of antihypertensive drugs. We report the case of a patient with pheochromocytoma who was treated with laparoscopic adrenalectomy. During surgical manipulation there was a sudden hypertensive peak that could be controlled quickly with clevidipine infusion. After tumour resection, clevidipine perfusion was stopped and there were no arterial hypotension episodes. Clevidipine is a new intravenous calcium antagonist with rapid onset of action and short half-life that has no residual effect and does not produce arterial hypotension after tumour resection. For these reasons, it can be a first-choice drug for this kind of surgery

Adrenal hormones and circulating leukocyte subtypes in stroke patients treated with reperfusion therapy.

Ischemic stroke sets in motion a dialogue between the central nervous and the immune systems that includes the sympathetic/adrenal system. We investigated the course of immune cells and adrenocortical and adrenomedullary effectors in a cohort of 51 patients with acute stroke receiving reperfusion therapy (intravenous alteplase or mechanical thrombectomy) and its correlation with stroke outcomes and infarct growth. Cortisol increased rapidly and fleetingly after stroke, but 39% of patients who had larger infarctions on admission showed a positive delta cortisol at day 1. It was associated with enhanced infarct growth (p = 0.002) and poor outcome [OR (95% CI) 5.30 (1.30-21.69)], and correlated with less lymphocytes and T cells at follow up. Likewise, fewer circulating lymphocytes, T cells, and Tregs were associated with infarct growth. By contrast, metanephrines did not increase at clinical onset, and decreased over time. Higher levels of NMN correlated with more Treg and B cells. Eventually, complete reperfusion at the end of therapy headed the identification of more circulating Tregs at day 1. Then activation of cortical or medullar compartments of the adrenal gland result in specific signatures on leukocyte subpopulations. Manipulation of the adrenal gland hormone levels warrants further investigation.

High specificity of spot urinary free metanephrines in diagnosis and prognosis of pheochromocytomas and paragangliomas by HPLC with electrochemical detection.

BACKGROUND: The metanephrines (MNs) in plasma and urine were proposed as biomarkers for the diagnosis of pheochromocytomas and paragangliomas (PPGLs). However, plasma free MNs and 24h urinary fractionated MNs were not satisfactory enough in specificity for the diagnosis of PPGLs. Moreover, the collection of 24h urine was inconvenient. This work examined the diagnostic and prognostic efficiency of free MNs in spot urine for PPGLs. METHODS: We measured free MNs concentration in spot urine and plasma of 28 PPGLs patients and 155 control subjects by HPLC with electrochemical detection. Postoperative free MNs levels in spot urine and plasma of 14 PPGLs patients were also determined. Creatinine (Cr) concentration was used for the correction of urine volume. RESULTS: The specificity of spot urinary free MNs/Cr in the diagnosis of PPGLs was significantly higher than that of plasma free MNs [normetanephrine (NMN), 98.7% (95.4%-99.8%) vs 93.0% (87.4%-96.6%); metanephrine (MN), 93.6% (88.5%-96.9%) vs 84.5% (77.5%-90.0%)]. Meanwhile, the positive likelihood ratios for spot urinary free NMN/Cr and MN/Cr were 69.21 and 13.29, compared with 12.68 and 5.30 for plasma free NMN and MN, respectively. For the PPGLs patients underwent surgery, the plasma free MNs level appeared an abnormal elevation and yielded false-positive results for some patients. Our findings were validated in an independent cohort, resulting in the specificity of 100% for both urinary free NMN/Cr and MN/Cr, and 97.3% and 83.8% for plasma free NMN and MN, respectively. CONCLUSIONS: Spot urinary free MNs/Cr, superior to plasma free MNs, presented a promising biomarker for the diagnosis and prognosis of PPGLs.

A Case Report of Cystic Pheochromocytoma.

BACKGROUND Pheochromocytoma is a rare catecholamine-producing tumor with an estimated incidence of less than 0.1% in the global population. We present a case of cystic pheochromocytoma that was diagnosed as an incidental finding. The patient presented with abdominal pain and had a history of hypertension. CASE REPORT A 64-year-old man with hypertension presented with a clinical history of intermittent abdominal pain for one year. He denied sweating, palpitations, headache or back pain. He was found to have an elevated blood pressure of 170/90 and no palpable abdominal mass. Contrast-enhanced computed tomography (CT) imaging of the abdomen and pelvis were performed that showed cystic mass measuring 9 cm in diameter arising from the left adrenal gland with contrast-enhancing mural nodules. Magnetic resonance imaging (MRI) confirmed the cystic nature of the mass. Laboratory analysis showed an elevated plasma normetanephrine (NMN) of 1,087 pg/ml and metanephrine (MN) of 372 pg/ml; 24-hour urine showed elevated levels of NMN and MN, 3,002 mg/24 h and 1,596 mg/24 h, respectively. Given the laboratory and radiologic findings, a diagnosis of cystic pheochromocytoma was made. After controlling blood pressure with the alpha-blocker, doxazosin, the patient was hydrated and scheduled for an elective adrenalectomy. The histopathology of the excised adrenal gland was consistent with a cystic pheochromocytoma. CONCLUSIONS Cystic pheochromocytoma is a very rare tumor that may present without symptoms. The clinical course of cystic pheochromocytoma is similar to that of solid pheochromocytoma. Early surgical intervention is recommended, following blood pressure control with an alpha-blocker, and adequate hydration.

Accuracy of recommended sampling and assay methods for the determination of plasma-free and urinary fractionated metanephrines in the diagnosis of pheochromocytoma and paraganglioma: a systematic review.

PURPOSE: To determine the accuracy of biochemical tests for the diagnosis of pheochromocytoma and paraganglioma. METHODS: A search of the PubMed database was conducted for English-language articles published between October 1958 and December 2016 on the biochemical diagnosis of pheochromocytoma and paraganglioma using immunoassay methods or high-performance liquid chromatography with coulometric/electrochemical or tandem mass spectrometric detection for measurement of fractionated metanephrines in 24-h urine collections or plasma-free metanephrines obtained under seated or supine blood sampling conditions. RESULTS: Application of the Standards for Reporting of Diagnostic Studies Accuracy Group criteria yielded 23 suitable articles. Summary receiver operating characteristic analysis revealed sensitivities/specificities of 94/93% and 91/93% for measurement of plasma-free metanephrines and urinary fractionated metanephrines using high-performance liquid chromatography or immunoassay methods, respectively. Partial areas under the curve were 0.947 vs. 0.911. Irrespective of the analytical method, sensitivity was significantly higher for supine compared with seated sampling, 95 vs. 89% (p < 0.02), while specificity was significantly higher for supine sampling compared with 24-h urine, 95 vs. 90% (p < 0.03). Partial areas under the curve were 0.942, 0.913, and 0.932 for supine sampling, seated sampling, and urine. Test accuracy increased linearly from 90 to 93% for 24-h urine at prevalence rates of 0.0-1.0, decreased linearly from 94 to 89% for seated sampling and was constant at 95% for supine conditions. CONCLUSIONS: Current tests for the biochemical diagnosis of pheochromocytoma and paraganglioma show excellent diagnostic accuracy. Supine sampling conditions and measurement of plasma-free metanephrines using high-performance liquid chromatography with coulometric/electrochemical or tandem mass spectrometric detection provides the highest accuracy at all prevalence rates.

Tumor carcinoide sobre teratoma ovárico quístico / Carcinoid tumor on cystic ovarian teratoma

No disponible

Hipertensión arterial de díficil control asociada a masa abdominal / Resistant hypertension associated to an abdominal mass

La palpación de una masa abdominal y la presencia de hipertensión de difícil control debe hacernos pensar en la posible existencia de un feocromocitoma. El feocromocitoma maligno representa entre el 2 y el 11% de los tumores neuroendocrinos, productor de catecolaminas, en el que la tríada clínica típica no siempre está presente, siendo la clínica bastante variable. El patrón nodipper en la monitorización ambulatoria de la presión arterial (MAPA), la determinación de metanefrinas plasmáticas y cromogranina A, junto a las pruebas de imagen realizadas, confirmaron el diagnóstico. Son de mal pronóstico, con una supervivencia menor del 50% a los 5 años. Su tratamiento se basa principalmente en la exéresis del tumor. Suelen ser radiorresistentes y la respuesta a la quimioterapia es mínima, por lo que el tratamiento suele tener un enfoque principalmente paliativo (AU)

Palpation of an abdominal mass and the presence of difficult-to-control hypertension should make us consider the possible existence of a pheochromocytoma. Malignant pheochromocytoma accounts for 2-11% of neuroendocrine tumors, catecholamine producing tumors, in which the typical clinical triad is not always present because of the variety of their clinical presentations. Diagnosis is confirmed through the nondipper pattern in the ambulatory blood pressure monitoring (ABPM) study, the measurement of plasma metanephrines and chromogranin A, as well as the imaging tests. Pheochromocytomas have a bad prognosis, survival being less than 50% at 5 years. The main treatment is tumor excision. They are usually resistant to radiotherapy, and response to chemotherapy is minimum. Thus, the treatment approach is often mainly palliative (AU)