Screening for phaeochromocytoma in patients with acute cerebrovascular disease: Is it necessary?

@#Introduction: Phaeochromocytoma may present with uncontrolled hypertension leading to haemorrhagic stroke (HS), ischaemic stroke (IS) and transient ischaemic attack (TIA). False elevation in the levels of CATS/ METS has been reported in acute cerebrovascular disease. Our aim was to analyse the frequency and pattern of elevations of CATS/METS in patients with acute cerebrovascular disease and to determine associated factors. Materials and Methods: This is a retrospective study of 112 samples of CATS/ METS received by the laboratory over a two-year period, from patients with acute cerebrovascular disease. CATS/METS were measured using LC/MS/MS method. Clinical details and CATS/METS level were obtained from the database. Mann-Whitney U test and Kruskal Wallis test were used for statistical analysis. These statistical analyses were performed using SPSS v.20.0 (IBM Corp., Armonk, NY, USA). Results: Of the 112 patients, 39% had HS, 54% had IS and 7% had TIA. A total of 29% of patients had elevated CATS/ METS. Elevated levels of CATS/METS were noted in 41% and 25% of HS and IS patients, respectively (p=0.53). Median norepinephrine, epinephrine and metanephrine levels in HS were significantly higher than IS (p< 0.05). Systolic blood pressure was higher in those who had elevated CATS/ METS (p=0.04). Only for two patients with elevated CATS/METS repeat testing was performed. Age, diastolic blood pressure and the time of sample collection in relation to the presentation, for CATS/METS were not significantly different between groups that had elevated levels of CATS/ METS versus those who did not. Conclusion: We noted that CATS/METS were elevated in one-third of patients, especially in patients with high systolic blood pressure. Increase in CATS/METS should be appropriately followed up with repeat testing. Since false elevation in CATS/METS has been reported in cerebrovascular disease, screening for phaeochromocytoma is best deferred for a month.

The clinical genetics of phaeochromocytoma and paraganglioma

ABSTRACT Phaeochromocytoma and paraganglioma are rare catecholamine-producing tumours, recognised to have one of the richest hereditary backgrounds of all neoplasms, with germline mutations seen in approximately 30% of patients. They can be a part of genetic syndromes such as MEN 2 or Neurofibromatosis type 1, or can be found as apparently sporadic tumours. Germline mutations are almost always found in syndromic patients. Nonetheless, apparently sporadic phaeochromocytoma too show high germline mutation rates. Early detection of a genetic mutation can lead to early diagnosis of further tumours via surveillance, early treatment and better prognosis. Apart from this, the genetic profile has important relevance for tumour location and biochemical profile, and can be a useful predictor of future tumour behaviour. It also enables family screening and surveillance. Moreover, recent studies have demonstrated significant driver somatic mutations in up to 75% of all tumours. Arch Endocrinol Metab. 2017;61(5):490-500

Manifestaciones inusuales del feocromocitoma: Reporte de caso y revisión de la literatura / Unusual manifestations of phaeochromocytoma: A case report and a review of the literature

El feocromocitoma es un tumor de baja prevalencia que se origina en las células cromafines de la médula de las glándulas suprarrenales. Estos tumores como el tejido simpático normal se originan del neuroectodermo. La tríada clásica de presentación clínica es: hipertensión que puede ser persistente, paroxística o fluctuante, cefalea grave pulsátil acompañada de náuseas y/o vómito y palpitaciones con taquicardia o bradicardia refleja; pero también se pueden presentar un gran número de síntomas debido al exceso de catecolaminas plasmáticas, llegando incluso a producir un síndrome coronario agudo. Su diagnóstico se realiza por medio de la clínica (para la cual se requiere un alto grado de sospecha), el laboratorio y la imagenología. El tratamiento de elección es la resección quirúrgica del tumor por laparoscopia o cirugía abierta.

A phaeochromocytoma is a tumour of low prevalence that originates in the chromaffin cells of the medulla of the adrenal glands. These tumours, like normal sympathetic tissue, originate from neuroectoderm. The classic triad of clinical findings are: hypertension that can be persistent, paroxysmal or fluctuating, severe throbbing headache accompanied by nausea and/or vomiting, and palpitations with tachycardia or reflex bradycardia. It can also present with a myriad of symptoms due to the excess of plasma catecholamines, even producing an acute coronary syndrome. Diagnosis is made through the clinical (for which requires a high degree of suspicion), laboratory, and imaging findings. The treatment is surgical resection of the tumour by laparoscopy or open surgery.

Phaeochromocytoma presenting with pseudo-intestinal obstruction and lactic acidosis

Phaeochromocytomas are rare neuroendocrine tumours with variable clinical signs and symptoms. Hypertension, tachycardia, sweating and headaches are cardinal manifestations. Although nausea and abdominal pain are the more common gastrointestinal features, rare gastrointestinal spectrums have been reported that can mimic abdominal emergencies. Metabolic effects of hypercatecholaminaemia are vast and one such rare presentation is lactic acidosis. We describe a case of phaeochromocytoma presenting with both intestinal pseudo-obstruction as well as lactic acidosis. This case report highlights the importance of having a high index of suspicion for and early recognition of the gastrointestinal and metabolic manifestations of phaeochromocytomas.

An Unusual Cause of an Uncommon Condition: Pulmonary Vein Stenosis.

Pulmonary vein stenosis in adults is historically a rare condition, but is becoming a recognised complication, albeit an uncommon one, of radiofrequency ablation around the pulmonary veins for treatment of atrial fibrillation. It may also be due to infiltrating mediastinal processes such as neoplasm or sarcoidosis. In this case report, a 55-year old man underwent resection of a mediastinal phaeochromocytoma involving the left atrial wall and the right inferior pulmonary vein. One year later he subsequently presented with increasing dyspnoea and atypical chest pain. Transthoracic echocardiogram showed severe pulmonary hypertension, right ventricular dilatation and dysfunction. Transesophageal echocardiogram demonstrated severe bilateral pulmonary vein stenosis with peak/mean gradients across the left pulmonary veins of about 25/20mmHg. The diagnosis was also confirmed on CT pulmonary angiography with 3D reconstruction. Open pulmonary vein stenting was planned but unfortunately the patient died suddenly before the procedure. Pulmonary vein stenosis is an uncommon but serious condition and may present with signs and symptoms indistinguishable from other conditions and may easily be missed. Clinicians should have a high index of suspicion when patients present with unexplained respiratory symptoms, especially in the context of catheter ablation or mediastinal processes such as neoplasm. Transesophageal echocardiography played an indispensible part in the correct diagnosis in our patient.

The role of urinary fractionated metanephrines in the diagnosis of phaeochromocytoma.

Background & objectives: Plasma and urinary metanephrines are used as screening tests for the diagnosis of phaeochromocytoma. The recommended cut-off levels are not standardized. This study was conducted to identify a cut-off level for 24 h urinary fractionated metanephrines viz. metanephrine (uMN) and normetanephrine (uNMN) using enzyme immunoassay for the diagnosis of phaeochromocytoma. Methods: Consecutive patients suspected to have phaeochromocytoma were included in the study. uMN and uNMN in 24 h urinary sample were measured using a commercial ELISA kit. Results: Overall, 72 patients were included over a period of 18 months. Twenty patients had histopathologically confirmed phaeochromocytoma and in 52 patients phaeochromocytoma was ruled out. Using the upper limit of normal stated by the assay manufacturer as the cut-off, uMN >350 μg/day had a low sensitivity and uNMN >600 μg/day had a poor specificity. By increasing the cut-off value of uNMN to twice the upper limit, specificity increased significantly without much loss in sensitivity. Combining uMN and uNMN using a cut-off twice the upper limit improved the diagnostic performance - sensitivity (95%); specificity (92.3%); positive predictive value (PPV - 82.6%); negative predictive value (NPV - 98%). In subsets of patients with a variable pretest probability for phaeochromocytoma, the PPV correlates well with the occurred of these tumors decreased, while the NPV remained at 100 per cent. Interpretation & conclusions: ELISA is a simple and reliable method for measuring uMN and uNMN. The test has a good NPV and can be used as an initial screening test for ruling out phaeochromocytoma. Each hospital will have to define the cut-off value for the assay being used, choosing a proper control population.

The predictive value of urinary vanillylmandelic acid testing in the diagnosis of phaeochromocytoma at the University Hospital of the West Indies / El valor predictivo de la prueba del ácido vanilmandélico en orina para el diagnóstico de la feocromositoma en el Hospital Universitario de West Indies

OBJECTIVE: To investigate the positive predictive value (PPV) of urinary vanillylmandelic acid (VMA) testing in the diagnosis of phaeochromocytoma and to describe the features associated with phaeo chromocytoma at the University Hospital of the West Indies (UHWI). SUBJECTS AND METHODS: There were 551 VMA tests performed from January 2003 to June 2009 and 122 tests in 85 patients were elevated (ie > 35 µmol/24 hr). The study patients were categorized as: (i) 'surgical' (5 patients who underwent surgery) or (ii) 'non-surgical' (remaining 80 patients). Forty medical charts (out of 85) were reviewed using a standardized data extraction form. RESULTS: The median age for patients in the non-surgical group (with charts reviewed, n = 35) was 36 years (range 9-70) and the median VMA was 43 µmol/24 hr (IQR 38-51). Of these patients, 83% had one or no symptom typical of phaeochromocytoma. In the surgical group the median VMA was 58 µmol/24 hr (IQR 44-101); phaeochromocytoma was confirmed histologically in 3 patients, all of whom had several symptoms typical of catecholamine excess. VMA testing had a PPV of 8%, specificity of 79% and sensitivity of 100%. CONCLUSIONS: VMA testing at UHWI has poor specificity and high sensitivity. These results contrast with international data showing that VMA testing is poorly sensitive but highly specific. The use of assays with higher specificity (egplasma or urinary metanephrines) may represent a more cost-effective approach to biochemical screening at UHWI.

OBJETIVO: Investigar el valor predictivo positivo (VPP) de las pruebas del ácido vanilmandélico urinario (VMA) en el diagnóstico de la feocromositoma y describir las características asociadas con la feocromositoma en el Hospital de la Universidad de West Indies (HUWI). SUJETOS Y MÉTODOS: Se realizaron unas 551 pruebas de VMA de enero de 2003 a junio de 2009, y 122 de las pruebas en 85 pacientes tuvieron resultados elevados (ie > 35 µmol/24 hr). Los pacientes del estudio fueron clasificados como: (i) "quirúrgicos" (5 pacientes que se sometieron a cirugía) ó (ii) "no quirúrgicos" (los 80 pacientes restantes). Se revisaron cuarenta historias clínicas (de 85) mediante un formulario estandarizado de extracción de datos. RESULTADOS: El promedio de edad de los pacientes en el grupo no quirúrgico (con historias clínicas, n = 35) fue de 36 años (rango 9-70) y la mediana VMA fue 43 µmol/24 h (IQR 38-51). De estos pacientes, 83% tenían uno o ningún síntoma típico de la feocromositoma. En el grupo quirúrgico la mediana VMA fue 58 µmol/24 h (IQR 44-101). La feocromositoma fue confirmada histológicamente en 3 pacientes, cada uno de los cuales presentó síntomas típicos de exceso de catecolaminas. Las pruebas de VMA tuvieron un VPP de 8%, una especificidad de 79%, y una sensibilidad de 100%. CONCLUSIONES: Las pruebas de VMA en HUWI poseen pobre especificidad y alta sensibilidad. Estos resultados contrastan con los datos internacionales que muestran que la prueba de VMA es pobremente sensible pero altamente específica. El uso de ensayos con mayor especificidad (por ejemplo, metanefrinas plasmáticas o urinarias) puede representar un método costo-efectivo a la hora de realizar el pesquisaje bioquímico en HUWI.

Expression of human telomerase reverse transcriptase hTERT,Ki-67 and p27~(kip1) in pheochromocytoma and their significance / 中国实用内科杂志

Objective To investigate the expression of human telomerase reverse transcriptase(hTERT),Ki-67 and p27~(kip1) in pheochromocytoma and paraganglioma,and to evaluate whether the expression of hTERT,Ki-67 and p27~(kip1) could serve as diagnostic markers for predicting the biological behaviour of these tumours.Methods Expression of hTERT,Ki-67 and p27~(kip1) was determined by immunohistochemistry in 45 pheochromocytomas/paragangliomas(31 benign,7 suspected malignant and 7 malignant)and 9 normal adrenal medulla samples.Results The hTERT was expressed in 5/7 malignant tumors,5/7 suspected malignant tumours and 3/31 benign tumours.Malignant and suspected malignant tumors expressed more hTERT(P

Expressions and significance of human telomerase reverse transcriptase mRNA and protein in pheochromocytoma / 中华内分泌代谢杂志

Objective To investigate the expressions of human telomerase reverse transcriptase(hTERT) mRNA and protein in pheochromocytoma and paraganglioma and their significance as diagnostic markers in predicting the biological behaviour of these tumours.Methods Expression of hTERT mRNA was determined by in situ hybridization in 45 pheochromocytomas/paragangliomas(31 benign,7 suspected malignant and 7 malignant) and 9 normal adrenal medulla samples,hTERT protein was determined by immunohistoebemistry.Results hTERT mRNA was expressed in 5/7 malignant turnouts and 5/7 suspected malignant tumours as compared with 3/31 benign tumours(P